The AALL1331 trial compared blinatumomab to chemotherapy as consolidation therapy after re-induction in pediatric patients with first relapse B-cell acute lymphoblastic leukemia. The open-label, randomized controlled trial found that blinatumomab significantly improved disease-free survival compared to chemotherapy, with 3-year disease-free survival rates of 45% for blinatumomab versus 27% for chemotherapy. Blinatumomab was generally well-tolerated though adverse events included cytokine release syndrome and neurotoxicity. The results support using blinatumomab as consolidation therapy to bridge pediatric B-ALL patients to hematopoietic stem cell transplant.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
This study examined the association between statin and beta-blocker (BB) use and outcomes in 130 patients diagnosed with both head and neck cancer and diabetes mellitus. The results showed that use of lipophilic statins and selective BBs was associated with improved overall survival and disease-free survival. However, the small sample sizes of patients using hydrophilic statins and non-selective BBs may have biased these results. The study was limited by its inability to determine medication duration but suggests longer use prior to cancer diagnosis.
The document summarizes the potential of T-cell engaging bispecific antibodies (TCEs) for the treatment of solid tumors. It discusses how TCEs directly link T-cells to tumor cells expressing a target antigen like DLL3, which is expressed in over 80% of small cell lung cancer (SCLC) tumors. The document outlines ongoing clinical trials of TCEs targeting DLL3 for the treatment of SCLC and neuroendocrine tumors.
The document discusses the development of chimeric antigen receptor (CAR) gene therapy for cancer treatment. It describes how early T-cell receptor modification efforts were unsuccessful due to immune rejection, leading to the creation of entirely new CAR receptors. CAR therapy generates antibodies to target antigens on cancer cells. The CAR is constructed through multiple steps and generations have improved effects. CAR therapy activates T-cells to attack cancer cells and has shown promising results in clinical trials.
bcell lymphomas national comprehensive cancer networkArielArdinda1
The document summarizes updates made in Version 5.2022 of the NCCN Guidelines for B-Cell Lymphomas from Version 4.2022, including:
- Adding lisocabtagene maraleucel as a category 2A recommendation for second-line therapy of diffuse large B-cell lymphoma in certain situations.
- Global changes such as updated treatment regimens and references throughout the guidelines.
- Revisions to diagnostic testing recommendations and certain treatment options.
Letter: Is the Stupp Protocol an expensive and unsustainable standard of care...Ahmad Ozair
Glioblastoma multiforme (GBM) is the most common and aggressive primary adult brain neoplasm with an age-adjusted incidence rate of 3.22 per 100 000 individuals and a 5-yr survival rate of 6.8%.1 In 2005, Stupp and colleagues proposed maximal safe resection, concomitant temozolomide (TMZ) with radiotherapy, and adjuvant TMZ as the optimal treatment. Implementation of the Stupp protocol in high-income countries (HICs) has resulted in increased survival compared to previous regimens. With little-to-no literature on the management and outcomes of patients with GBM in low- and middle-income countries (LMICs), it is unclear whether the Stupp protocol is being adopted or whether it is, or ever can be, the optimal strategy in LMICs...
Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multi...CristinaGeorgianaZah
authors:
Christina Peters, MD1; Jean-Hugues Dalle, MD, PhD2; Franco Locatelli, MD, PhD3; Ulrike Poetschger, PhD4; Petr Sedlacek, MD5;
Jochen Buechner, MD, PhD6; Peter J. Shaw, MD7; Raquel Staciuk, MD8; Marianne Ifversen, MD, PhD9; Herbert Pichler, MD1;
Kim Vettenranta, MD, PhD10; Peter Svec, MD, PhD11; Olga Aleinikova, MD, PhD12; Jerry Stein, MD13; Tayfun Gu¨ngo¨ r, MD14;
Jacek Toporski, MD15; Tony H. Truong, MD, MPH16; Cristina Diaz-de-Heredia, MD17; Marc Bierings, MD, PhD18; Hany Ariffin, MD, PhD19;
Mohammed Essa, MD20; Birgit Burkhardt, MD, PhD21; Kirk Schultz, MD22; Roland Meisel, MD23; Arjan Lankester, MD, PhD24;
Marc Ansari, MD25; and Martin Schrappe, MD, PhD,26 on behalf of the IBFM Study Group; Arend von Stackelberg, MD,27 on behalf of the
IntReALL Study Group; Adriana Balduzzi, MD,28 on behalf of the I-BFM SCT Study Group; Selim Corbacioglu, MD,29 on behalf of the
EBMT Paediatric Diseases Working Party; and Peter Bader, MD30
diffuse large B cell lymphoma recent molecular classification
molecular classification and their time frame with references
Recent advantages of DLBCL and thier implication in therapy
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
This study examined the association between statin and beta-blocker (BB) use and outcomes in 130 patients diagnosed with both head and neck cancer and diabetes mellitus. The results showed that use of lipophilic statins and selective BBs was associated with improved overall survival and disease-free survival. However, the small sample sizes of patients using hydrophilic statins and non-selective BBs may have biased these results. The study was limited by its inability to determine medication duration but suggests longer use prior to cancer diagnosis.
The document summarizes the potential of T-cell engaging bispecific antibodies (TCEs) for the treatment of solid tumors. It discusses how TCEs directly link T-cells to tumor cells expressing a target antigen like DLL3, which is expressed in over 80% of small cell lung cancer (SCLC) tumors. The document outlines ongoing clinical trials of TCEs targeting DLL3 for the treatment of SCLC and neuroendocrine tumors.
The document discusses the development of chimeric antigen receptor (CAR) gene therapy for cancer treatment. It describes how early T-cell receptor modification efforts were unsuccessful due to immune rejection, leading to the creation of entirely new CAR receptors. CAR therapy generates antibodies to target antigens on cancer cells. The CAR is constructed through multiple steps and generations have improved effects. CAR therapy activates T-cells to attack cancer cells and has shown promising results in clinical trials.
bcell lymphomas national comprehensive cancer networkArielArdinda1
The document summarizes updates made in Version 5.2022 of the NCCN Guidelines for B-Cell Lymphomas from Version 4.2022, including:
- Adding lisocabtagene maraleucel as a category 2A recommendation for second-line therapy of diffuse large B-cell lymphoma in certain situations.
- Global changes such as updated treatment regimens and references throughout the guidelines.
- Revisions to diagnostic testing recommendations and certain treatment options.
Letter: Is the Stupp Protocol an expensive and unsustainable standard of care...Ahmad Ozair
Glioblastoma multiforme (GBM) is the most common and aggressive primary adult brain neoplasm with an age-adjusted incidence rate of 3.22 per 100 000 individuals and a 5-yr survival rate of 6.8%.1 In 2005, Stupp and colleagues proposed maximal safe resection, concomitant temozolomide (TMZ) with radiotherapy, and adjuvant TMZ as the optimal treatment. Implementation of the Stupp protocol in high-income countries (HICs) has resulted in increased survival compared to previous regimens. With little-to-no literature on the management and outcomes of patients with GBM in low- and middle-income countries (LMICs), it is unclear whether the Stupp protocol is being adopted or whether it is, or ever can be, the optimal strategy in LMICs...
Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multi...CristinaGeorgianaZah
authors:
Christina Peters, MD1; Jean-Hugues Dalle, MD, PhD2; Franco Locatelli, MD, PhD3; Ulrike Poetschger, PhD4; Petr Sedlacek, MD5;
Jochen Buechner, MD, PhD6; Peter J. Shaw, MD7; Raquel Staciuk, MD8; Marianne Ifversen, MD, PhD9; Herbert Pichler, MD1;
Kim Vettenranta, MD, PhD10; Peter Svec, MD, PhD11; Olga Aleinikova, MD, PhD12; Jerry Stein, MD13; Tayfun Gu¨ngo¨ r, MD14;
Jacek Toporski, MD15; Tony H. Truong, MD, MPH16; Cristina Diaz-de-Heredia, MD17; Marc Bierings, MD, PhD18; Hany Ariffin, MD, PhD19;
Mohammed Essa, MD20; Birgit Burkhardt, MD, PhD21; Kirk Schultz, MD22; Roland Meisel, MD23; Arjan Lankester, MD, PhD24;
Marc Ansari, MD25; and Martin Schrappe, MD, PhD,26 on behalf of the IBFM Study Group; Arend von Stackelberg, MD,27 on behalf of the
IntReALL Study Group; Adriana Balduzzi, MD,28 on behalf of the I-BFM SCT Study Group; Selim Corbacioglu, MD,29 on behalf of the
EBMT Paediatric Diseases Working Party; and Peter Bader, MD30
diffuse large B cell lymphoma recent molecular classification
molecular classification and their time frame with references
Recent advantages of DLBCL and thier implication in therapy
This document provides the updated NCCN Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (ALL). It summarizes changes made in Version 3.2023, including adding a footnote specifying that a FDA-approved biosimilar is an appropriate substitute for tocilizumab for supportive care. It also lists other modifications made in Version 2.2023, such as updates to consolidation therapy regimens, footnotes, and response criteria. The guidelines are reviewed and updated regularly by the NCCN ALL Panel to incorporate the latest evidence and clinical expertise for the treatment of ALL.
Luciano J. Costa, MD, PhD, prepared useful Practice Aids pertaining to multiple myeloma for this CME activity titled "Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact of Novel Platforms and Agent Classes Across the Spectrum of Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Dypn7b. CME credit will be available until March 12, 2020.
This document provides an overview of primary sclerosing cholangitis (PSC), including:
- PSC affects less than 200,000 individuals in the US with higher rates in Northern Europe.
- The cause is unknown but likely involves genetic and immune factors. It is characterized by inflammation and fibrosis of the bile ducts.
- PSC often occurs with inflammatory bowel disease and increases the risk of cholangiocarcinoma and colon cancer.
- Diagnosis involves blood tests, imaging like MRCP, and may involve biopsy.
- There is no curative treatment but ursodeoxycholic acid may help. Liver transplantation is considered for advanced disease.
- Areas of research
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
The document provides guidelines for the treatment of cutaneous melanoma. It was created by the National Comprehensive Cancer Network (NCCN) and outlines recommendations for evaluating and managing melanoma based on the stage of disease. The guidelines are reviewed regularly and updated based on the latest evidence and consensus among experts. They provide information on diagnosis, pathology, imaging, surgery, radiation, systemic therapies, management of toxicities, follow-up care, and special considerations for different stages of melanoma from 0 to IV.
Awareness about Liver Cancer in Biotechnology Students_Crimson PublishersCrimsonpublishersCancer
The document discusses a study assessing awareness of liver cancer among biotechnology students. A questionnaire was developed to evaluate students' knowledge of the etiology, transmission, treatment and personal experience with liver cancer. The results showed that the postgraduate students demonstrated a high level of awareness about liver cancer, its causes as either viral, genetic or metabolic disease, and potential treatments like medicines or surgery. The study concluded that the students displayed a comprehensive understanding of liver cancer.
This document presents the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for B-Cell Lymphomas. It describes updates made in versions 2.2023 and 1.2023 of the guidelines, including revisions to recommendations for mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and extranodal marginal zone lymphoma. New systemic therapies were added for certain disease subtypes and clinical scenarios. Terminology and classifications were updated based on recent international consensus standards.
This document provides information from the GrassrootsHealth organization regarding vitamin D research and recommendations. It includes the following:
- A summary of several studies showing reductions in disease incidence as vitamin D serum levels increase from 25 ng/ml to higher levels such as 40-60 ng/ml. Diseases such as cancer, diabetes, fractures, and multiple sclerosis showed reductions.
- Charts analyzing data from over 7,000 participants in the GrassrootsHealth D*action project, showing a wide range of serum levels for any given supplemental vitamin D intake amount. Intakes of 4,000 IU/day resulted in serum levels from 10-150 ng/ml.
- Analysis suggesting supplemental intakes of 9,
Precision Medicine in Oncology InformaticsWarren Kibbe
This document summarizes a presentation on precision medicine in oncology from an informatics perspective. It discusses the goals of precision oncology to target cancer treatments based on a patient's individual tumor characteristics. Major initiatives are described, including the NCI-MATCH trial which assigns cancer therapies based on a tumor's molecular abnormalities. The presentation outlines efforts through the Precision Medicine Initiative to expand genomic cancer trials, understand and overcome resistance to therapies through additional tumor profiling and preclinical models, and establish an integrated national cancer database.
Michael Wang, MD, and Michael J. Keating, MB, BS, prepared useful Practice Aids pertaining to B-cell malignancies for this CME activity titled "Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2zChqfa. CME credit will be available until October 11, 2019.
This document provides guidelines for the treatment of hepatobiliary cancers from the National Comprehensive Cancer Network (NCCN). It was last updated on October 14, 2022. The guidelines include the latest recommendations for screening, diagnosing, and treating hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. New recommendations include durvalumab plus chemotherapy as a preferred regimen for unresectable biliary tract cancer, and selpercatinib for RET fusion-positive hepatobiliary tumors.
This document discusses approaches to personalized cancer therapy. It describes precision medicine as targeting patient subgroups rather than individuals based on genetic markers. The right target, drug or drug combinations, and patient are key to accomplish this. An example is given of a novel CDK4/6 inhibitor being tested in breast cancer subgroups. Another example discusses an anti-CD22 antibody-drug conjugate showing promise for certain lymphomas. The document also outlines molecular subtypes in lung cancer and how targeted therapies like crizotinib have been effective in subsets of patients with genetic alterations like ALK rearrangement.
This document provides information from GrassrootsHealth on vitamin D research and dosing recommendations. It includes the following:
- A summary of studies showing reductions in disease incidence as vitamin D levels increase from 25 to over 60 ng/ml. Many diseases such as cancer, diabetes and heart disease showed reductions of over 30% at levels of 40 ng/ml or higher.
- Charts showing the wide range of serum vitamin D levels achieved at different daily supplemental intake amounts, based on data from over 7,000 participants. Intakes of 4000 IU/day resulted in levels from 20-120 ng/ml, demonstrating individual variability.
- Recommendations that total daily vitamin D intake of around 12,000 IU
The document summarizes updates made in Version 2.2022 of the NCCN Guidelines for Breast Cancer from Version 1.2022, including:
- Recommendations for lobular carcinoma in situ were removed and can now be found in the NCCN Guidelines for Breast Cancer Screening and Diagnosis.
- The bullet on sequence of radiation therapy with systemic therapy on page BINV-I was modified for clarification.
- The footnote on page BINV-K was modified for clarification on adjuvant abemaciclib treatment.
Predictors of imatinib failure in cml by prof. abinyaKesho Conference
This study examined predictors of treatment failure in chronic myeloid leukemia (CML) patients receiving imatinib therapy at a hospital in Nairobi, Kenya. The study found that 20.9% of 206 CML patients treated with imatinib experienced hematologic treatment failure, with most having secondary rather than primary failure. Missed imatinib doses, higher BCR-ABL levels at diagnosis, and a longer duration between CML diagnosis and starting imatinib therapy were associated with treatment failure. On logistic regression, only a prolonged duration between diagnosis and starting imatinib was an independent predictor of failure. The study aims to help identify patients at higher risk of imatinib treatment failure so they can be considered for
This document provides updates to the 2022 National Comprehensive Cancer Network (NCCN) clinical practice guidelines for pancreatic adenocarcinoma. Key updates include revising terminology related to genetic testing and molecular profiling, emphasizing multidisciplinary review for diagnosis and treatment planning, and recommending genetic testing for inherited mutations and tumor molecular profiling to identify potentially targetable biomarkers. The guidelines provide evidence-based recommendations for diagnosis, staging, treatment and surveillance of pancreatic adenocarcinoma.
This document discusses the potential of biomarkers in improving diagnosis, prognosis, and treatment of hematological malignancies. It summarizes that biomarkers offer hope for early detection, distinguishing aggressive from indolent disease, and tracking disease progression. Biomarkers could allow for patient-specific treatment selection to improve outcomes with lower drug doses. The document reviews recent advances in applying biomarkers to multiple myeloma, lymphomas including diffuse large B-cell lymphoma, and acute myeloid leukemia. Integration of clinical, genetic, and molecular biomarker data may help translate these advances into better patient outcomes.
Using primary care databases to evaluate drug benefits and harms: are the res...David Springate
Databases of electronic medical records and in particular primary care databases (PCDs) are increasingly used in research. The largest PCDs contain full data on all primary care consultations by millions of patients over two or more decades. They provide a means for investigating important healthcare questions which cannot be practically addressed in a Randomised Controlled Trial. However, concerns remain about the validity of studies based on data from PCDs. Most work around validity has attempted to confirm individual data values within a dataset. We take a different approach and instead replicate published PCD studies in a second, independent, PCD. Agreement of results then implies that the conclusions drawn are independent of the data source (though this doesn’t rule out that such as confounding by indication are commonly influencing both).
We replicated two previous PCD studies using the Clinical Practice Research Datalink (CPRD). The first was a retrospective cohort study of the effect of Beta-blocker therapy on survival in cancer patients using DIN-LINK. The second was a nested case-control analysis of the effects of Statins on mortality of patients with ischaemic heart disease using QRESEARCH.
Our analyses produced several important quantitative differences compared to the original studies, altering conclusions. These could not be fully explained by either demographic differences in the patient samples or structural differences between the datasets. Our study highlights both the caution that needs to be applied when assessing the findings from analysis of just a single database and the difficulties in performing replications of existing PCD studies.
Coronary artery disease remains the leading cause of death in the US. Acute coronary syndromes are caused by a sudden reduction in coronary blood flow due to atherosclerosis. There are three presentations of ACS: unstable angina, NSTEMI, and STEMI. Treatment involves stabilizing the patient, risk stratification, and determining reperfusion strategy which may involve fibrinolysis, PCI, or CABG. Long term management focuses on preventative therapies including antiplatelets, statins, beta blockers, ACE inhibitors, and other secondary prevention medications.
This document summarizes the background, objectives, methods, and endpoints of the MENDS2 trial, a randomized controlled trial comparing dexmedetomidine to propofol for sedation in mechanically ventilated adults with sepsis. The trial aims to test whether dexmedetomidine results in better short-term outcomes, such as fewer days of delirium or coma and more ventilator-free days, and long-term outcomes like survival and cognition at 6 months compared to propofol. The trial plans to enroll approximately 420 patients and randomize them 1:1 to receive either dexmedetomidine or propofol infusion titrated to light sedation. The primary outcome is the number of days alive
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This document provides the updated NCCN Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (ALL). It summarizes changes made in Version 3.2023, including adding a footnote specifying that a FDA-approved biosimilar is an appropriate substitute for tocilizumab for supportive care. It also lists other modifications made in Version 2.2023, such as updates to consolidation therapy regimens, footnotes, and response criteria. The guidelines are reviewed and updated regularly by the NCCN ALL Panel to incorporate the latest evidence and clinical expertise for the treatment of ALL.
Luciano J. Costa, MD, PhD, prepared useful Practice Aids pertaining to multiple myeloma for this CME activity titled "Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact of Novel Platforms and Agent Classes Across the Spectrum of Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Dypn7b. CME credit will be available until March 12, 2020.
This document provides an overview of primary sclerosing cholangitis (PSC), including:
- PSC affects less than 200,000 individuals in the US with higher rates in Northern Europe.
- The cause is unknown but likely involves genetic and immune factors. It is characterized by inflammation and fibrosis of the bile ducts.
- PSC often occurs with inflammatory bowel disease and increases the risk of cholangiocarcinoma and colon cancer.
- Diagnosis involves blood tests, imaging like MRCP, and may involve biopsy.
- There is no curative treatment but ursodeoxycholic acid may help. Liver transplantation is considered for advanced disease.
- Areas of research
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
The document provides guidelines for the treatment of cutaneous melanoma. It was created by the National Comprehensive Cancer Network (NCCN) and outlines recommendations for evaluating and managing melanoma based on the stage of disease. The guidelines are reviewed regularly and updated based on the latest evidence and consensus among experts. They provide information on diagnosis, pathology, imaging, surgery, radiation, systemic therapies, management of toxicities, follow-up care, and special considerations for different stages of melanoma from 0 to IV.
Awareness about Liver Cancer in Biotechnology Students_Crimson PublishersCrimsonpublishersCancer
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This document presents the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for B-Cell Lymphomas. It describes updates made in versions 2.2023 and 1.2023 of the guidelines, including revisions to recommendations for mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and extranodal marginal zone lymphoma. New systemic therapies were added for certain disease subtypes and clinical scenarios. Terminology and classifications were updated based on recent international consensus standards.
This document provides information from the GrassrootsHealth organization regarding vitamin D research and recommendations. It includes the following:
- A summary of several studies showing reductions in disease incidence as vitamin D serum levels increase from 25 ng/ml to higher levels such as 40-60 ng/ml. Diseases such as cancer, diabetes, fractures, and multiple sclerosis showed reductions.
- Charts analyzing data from over 7,000 participants in the GrassrootsHealth D*action project, showing a wide range of serum levels for any given supplemental vitamin D intake amount. Intakes of 4,000 IU/day resulted in serum levels from 10-150 ng/ml.
- Analysis suggesting supplemental intakes of 9,
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This document summarizes a presentation on precision medicine in oncology from an informatics perspective. It discusses the goals of precision oncology to target cancer treatments based on a patient's individual tumor characteristics. Major initiatives are described, including the NCI-MATCH trial which assigns cancer therapies based on a tumor's molecular abnormalities. The presentation outlines efforts through the Precision Medicine Initiative to expand genomic cancer trials, understand and overcome resistance to therapies through additional tumor profiling and preclinical models, and establish an integrated national cancer database.
Michael Wang, MD, and Michael J. Keating, MB, BS, prepared useful Practice Aids pertaining to B-cell malignancies for this CME activity titled "Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2zChqfa. CME credit will be available until October 11, 2019.
This document provides guidelines for the treatment of hepatobiliary cancers from the National Comprehensive Cancer Network (NCCN). It was last updated on October 14, 2022. The guidelines include the latest recommendations for screening, diagnosing, and treating hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. New recommendations include durvalumab plus chemotherapy as a preferred regimen for unresectable biliary tract cancer, and selpercatinib for RET fusion-positive hepatobiliary tumors.
This document discusses approaches to personalized cancer therapy. It describes precision medicine as targeting patient subgroups rather than individuals based on genetic markers. The right target, drug or drug combinations, and patient are key to accomplish this. An example is given of a novel CDK4/6 inhibitor being tested in breast cancer subgroups. Another example discusses an anti-CD22 antibody-drug conjugate showing promise for certain lymphomas. The document also outlines molecular subtypes in lung cancer and how targeted therapies like crizotinib have been effective in subsets of patients with genetic alterations like ALK rearrangement.
This document provides information from GrassrootsHealth on vitamin D research and dosing recommendations. It includes the following:
- A summary of studies showing reductions in disease incidence as vitamin D levels increase from 25 to over 60 ng/ml. Many diseases such as cancer, diabetes and heart disease showed reductions of over 30% at levels of 40 ng/ml or higher.
- Charts showing the wide range of serum vitamin D levels achieved at different daily supplemental intake amounts, based on data from over 7,000 participants. Intakes of 4000 IU/day resulted in levels from 20-120 ng/ml, demonstrating individual variability.
- Recommendations that total daily vitamin D intake of around 12,000 IU
The document summarizes updates made in Version 2.2022 of the NCCN Guidelines for Breast Cancer from Version 1.2022, including:
- Recommendations for lobular carcinoma in situ were removed and can now be found in the NCCN Guidelines for Breast Cancer Screening and Diagnosis.
- The bullet on sequence of radiation therapy with systemic therapy on page BINV-I was modified for clarification.
- The footnote on page BINV-K was modified for clarification on adjuvant abemaciclib treatment.
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This document provides updates to the 2022 National Comprehensive Cancer Network (NCCN) clinical practice guidelines for pancreatic adenocarcinoma. Key updates include revising terminology related to genetic testing and molecular profiling, emphasizing multidisciplinary review for diagnosis and treatment planning, and recommending genetic testing for inherited mutations and tumor molecular profiling to identify potentially targetable biomarkers. The guidelines provide evidence-based recommendations for diagnosis, staging, treatment and surveillance of pancreatic adenocarcinoma.
This document discusses the potential of biomarkers in improving diagnosis, prognosis, and treatment of hematological malignancies. It summarizes that biomarkers offer hope for early detection, distinguishing aggressive from indolent disease, and tracking disease progression. Biomarkers could allow for patient-specific treatment selection to improve outcomes with lower drug doses. The document reviews recent advances in applying biomarkers to multiple myeloma, lymphomas including diffuse large B-cell lymphoma, and acute myeloid leukemia. Integration of clinical, genetic, and molecular biomarker data may help translate these advances into better patient outcomes.
Using primary care databases to evaluate drug benefits and harms: are the res...David Springate
Databases of electronic medical records and in particular primary care databases (PCDs) are increasingly used in research. The largest PCDs contain full data on all primary care consultations by millions of patients over two or more decades. They provide a means for investigating important healthcare questions which cannot be practically addressed in a Randomised Controlled Trial. However, concerns remain about the validity of studies based on data from PCDs. Most work around validity has attempted to confirm individual data values within a dataset. We take a different approach and instead replicate published PCD studies in a second, independent, PCD. Agreement of results then implies that the conclusions drawn are independent of the data source (though this doesn’t rule out that such as confounding by indication are commonly influencing both).
We replicated two previous PCD studies using the Clinical Practice Research Datalink (CPRD). The first was a retrospective cohort study of the effect of Beta-blocker therapy on survival in cancer patients using DIN-LINK. The second was a nested case-control analysis of the effects of Statins on mortality of patients with ischaemic heart disease using QRESEARCH.
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Seminar 2022 presentation final_ASANDLER.pptx
1. Blinatumomab as Bridge Therapy to
Transplant in Pediatric Patients with
First-Relapse B-Cell Acute
Lymphoblastic Leukemia
Anna Sandler, PharmD Candidate, 2023
Pharmacy Skills IX
April 14th, 2022
1
2. Introduction: B-cell Acute
Lymphoblastic Leukemia (B-ALL)
2
Growing field Pediatric literature Role for pharmacists
https://www.istockphoto.com/photos/oncology. Accessed March 30, 2022
John Hopkins Medicine. https://www.hopkinsmedicine.org/johns-hopkins-childrens-center/what-we-treat/specialties/oncology/. Accessed March 30, 2022
Statnews. https://www.statnews.com/2019/02/06/cancer-treatment-at-home-safe-effective/. Accessed March 30, 2022
3. Learning Objectives
Explain the epidemiology and pathophysiology of
relapsed B-ALL
Identify current treatment options for relapsed B-
ALL and their limitations
Evaluate literature to determine the role of
blinatumomab in relapsed B-ALL
Formulate a treatment plan for a patient case
3
4. Patient case
LP is a nine-year old female brought to the ED at 0310 after waking
up in the middle of the night, shivering and sweating. Her mother
notes a recent 10-pound weight loss. LP has a PMH of B-ALL and is
currently in remission. The oncologist reveals LP’s ALL has returned,
and LP is started on re-induction therapy for 4 weeks.
Current
Medications
Physical
Exam/Vitals
PMH
• B-ALL
• Dx 11/2019
• In remission
• Maintenance
chemotherapy
* for ~ 2 years
CBC (@ 0344)
03.16.2022 04.14.2022 Future?
• Weight: 29
kg
• Height:
132.1 cm
• Temp: 100.7
NCCN guidelines, https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1410, accessed
March 15, 2022
• ANC: 600[L]
• Blasts: 20%[H]
• WBC: 12
• Plt: 90[L]
4
5. Patient case-continued
Today, a bone marrow (BM) biopsy is obtained to evaluate LP’s status
after 4 weeks of re-induction treatment. LP’s oncologist recommends a
hematopoietic stem cell transplant (HSCT).
Bone Marrow
Biopsy (@ 0701)
03.16.2022 04.14.2022 Future?
• Flow
cytometry: (+)
CD19
• MRD > 0.1%
Lumbar
Puncture
• Negative for
CNS disease
Patient
Classification
• Isolated BM
B-ALL
• Early-relapse
• High-risk
5
6. Clinical Question
During rounds, LP’s oncologist turns to you and asks
whether she would be a good candidate for blinatumomab to
bridge her before transplant.
What would you recommend?
03.16.2022 04.14.2022 Future?
6
Re-induction HSCT
7. B-Cell Acute Lymphoblastic Leukemia
Background Brown et al. Locatelli et al. Conclusion
• Comprises 80-85%
of ALL
• Most common
childhood
cancer, > 25%
Belson M, et al. Environmental Health Perspectives. 2007;115(1):138-145. doi:10.1289/ehp.9023
CDC https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/key-statistics.html. Accessed
March 11, 2022.
Chang JH, et al. Pediatr Blood Cancer. 2021;68(S2). doi:10.1002/pbc.28371
7
Rate
per
100,000
persons
Year
Rate of new cases
Death Rate
8. Pathophysiology
Background Brown et al. Locatelli et al. Conclusion
• B-ALL: Unregulated growth
of B-cell lymphoBLASTs
• Immature cells
• Isolated to BM or outside-
extramedullary
• Relapse: Return of blasts after
treatment
American Society of Hematology (ASH)
https://imagebank.hematology.org/image/61569/ball-blasts-in-blood, accessed
March 11, 2022
National Cancer Institute https://www.cancer.gov/types/leukemia/patient/child-all-
treatment-pdq, accessed March 11, 2022
8
9. Diagnosis
Background Brown et al. Locatelli et al. Conclusion
Chang JH, et al. Pediatr Blood Cancer. 2021;68(S2). doi:10.1002/pbc.28371
Biopsy
Microscopy +
Flow cytometry
Detection of
blasts
Measurable residual disease (MRD): Remaining blasts after
treatment; Negative MRD < 0.01%
First dx: > 20% blasts
Relapse: Return of blasts
Remission: <5% blasts
9
10. Survival in relapsed B-ALL is poor
Background Brown et al. Locatelli et al. Conclusion
Nguyen K, Devidas M, Cheng SC, et al. Leukemia. 2008;22(12):2142-2150. doi:10.1038/leu.2008.251
• First-relapse
• 5-year survival
rate: 25-50%
• Non-relapsed
• 5-year survival
rate: 69.9%
20-25% of
Children still
relapse
10
11. Clinical Presentation
Background Brown et al. Locatelli et al. Conclusion
•Leukocytosis and Infection
•Thrombocytopenia
•Anemia
Myelosuppression
•Lymphadenopathy
•CNS effects
Metastasis
•Recurrent fevers and unexplained weight loss
•Bleeding
Feeling unwell
CMP
CBC
PT/PTT
Physical
Exam
Patient
History
Blackburn LM et al. Seminars in Oncology Nursing. 2019;35(6):150950. doi:10.1016/j.soncn.2019.150950
11
12. Background Brown et al. Locatelli et al. Conclusion
González Llano O. Medicina Universitaria. 2016;18(73):216-218. doi:10.1016/j.rmu.2016.07.006
Raetz EA, et al. Hematology Am Soc Hematol Educ Program. 2012;2012:129-136.
doi:10.1182/asheducation-2012.1.129 12
Achieve remission
Prevent relapses
Prolong survival
Treatment
Goals of
relapsed B-
ALL
13. Current Treatment of relapsed B-ALL
Background Brown et al. Locatelli et al. Conclusion
I.
•Re-induction
•Dexamethasone, vincristine, mitoxantrone, pegaspargase
II.
•Consolidation
•Dexamethasone, vincristine, MTX, pegaspargase,
cyclophosphamide, etoposide, cytarabine, leucovorin
III.
•HSCT
•Early, high-risk relapse
Hunger SP et al. Blood. 2020;136(16):1803-1812. doi:10.1182/blood.2019004043
Pulsipher MA, et al. Blood. 2015;125(22):3501-3508. doi:10.1182/blood-2014-12-615757 13
Goal: Remission (< 5% blasts)
Optimal candidates: Non-infected, (-) MRD
Blinatumomab?
14. Blinatumomab (BLINCYTO®)
Background Brown et al. Locatelli et al. Conclusion
• Anti-CD19/CD3
mAb
• Bispecific T-cell
engager (BiTE)
• Links T cells and
malignant B cells
• Directs cell lysis
Class/MOA Indications
• CD19 positive B-
ALL in first or
second complete
remission (CR) +
MRD ≥ 0.1%
14
BLINCYTO® (blinatumomab) Published online February 2022. Accessed March 12, 2022.
Springer.com.https://link.springer.com/article/10.1007/s40264-018-0760-1. Accessed March 12, 2022
15. Blinatumomab (BLINCYTO®)
Background Brown et al. Locatelli et al. Conclusion
PK
• Elimination half life:
• 2.04 +/- 1.35 hrs
• Metabolism
• Peptide
degradation
• Excretion:
• Urine (negligible)
ADRs BBW
• Edema
• Infusion-related
reactions
• Pancreatitis
• Lymphocytopenia
• 24/48 hr infusions
• Cytokine release
syndrome
• Fever
• Hypotension
• Neurological
toxicities
• Tremors
• Seizures
• Loss of
consciousness
Administration
15
BLINCYTO® (blinatumomab) for injection, for intravenous use full
prescribing information. Published online February 2022. Accessed
March 12, 2022.
16. Clinical Question: Place in Therapy
Background Brown et al. Locatelli et al. Conclusion
Oskarsson T, et al. Pediatr Blood Cancer. 2018;65(4):e26909. doi:10.1002/pbc.26909
Queudeville M et al. JCM. 2021;10(12):2544. doi:10.3390/jcm10122544Ind 16
Re-induction HSCT
17. Background Brown et al. Locatelli et al. Conclusion
Effect of Postreinduction Therapy
Consolidation With Blinatumomab vs.
Chemotherapy on Disease-Free Survival in
Children, Adolescents, and Young Adults with
First Relapse B-cell Acute Lymphoblastic
Leukemia
A Randomized Clinical Trial
Patrick A. Brown, MD; Lingyun Ji, PhD; Xinxin Xu, MS, et al. (2021)
Literature Review:
AALL1331 Trial
17
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
18. Background Brown et al. Locatelli et al. Conclusion
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669 18
•Compare the effect of post-reinduction blinatumomab to
chemotherapy on disease-free survival in high and
intermediate-risk first relapse B-ALL patients proceeding
to HSCT
•Funding: NIH, NCI, and St. Baldrick’s Foundation
Objective
•Open label, multi-center, phase III, randomized control
trial
Design
• Blinatumomab: Two 28-day infusion cycles with a 7-day
break in between
•15 mcg/m2/day
Intervention
19. Background Brown et al. Locatelli et al. Conclusion
•1-30 years of age
•First-relapse B-ALL
Inclusion Criteria
•Down Syndrome
•Ph+ ALL
•Previous transplant or blinatumomab therapy
Exclusion Criteria
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
19
20. Background Brown et al. Locatelli et al. Conclusion
Randomization
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
Randomization: Consolidation Treatment
Blinatumomab Chemotherapy
Risk stratification (MRD)
High and Intermediate relapse risk only
Re-induction chemotherapy*
Everyone
20
21. Background Brown et al. Locatelli et al. Conclusion
Randomization
High risk
Chemo
Blinatumomab
Intermediate
risk
Chemo
Blinatumomab
Randomization with stratification
1:1
21
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
22. Background Brown et al. Locatelli et al. Conclusion
Outcomes-Efficacy
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
45%
incidence
rate
110
pts/arm 85% power
63%
improvement
22
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
Outcome Description Statistical Test
Primary Disease-free survival (DFS):
Time from randomization to
treatment failure, relapse,
secondary malignancy, or death
• ITT protocol
• Kaplan-Meier curves
• One-sided stratified
log-rank test,
P=0.025
• Stratified Cox-
Proportional HRs
Secondary Overall survival (OS)
MRD negativity and transplant
rates
23. Background Brown et al. Locatelli et al. Conclusion
Outcomes-Safety
BioAgilytix. https://www.bioagilytix.com/2020/12/02/the-importance-of-cytokine-detection-and-
analysis/. Accessed March 16, 2022.
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
• Adverse events (AEs) graded
• Severe AEs= Grade 3 or higher
• Blinatumomab-related AE monitoring
• Cytokine-release syndrome
• Neurotoxicity
23
• Descriptive statistics
24. Background Brown et al. Locatelli et al. Conclusion
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
Data and Safety Monitoring Board (DSMB)
Enrollment
start
Interim Analysis
#1
Termination
24
Enrollment start Interim Analysis
#1
Interim Analysis
#2
Planned
Reality
Efficacy stopping rule: P < 0.004
Dec 2014 Sep 2019
25. Background Brown et al. Locatelli et al. Conclusion
Results-Baseline Characteristics
Characteristic Blinatumomab (n=105)
Chemotherapy
(n=103)
Median age (IQR) 9 (6-16) 9 (5-16)
Female (%) 48 (45.7%) 49 (47.6)
White 69 (83.1) 66 (74.2)
Black/African American 7 (8.4) 18 (20.2)
Hispanic/Latino 36 (37.1) 34 (34.7)
Relapse: Marrow 41 (39.0) 41 (39.8)
Relapse: Extramedullary 10 (9.5) 10 (9.7)
High-risk 69 (65.7) 69 (67.0)
Intermediate-risk 36 (34.3) 34( 33.0)
25
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
26. Background Brown et al. Locatelli et al. Conclusion
Results-Primary Outcome
Endpoint Blinatumomab (%)
(n=105)
Chemo (%)
(n=103)
HR (95% CI)
DFS rate (2-yr) 54.4 39.0 0.70 (0.47-
1.03); P=0.03
Disease Free Survival
Disease
Free
Survival
Rate
Years after randomization
• Median follow-up: 2.9 years
• 2-year disease-free survival
not statistically significant
26
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
Blinatumomab
Chemo
DFS
27. Background Brown et al. Locatelli et al. Conclusion
Results-Secondary Outcomes
Endpoint Blinatumomab (%)
(n=105)
Chemo (%)
(n=103)
HR (95% CI)
OS (2-yr) 71.3 58.4 0.62 (0.39-
0.98); P=0.02
Years after randomization
Overall
Survival
Rate
Overall Survival
• 2-year overall survival rates
statistically significant
• NNT~8
OS
Exploratory/Post-hoc
• Blinatumomab: Higher
transplant rates
27
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
Chemo
Blinatumomab
29. Background Brown et al. Locatelli et al. Conclusion
Results-Blinatumomab AEs
Cytokine-release
syndrome
22 (22%) 1 (1%) N/A N/A
Encephalopathy 15 (15%) 4 (4%) N/A N/A
Seizure 5 (5%) 1 (1%) N/A N/A
No. of patients (%)
Blinatumomab (n=102) Chemotherapy (n=97)
Any grade Grade ≥ 3 Any grade Grade ≥ 3
29
• All fully
reversible,
with no AE-
related deaths
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
30. Background Brown et al. Locatelli et al. Conclusion
Strengths and Weaknesses
• Unknown whether
DSMB was blinded
• Application limitations
• Small n
• Intermediate and high
risk only
• Majority of
participants: 9-16 y/o
• Randomization
with stratification
• Clinically
meaningful
endpoints
• Good
representation of
AEs
30
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
31. Background Brown et al. Locatelli et al. Conclusion
Conclusions
31
Brown PA, et al. JAMA. 2021;325(9):833. doi:10.1001/jama.2021.0669
Blinatumomab >
Chemotherapy
Survival
Safety DFS
Researchers
• Consolidation blinatumomab did
not result in significantly higher
DFS compared to chemotherapy.
• Study underpowered
Presenter
• Efficacy and safety of
blinatumomab in this population
is encouraging
• Larger, longer-term studies
needed
32. Background Brown et al. Locatelli et al. Conclusion
Literature Review
Effect of Blinatumomab vs Chemotherapy on
Event-Free Survival Among
Children With High-risk First-Relapse B-Cell
Acute Lymphoblastic Leukemia
A Randomized Clinical Trial
Franco Locatelli, MD, PhD; Gerhard Zugmaier,
MD; Carmelo Rizzari, MD, et al. (2021)
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987 32
33. Background Brown et al. Locatelli et al. Conclusion
•Analyze effect of blinatumomab when substituted for the
third phase of consolidation treatment on event-free survival
in patients proceeding to transplant
•Funding: Authors received personal fees, grants, or
employment from Amgen and other companies.
Objective
• Multi-center, double-blind, randomized, phase III trial
Design
• Four-week blinatumomab infusion, 15 mcg/m2/day
Intervention
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987 33
34. Background Brown et al. Locatelli et al. Conclusion
•28 days to < 18 years old
•High-risk, First-relapse B-ALL
•M1 Marrow (<5% blasts) or M2 Marrow (5-<25% blasts)
Inclusion Criteria
•Abnormal renal or hepatic function
•Ph+ ALL
•Nervous system disorders
Exclusion Criteria
34
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
35. Background Brown et al. Locatelli et al. Conclusion
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
Randomization
Randomization: Third cycle consolidation
Blinatumomab Chemotherapy
Two cycles chemotherapy consolidation
Everyone
Re-induction chemotherapy
Everyone
35
36. Background Brown et al. Locatelli et al. Conclusion
Randomization with stratification
Randomization
1-9 y/o
Chemo
Blinatumomab
<1 and > 9 y/o
Chemo
Blinatumomab
36
1:1
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
37. Background Brown et al. Locatelli et al. Conclusion
Outcomes-Efficacy
Control
EFS rate 7
months
202 total
patients+
94 events
84% power+
alpha 0.05
HR 0.63
Outcome Description Statistical Test
Primary Event-free survival (EFS):
Time from randomization to
relapse, secondary
malignancy, death, or
failure to achieve CR
• ITT protocol
• Kaplan-Meier curves with
two-sided stratified log-rank
test
• Stratified Cox-Proportional
HRs
Secondary Overall survival (OS)
Cumulative relapse
incidence, MRD status
37
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
38. Background Brown et al. Locatelli et al. Conclusion
Outcomes-Safety
• Adverse events (AEs) graded
• Blinatumomab-related AE monitoring
• Cytokine-release syndrome
• Neurotoxicity
38
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
BioAgilytix. https://www.bioagilytix.com/2020/12/02/the-importance-of-cytokine-detection-and-
analysis/. Accessed March 16, 2022.
• Descriptive statistics
39. Background Brown et al. Locatelli et al. Conclusion
Enrollment
start
Interim
Analysis #1
Termination
Enrollment
start
Interim
Analysis #1
Interim
Analysis #2
Planned
Reality
Efficacy stopping rule: P < 0.003
Nov 2015 July 2019
39
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
Data and Safety Monitoring Board (DSMB)
40. Background Brown et al. Locatelli et al. Conclusion
Results-Baseline Characteristics
Characteristic Blinatumomab (n=54)
Chemotherapy
(n=54)
Median age (range) 6 (1-17) 5 (1-17)
Boys (%) 30 (55.6) 22 (40.7)
White (%) 50 (92.6) 43 (79.6)
Asian (%) 1 (1.9) 3 (5.6)
Black or African American 0 3 (5.6)
Hispanic or Latino (%) 1 (1.9) 3 (5.6)
Favorable genetic profile 8 (14.8) 10 (18.5)
MRD > 0.1% (%) 29 (53.7) 28 (51.9%)
Mean months from first dx 21.9 (8.0) 22.8 (12.3)
40
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
41. Background Brown et al. Locatelli et al. Conclusion
Results-Primary Outcome
Endpoint Blinatumomab (%)
(n=54)
Chemo (%)
(n=54)
HR (95% CI)
EFS rates (2-
year)
66.2 27.1 0.33 (0.18-0.61)
• Median follow-up: 22.4 months
• Events: 17/54 (31.5%) with
blinatumomab versus 31/54
(57.4%) with chemo
• NNT~4 patients
Months after randomization
Survival
Probability
Event-free survival
Blinatumomab
Consolidation chemo
41
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
EFS
42. Background Brown et al. Locatelli et al. Conclusion
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
Results-Secondary Outcomes
Endpoint Blinatumomab (%)
(n=54)
Chemo (%)
(n=54)
HR (95% CI)
Death 8 (14.8) 16 (29.6) 0.43 (0.18-
1.01)
Months after randomization
Survival
Probability
Overall Survival
Blinatumomab
Consolidation chemo
• Median follow-up: 19.5
months
OS
Other
• Blinatumomab: Decreased
Cumulative incidence of relapse
42
45. Background Brown et al. Locatelli et al. Conclusion
Strengths and Weaknesses
• Small n
• “Rescue” blinatumomab
• Blinatumomab-related
AEs only in supplement
• Excluded sicker patients
(> 25% blasts)
• Application limitations
• Primarily white
• > 2/3 patients 1-9 y/o
• High-risk only
• Randomization with
stratification
• Multi-center in multiple
countries
45
46. Background Brown et al. Locatelli et al. Conclusion
Conclusions
46
Locatelli F, et al. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
Blinatumomab >
Chemotherapy
Safety
Relapse
EFS
Researchers
• Third cycle blinatumomab
consolidation treatment before
HSCT led to improved EFS,
decreased recurrence and less
toxicities
• More efficacious before HSCT
Presenter
• Blinatumomab was more effective
than chemo as the third block
• More studies needed to
understand safety and target
patients
47. Here we go again-Patient case
Today, another biopsy is obtained to evaluate LP’s status after 4 weeks
of re-induction treatment. LP’s oncologist recommends a bone marrow
transplant.
Bone Marrow
Biopsy (@ 0701)
03.16.2022 04.14.2022 Future?
• Flow
cytometry: (+)
CD19
• MRD > 0.1%
Lumbar
Puncture
• Negative for
CNS disease
Patient
Classification
• Isolated bone
marrow (BM)
B-ALL
• Early relapse
• High-risk
Is LP a candidate for Blinatumomab?
47
48. Here we go again-Patient case
B-ALL
•Age 9
•First relapse
Classification
•High risk (MRD > 0.1%)
•Early relapse
Recommend
03.16.2022 04.14.2022 Future?
48
• 15 mcg/m^2 28-day
• Hospitalize first 3 days
• Monitor: BBW events
49. 49
Background Brown et al. Locatelli et al. Conclusion
Conclusion: Just one piece of the puzzle
Efficacious and
Less Toxic
High and
intermediate-risk
relapse B-ALL
Building new
bridges to HSCT
Pechlivanoglou et al. Blood. 2021;138(Supplement 1):565-565. doi:10.1182/blood-2021-154193
50. 50
References
1. Belson M, Kingsley B, Holmes A. Risk Factors for Acute Leukemia in Children: A Review.
Environ Health Perspect. 2007;115(1):138-145. doi:10.1289/ehp.9023
2. Chang JH, Poppe MM, Hua C, Marcus KJ, Esiashvili N. Acute lymphoblastic leukemia. Pediatr
Blood Cancer. 2021;68(S2). doi:10.1002/pbc.28371
3. Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute
lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia. 2008;22(12):2142-2150.
doi:10.1038/leu.2008.251
4. Blackburn LM, Bender S, Brown S. Acute Leukemia: Diagnosis and Treatment. Semin Oncol
Nurs. 2019;35(6):150950. doi:10.1016/j.soncn.2019.150950
5. González Llano O. The complete blood count in the early diagnosis of acute leukemia in children.
Med Univ. 2016;18(73):216-218. doi:10.1016/j.rmu.2016.07.006
6. Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic
leukemia? Hematol Am Soc Hematol Educ Program. 2012;2012:129-136. doi:10.1182/asheducation-
2012.1.129
7. Hunger SP, Raetz EA. How I treat relapsed acute lymphoblastic leukemia in the pediatric
population. Blood. 2020;136(16):1803-1812. doi:10.1182/blood.2019004043
8. Pulsipher MA, Carlson C, Langholz B, et al. IgH-V(D)J NGS-MRD measurement pre- and early
post-allotransplant defines very low- and very high-risk ALL patients. Blood. 2015;125(22):3501-
3508. doi:10.1182/blood-2014-12-615757
51. 51
References
9. BLINCYTO® (blinatumomab) for injection, for intravenous use full prescribing information. Published
online February 2022. Accessed March 12, 2022.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125557s013lbl.pdf
10. Stein A, Franklin JL, Chia VM, et al. Benefit–Risk Assessment of Blinatumomab in the Treatment of
Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Drug Saf. 2019;42(5):587-601.
doi:10.1007/s40264-018-0760-1
11. Queudeville M, Ebinger M. Blinatumomab in Pediatric Acute Lymphoblastic Leukemia—From Salvage
to First Line Therapy (A Systematic Review). J Clin Med. 2021;10(12):2544. doi:10.3390/jcm10122544
12. Brown PA, Ji L, Xu X, et al. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs
Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of
B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021;325(9):833.
doi:10.1001/jama.2021.0669
13. Oskarsson T, Söderhäll S, Arvidson J, et al. Treatment-related mortality in relapsed childhood acute
lymphoblastic leukemia. Pediatr Blood Cancer. 2018;65(4):e26909. doi:10.1002/pbc.26909
14. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of Blinatumomab vs Chemotherapy on Event-Free
Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A
Randomized Clinical Trial. JAMA. 2021;325(9):843. doi:10.1001/jama.2021.0987
15. Pechlivanoglou P, Luu L, Li Q, et al. Blinatumomab Is Cost-Effective Compared to Standard Chemotherapy for
Children with High Risk Relapses of Acute Lymphoblastic Leukemia: A Cost-Effectiveness Analysis Using Population-
Based Healthcare Data. Blood. 2021;138(Supplement 1):565-565. doi:10.1182/blood-2021-154193
52. Background Brown et al. Locatelli et al. Conclusion
Thank you for your
time!
Kindpng. https://www.kindpng.com/imgv/bmJwxb_question-mark-clip-art-free-clipart-images-
image/. Accessed March 18, 2022.
52
53. Blinatumomab as Bridge Therapy to
Transplant in Pediatric Patients with
First-Relapse B-Cell Acute
Lymphoblastic Leukemia
Anna Sandler, PharmD Candidate, 2023
Pharmacy Skills IX
April 14th, 2022
53
Editor's Notes
Mercaptopurine 80 mg PO daily
Methotrexate 20 mg PO weekly
Vincristine 1.6 mg IV monthly pulses
(previous: 33 kg)
BSA= 1.095 m^2)
*Mercaptopurine, Methotrexate, Vincristine and dexamethasone
Dx: Diagnosed
2020 HF cases ~ 6 million
Estimated new cases of cancer in 2021: ~1.9 million
2021 AML: ~20K
2021 CLL: ~21 K
~4800 new ALL cases in 2021
M1: < 5%
M2: 5-25%
M3: > 25%
Although there is no consensus regarding a minimal proportion of lymphoblasts in bone marrow, the diagnosis of B-ALL/LBL should be avoided when there are <20 percent lymphoblasts
2011-2017
Re-induction: 4 weeks
IT MTX is also given to prevent or treat CNS disease
Another indication: CD19-positive B-ALL in first or second remission with MRD > 0.1%
Advise patients to refrain from driving and engaging in hazardous occupations or activities such as operating heavy machinery while Blincyto is being administered
Change to another format
US, canda, Australia, new zealnd
Early tx failure offered blinatumomab salvage therapt
Low risk results not reported
*Vincristine, dexamethasone, pegaspargase, mitoxantrone
**Dexamethasone, vincristine, cytarabine,pegaspargase/asparaginase, methotrexate, leucovorin, etoposide, risk-based IT therapy
Early tx failure: >/= 25% blasts or failure to clear CNS leukemia
High risk relapse: isolated BM or combined with extramed. < 36 months after dx or isolated extramed. < 18 months after dx
Intermediate risk: BM relapse >/= 36 mo after dx or isolated extramed. Relapse >/= 18 months after dx + MRD >/= 0.1%
Low risk: BM relapse >/= 36 months after dx or isolated extramed. Relapse >/= 18 months after dx + MRD < 0.1%
Additional strata:
Time for dx to relapse
Site of relapse
Post re-induction MRD
Date cut off: June 30, 2019
* 18-36 months after dx
* 18-36 months after dx
18-36 months after dx
Most deaths occurred within 2 years
18-36 months after dx
Most deaths occurred within 2 years
All fully reversible
All fully reversible
Change to another format
43 centers, 13 countries
Belgium, Czech repub, Denmark, France, Germany, Israel, Italy, Netheralnds, Poland, Portugal, Spain, UK,
High relapse risk: Either very early < 18 months+ isolated Extramed or very early + combined, or very early + isolated or early (18-< 6 months of completeion of primary therapy) + isolated bone marrow relapse
Components during different blocks: Dexamethasone, vincristine, ARA-C, methotrexate, cyclophosphamide, PEG-asparaginase, etoposide, daunorubicin, ifosfamide, prednisolone
Additional strata: M1 with MRD >/= 10^-3
M1 with MRD < 10^-3
And M2
Additional strata: M1 with MRD >/= 10^-3
M1 with MRD < 10^-3
And M2
4.1 month improvement in median event-free survival=clinically meaningful
Blinatumomab ADRs occurring in at least 5% of patients presented only in the supplement
What statistics did they use?
Can we calculate an NNT?
Same as stating: anywhere between 50-78% of patients will survive 2 years after re-induction therapy because recall the count from randomization to event happened AFTER re-induction treatment
Blinatumomab: 66.2 (95% CI 50.1-78.2)
Chemo: (95% CI 13.2-43.0)
Cumulative incidence of relapse;
HR= 0.24
(95% CI 0.13-0.46)
Blinatumomab ADRs occurring in at least 5% of patients presented only in the supplement
Grade 3 ADRs present in >/=3% of patients in either group
Blinatumomab ADRs occurring in at least 5% of patients presented only in the supplement
Cytokine-release syndrome: very last page of supplement
Small n difficult to know whether truly no grade 3 or 4 cytokine release events can occur with such a small number
All fully reversible
Shared clinical decision->complete substitution versus substitute for once cycle only
BSA= 1.036
24 hr infusion 1.4 mL
48 hour infusion2.8 mL
Shared clinical decision->complete substitution versus substitute for once cycle only