This document summarizes treatment strategies and quality of life considerations for elderly patients with acute myeloid leukemia (AML). It finds that while intensive chemotherapy can achieve complete remissions and improve quality of life, outcomes are poorer with age. Options for older patients include low-dose chemotherapy, hypomethylating agents like azacitidine and decitabine, and allogeneic stem cell transplant with reduced-intensity conditioning. Ongoing clinical trials are exploring post-remission azacitidine to maintain remission and quality of life achieved with initial intensive chemotherapy. Preliminary results show improved leukemia-free survival with azacitidine compared to best supportive care alone.
This document discusses challenges in treating elderly AML patients and recent advances. It notes that survival has improved over time but remains poor for those over 60. New agents target specific molecular abnormalities but a multi-agent approach is still needed. Emerging targeted therapies and hypomethylating agents are promising for some subgroups. Allogeneic stem cell transplant remains the mainstay of therapy for many high-risk patients, though reduced-toxicity conditioning regimens have increased safety for older patients eligible for transplant.
This document summarizes key findings from several studies related to acute myeloid leukemia (AML) in elderly patients:
1) A phase 3 trial found that azacitidine extended overall survival compared to conventional care regimens in older patients with newly diagnosed AML, with median OS of 10.4 months for azacitidine vs 6.5 months for conventional care.
2) Subanalyses found azacitidine provided particularly long OS benefits vs conventional care for patients with poor-risk cytogenetics (median OS 6.4 vs 3.2 months) or myelodysplasia-related changes (1-year OS 55.1% vs 31.3% for LDAC preselected
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...OSUCCC - James
This randomized clinical trial compared autologous stem cell transplantation (ASCT) versus continued therapy without transplantation in newly diagnosed multiple myeloma patients. 389 patients received induction with lenalidomide-dexamethasone (Rd) or cyclophosphamide-lenalidomide-dexamethasone (CRD). Patients were then randomized to receive ASCT or continued Rd or CRD therapy. The primary endpoint was progression-free survival (PFS). Results showed ASCT improved PFS compared to continued therapy without transplantation. However, overall survival was not significantly different between the two groups, suggesting continued therapy without ASCT may be sufficient for some patients.
Ohio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDSOSUCCC - James
This document summarizes a presentation on acute leukemias and myelodysplastic syndrome. It discusses results from the RATIFY trial showing that the addition of midostaurin to standard chemotherapy and consolidation improved overall survival in younger adults with FLT3 mutated acute myeloid leukemia compared to placebo. It also discusses results from a phase 1/2 trial showing AG-221, a mutant IDH2 inhibitor, was well-tolerated and demonstrated clinical activity in patients with IDH2 mutated hematologic malignancies.
This document discusses directions and issues in the treatment of acute myeloid leukemia (AML). It addresses challenging existing treatment dogmas regarding chemotherapy drug doses and post-remission therapies. Specifically, it summarizes several studies investigating optimal dose levels of cytarabine and anthracyclines during induction and consolidation for AML. It also reviews evidence comparing the effectiveness of autologous stem cell transplantation versus chemotherapy alone as post-remission consolidation approaches. The document advocates moving beyond conventional chemotherapy regimens to more personalized precision medicine approaches for AML patients.
This document discusses challenges in treating elderly AML patients and recent advances. It notes that survival has improved over time but remains poor for those over 60. New agents target specific molecular abnormalities but a multi-agent approach is still needed. Emerging targeted therapies and hypomethylating agents are promising for some subgroups. Allogeneic stem cell transplant remains the mainstay of therapy for many high-risk patients, though reduced-toxicity conditioning regimens have increased safety for older patients eligible for transplant.
This document summarizes key findings from several studies related to acute myeloid leukemia (AML) in elderly patients:
1) A phase 3 trial found that azacitidine extended overall survival compared to conventional care regimens in older patients with newly diagnosed AML, with median OS of 10.4 months for azacitidine vs 6.5 months for conventional care.
2) Subanalyses found azacitidine provided particularly long OS benefits vs conventional care for patients with poor-risk cytogenetics (median OS 6.4 vs 3.2 months) or myelodysplasia-related changes (1-year OS 55.1% vs 31.3% for LDAC preselected
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...OSUCCC - James
This randomized clinical trial compared autologous stem cell transplantation (ASCT) versus continued therapy without transplantation in newly diagnosed multiple myeloma patients. 389 patients received induction with lenalidomide-dexamethasone (Rd) or cyclophosphamide-lenalidomide-dexamethasone (CRD). Patients were then randomized to receive ASCT or continued Rd or CRD therapy. The primary endpoint was progression-free survival (PFS). Results showed ASCT improved PFS compared to continued therapy without transplantation. However, overall survival was not significantly different between the two groups, suggesting continued therapy without ASCT may be sufficient for some patients.
Ohio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDSOSUCCC - James
This document summarizes a presentation on acute leukemias and myelodysplastic syndrome. It discusses results from the RATIFY trial showing that the addition of midostaurin to standard chemotherapy and consolidation improved overall survival in younger adults with FLT3 mutated acute myeloid leukemia compared to placebo. It also discusses results from a phase 1/2 trial showing AG-221, a mutant IDH2 inhibitor, was well-tolerated and demonstrated clinical activity in patients with IDH2 mutated hematologic malignancies.
This document discusses directions and issues in the treatment of acute myeloid leukemia (AML). It addresses challenging existing treatment dogmas regarding chemotherapy drug doses and post-remission therapies. Specifically, it summarizes several studies investigating optimal dose levels of cytarabine and anthracyclines during induction and consolidation for AML. It also reviews evidence comparing the effectiveness of autologous stem cell transplantation versus chemotherapy alone as post-remission consolidation approaches. The document advocates moving beyond conventional chemotherapy regimens to more personalized precision medicine approaches for AML patients.
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
This document summarizes molecular genetics guiding treatment of acute myeloid leukemia (AML). Over 100 genetic lesions have been identified in AML. New molecular markers do not currently impact clinical practice due to heterogeneity, study design limitations, and lack of predictive value. Genomic profiling of over 1,500 AML patients identified 11 non-overlapping molecular classes and over 5,000 driver mutations involving 77 loci. Certain mutations like FLT3, KIT, IDH1/2 inform targeted therapy approaches in clinical trials. Phase III trials are investigating chemotherapy with or without targeted agents like midostaurin, dasatinib and quizartinib in genetically defined AML patient subgroups.
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTSOSUCCC - James
This document summarizes key abstracts presented at the American Society of Hematology (ASH) 2015 conference related to lymphoma subtypes including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin's lymphoma (HL). For MCL, abstracts showed that bortezomib maintenance after immunochemotherapy and stem cell transplant improved progression-free survival compared to consolidation or historical controls. Pre-transplant treatment with R-bendamustine induced high rates of minimal residual disease negativity associated with improved outcomes. For DLBCL, adding bortezomib to R-CHOP in non-germinal center subtype showed improved response rates
Update on Systemic Therapy for Metastatic Pancreas AdenocarcinomaOSUCCC - James
The document discusses treatment options for metastatic pancreatic cancer. For first-line therapy, FOLFIRINOX is an option but is reserved for younger, healthier patients due to toxicity. Gemcitabine plus nab-paclitaxel is a preferred first-line option. For second-line therapy after progression on gemcitabine, nanoliposomal irinotecan plus 5-FU/LV has shown a survival benefit compared to 5-FU/LV alone. Molecular profiling of pancreatic tumors has identified subtypes that could help guide targeted therapies, and immune-based approaches also offer promise. The James Cancer Hospital is conducting clinical trials evaluating novel combinations for both first-line and second-line metastatic pancreatic cancer
Here are a few key points regarding carfilzomib-associated cardiac adverse events based on clinical trial data:
- CHF and hypertension are the most common cardiac AEs seen with carfilzomib. Rates are generally higher than with bortezomib or lenalidomide doublets.
- Hypertension can usually be managed medically with antihypertensives like ACE inhibitors. Close monitoring of BP is important.
- Risk factors for cardiac AEs include older age, prior cardiac history, diabetes, renal dysfunction. However, events can still occur in lower risk patients.
- No definitive biomarkers yet to reliably predict risk. Troponin elevation during treatment may indicate higher risk but
1) Hematopoietic stem cell transplantation (HSCT) can cure thalassemia patients by replacing defective bone marrow with healthy donor marrow.
2) A study of 98 thalassemia patients who received HSCT found that 94% survived with a novel reduced toxicity conditioning regimen having similar outcomes as standard regimens.
3) HSCT can cure thalassemia patients of all ages, including those over 10 years old, with survival rates over 90% found in the study. Gene therapy may also provide a cure in the future without requiring donors.
1) The document summarizes research on donor selection for haploidentical hematopoietic stem cell transplantation (HSCT). It finds that donor-specific anti-HLA antibodies were associated with primary graft failure after unmanipulated haploidentical HSCT.
2) Specifically, the research studied 345 HSCT recipients and found that 25.2% had donor-specific anti-HLA antibodies, and those with higher antibody levels had higher rates of graft rejection and poor graft function.
3) Patients who experienced primary graft failure due to these antibodies had inferior survival outcomes compared to those without graft failure. The results suggest donor-specific antibodies should be considered when selecting a haploidentical donor.
Ideal induction regimen for AML in adolescents and young adults spa718
This document discusses considerations for treatment of acute myeloid leukemia (AML) in adolescent and young adult (AYA) patients between ages 15-29. It covers several key points:
1) Overcoming the kinetics of AML through dose-escalated chemotherapy and addition of a third agent.
2) Understanding the disease biology through studies like TCGA and determining the right targeted partners.
3) Whether all younger age groups require the same treatment approach given differences in biology and outcomes between teenagers, 20s, etc.
4) The role of consolidation and bone marrow transplantation.
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINI...Alok Gupta
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINICAL OUTCOME INACUTE LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
Updates On Upper Gastrointestinal Malignancies 2015OSUCCC - James
Updates On Upper Gastrointestinal Malignancies 2015
Tanios Bekaii-Saab, MD
Chief , Section of Gastrointestinal Cancers
Disease Specific Research Group Leader
Professor of Medicine and Pharmacy
OSUCCC- Arthur James Cancer Hospital
TREATMENT OF NON-HIDGKIN'S LYMPHOMA IN ELDERLY PATIENTSspa718
This document summarizes treatment approaches for non-Hodgkin's lymphoma in elderly patients. It discusses palliative options for refractory/relapsed diffuse large B-cell lymphoma such as gemcitabine-based chemotherapy, low-dose oral chemotherapy, and hyperfractionated cyclophosphamide. It also reviews novel anti-CD20 monoclonal antibodies showing efficacy against relapsed/refractory indolent lymphoma, and brentuximab vedotin's mechanism of action and responses seen in relapsed/refractory systemic anaplastic large cell lymphoma. Finally, it provides a high-level overview of the MD Anderson Cancer Center's Department of Lymphoma/Myeloma and its disease-specific
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoMauricio Lema
Ponencia en el VII Congreso internacional de coloproctología, Bogotá, 18.08.2016. Con énfasis en los estudios recientes en terapia antiangiogénica, y el impacto del lado del primario en el pronóstico (y aspectos predictivos) de la enfermedad metastásica.
1) The document discusses response rates and outcomes for patients with chronic myeloid leukemia (CML) treated with various tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, nilotinib, and bosutinib.
2) It reports that achieving a major cytogenetic response or deeper molecular response (e.g. MMR) at certain timepoints (e.g. 12 months) on imatinib is associated with improved progression-free and overall survival.
3) For patients who become resistant or intolerant to imatinib, the second-generation TKIs dasatinib, nilotinib and bosutinib have response rates ranging from
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
Imatinib vs. 2nd gen TKI in newly diagnosed Chronic Myelogenous Leukemia spa718
This document summarizes results from the ENESTnd clinical trial comparing imatinib to nilotinib in the treatment of chronic myeloid leukemia. The key findings from the 5-year update are:
- Nilotinib resulted in significantly higher rates of major molecular response and molecular response 4.5 or greater compared to imatinib. Over half of nilotinib-treated patients achieved MR4.5 by 5 years.
- Progression to accelerated or blast crisis phase was lower in both nilotinib arms compared to imatinib, with rates of 3.5%, 2.1%, and 7.1% respectively.
- Overall survival and progression-free survival did not
This document reviews treatments for neuroendocrine tumors (NETs), including peptide receptor radionuclide therapy (PRRT). It summarizes the evidence for various NET treatment options such as surgery, somatostatin analogs, PRRT, chemotherapy, and targeted therapies. It also provides an overview of a PRRT treatment day and integrates PRRT with other NET therapies. Clinical trial data is presented demonstrating the efficacy of PRRT and targeted therapies such as everolimus and sunitinib in extending progression-free survival for NETs. The conclusion emphasizes treating NETs only when necessary and considering surgery first followed by somatostatin analogs, PRRT, intra-arterial therapies,
This document provides an overview of cholangiocarcinoma, a rare and deadly form of cancer. It discusses risk factors and increasing incidence rates. For localized disease, surgical resection is standard but outcomes remain poor. For advanced disease, gemcitabine-based chemotherapy is the standard first-line treatment based on results from the ABC-02 trial showing improved survival with gemcitabine and cisplatin. Retrospective data on second-line therapies and combination of pazopanib and trametinib show some benefit. Adding radiation therapy may also improve outcomes based on another retrospective review. Next generation sequencing is helping identify molecular alterations to guide targeted therapy trials. Ongoing clinical trials at MD Anderson include testing new
4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ ΡΟΔΟΥ: Εξελίξεις στη θεραπεία του πλακώδους κα...isrodoy isr
The document discusses recent developments in the treatment of non-small cell lung cancer (NSCLC). It summarizes several key studies that have established new standards of care and treatment options for NSCLC. These include the use of pemetrexed or albumin-bound paclitaxel in combination with platinum chemotherapy as first-line options. Targeted therapies such as necitumumab for squamous cell NSCLC and the addition of bevacizumab or cetuximab to chemotherapy based on tumor biomarkers are also discussed. Studies establishing the role of the anti-VEGF antibody ramucirumab in combination with docetaxel in the second-line setting are summarized.
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
This document summarizes molecular genetics guiding treatment of acute myeloid leukemia (AML). Over 100 genetic lesions have been identified in AML. New molecular markers do not currently impact clinical practice due to heterogeneity, study design limitations, and lack of predictive value. Genomic profiling of over 1,500 AML patients identified 11 non-overlapping molecular classes and over 5,000 driver mutations involving 77 loci. Certain mutations like FLT3, KIT, IDH1/2 inform targeted therapy approaches in clinical trials. Phase III trials are investigating chemotherapy with or without targeted agents like midostaurin, dasatinib and quizartinib in genetically defined AML patient subgroups.
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTSOSUCCC - James
This document summarizes key abstracts presented at the American Society of Hematology (ASH) 2015 conference related to lymphoma subtypes including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin's lymphoma (HL). For MCL, abstracts showed that bortezomib maintenance after immunochemotherapy and stem cell transplant improved progression-free survival compared to consolidation or historical controls. Pre-transplant treatment with R-bendamustine induced high rates of minimal residual disease negativity associated with improved outcomes. For DLBCL, adding bortezomib to R-CHOP in non-germinal center subtype showed improved response rates
Update on Systemic Therapy for Metastatic Pancreas AdenocarcinomaOSUCCC - James
The document discusses treatment options for metastatic pancreatic cancer. For first-line therapy, FOLFIRINOX is an option but is reserved for younger, healthier patients due to toxicity. Gemcitabine plus nab-paclitaxel is a preferred first-line option. For second-line therapy after progression on gemcitabine, nanoliposomal irinotecan plus 5-FU/LV has shown a survival benefit compared to 5-FU/LV alone. Molecular profiling of pancreatic tumors has identified subtypes that could help guide targeted therapies, and immune-based approaches also offer promise. The James Cancer Hospital is conducting clinical trials evaluating novel combinations for both first-line and second-line metastatic pancreatic cancer
Here are a few key points regarding carfilzomib-associated cardiac adverse events based on clinical trial data:
- CHF and hypertension are the most common cardiac AEs seen with carfilzomib. Rates are generally higher than with bortezomib or lenalidomide doublets.
- Hypertension can usually be managed medically with antihypertensives like ACE inhibitors. Close monitoring of BP is important.
- Risk factors for cardiac AEs include older age, prior cardiac history, diabetes, renal dysfunction. However, events can still occur in lower risk patients.
- No definitive biomarkers yet to reliably predict risk. Troponin elevation during treatment may indicate higher risk but
1) Hematopoietic stem cell transplantation (HSCT) can cure thalassemia patients by replacing defective bone marrow with healthy donor marrow.
2) A study of 98 thalassemia patients who received HSCT found that 94% survived with a novel reduced toxicity conditioning regimen having similar outcomes as standard regimens.
3) HSCT can cure thalassemia patients of all ages, including those over 10 years old, with survival rates over 90% found in the study. Gene therapy may also provide a cure in the future without requiring donors.
1) The document summarizes research on donor selection for haploidentical hematopoietic stem cell transplantation (HSCT). It finds that donor-specific anti-HLA antibodies were associated with primary graft failure after unmanipulated haploidentical HSCT.
2) Specifically, the research studied 345 HSCT recipients and found that 25.2% had donor-specific anti-HLA antibodies, and those with higher antibody levels had higher rates of graft rejection and poor graft function.
3) Patients who experienced primary graft failure due to these antibodies had inferior survival outcomes compared to those without graft failure. The results suggest donor-specific antibodies should be considered when selecting a haploidentical donor.
Ideal induction regimen for AML in adolescents and young adults spa718
This document discusses considerations for treatment of acute myeloid leukemia (AML) in adolescent and young adult (AYA) patients between ages 15-29. It covers several key points:
1) Overcoming the kinetics of AML through dose-escalated chemotherapy and addition of a third agent.
2) Understanding the disease biology through studies like TCGA and determining the right targeted partners.
3) Whether all younger age groups require the same treatment approach given differences in biology and outcomes between teenagers, 20s, etc.
4) The role of consolidation and bone marrow transplantation.
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINI...Alok Gupta
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINICAL OUTCOME INACUTE LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
Updates On Upper Gastrointestinal Malignancies 2015OSUCCC - James
Updates On Upper Gastrointestinal Malignancies 2015
Tanios Bekaii-Saab, MD
Chief , Section of Gastrointestinal Cancers
Disease Specific Research Group Leader
Professor of Medicine and Pharmacy
OSUCCC- Arthur James Cancer Hospital
TREATMENT OF NON-HIDGKIN'S LYMPHOMA IN ELDERLY PATIENTSspa718
This document summarizes treatment approaches for non-Hodgkin's lymphoma in elderly patients. It discusses palliative options for refractory/relapsed diffuse large B-cell lymphoma such as gemcitabine-based chemotherapy, low-dose oral chemotherapy, and hyperfractionated cyclophosphamide. It also reviews novel anti-CD20 monoclonal antibodies showing efficacy against relapsed/refractory indolent lymphoma, and brentuximab vedotin's mechanism of action and responses seen in relapsed/refractory systemic anaplastic large cell lymphoma. Finally, it provides a high-level overview of the MD Anderson Cancer Center's Department of Lymphoma/Myeloma and its disease-specific
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoMauricio Lema
Ponencia en el VII Congreso internacional de coloproctología, Bogotá, 18.08.2016. Con énfasis en los estudios recientes en terapia antiangiogénica, y el impacto del lado del primario en el pronóstico (y aspectos predictivos) de la enfermedad metastásica.
1) The document discusses response rates and outcomes for patients with chronic myeloid leukemia (CML) treated with various tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, nilotinib, and bosutinib.
2) It reports that achieving a major cytogenetic response or deeper molecular response (e.g. MMR) at certain timepoints (e.g. 12 months) on imatinib is associated with improved progression-free and overall survival.
3) For patients who become resistant or intolerant to imatinib, the second-generation TKIs dasatinib, nilotinib and bosutinib have response rates ranging from
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
Imatinib vs. 2nd gen TKI in newly diagnosed Chronic Myelogenous Leukemia spa718
This document summarizes results from the ENESTnd clinical trial comparing imatinib to nilotinib in the treatment of chronic myeloid leukemia. The key findings from the 5-year update are:
- Nilotinib resulted in significantly higher rates of major molecular response and molecular response 4.5 or greater compared to imatinib. Over half of nilotinib-treated patients achieved MR4.5 by 5 years.
- Progression to accelerated or blast crisis phase was lower in both nilotinib arms compared to imatinib, with rates of 3.5%, 2.1%, and 7.1% respectively.
- Overall survival and progression-free survival did not
This document reviews treatments for neuroendocrine tumors (NETs), including peptide receptor radionuclide therapy (PRRT). It summarizes the evidence for various NET treatment options such as surgery, somatostatin analogs, PRRT, chemotherapy, and targeted therapies. It also provides an overview of a PRRT treatment day and integrates PRRT with other NET therapies. Clinical trial data is presented demonstrating the efficacy of PRRT and targeted therapies such as everolimus and sunitinib in extending progression-free survival for NETs. The conclusion emphasizes treating NETs only when necessary and considering surgery first followed by somatostatin analogs, PRRT, intra-arterial therapies,
This document provides an overview of cholangiocarcinoma, a rare and deadly form of cancer. It discusses risk factors and increasing incidence rates. For localized disease, surgical resection is standard but outcomes remain poor. For advanced disease, gemcitabine-based chemotherapy is the standard first-line treatment based on results from the ABC-02 trial showing improved survival with gemcitabine and cisplatin. Retrospective data on second-line therapies and combination of pazopanib and trametinib show some benefit. Adding radiation therapy may also improve outcomes based on another retrospective review. Next generation sequencing is helping identify molecular alterations to guide targeted therapy trials. Ongoing clinical trials at MD Anderson include testing new
4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ ΡΟΔΟΥ: Εξελίξεις στη θεραπεία του πλακώδους κα...isrodoy isr
The document discusses recent developments in the treatment of non-small cell lung cancer (NSCLC). It summarizes several key studies that have established new standards of care and treatment options for NSCLC. These include the use of pemetrexed or albumin-bound paclitaxel in combination with platinum chemotherapy as first-line options. Targeted therapies such as necitumumab for squamous cell NSCLC and the addition of bevacizumab or cetuximab to chemotherapy based on tumor biomarkers are also discussed. Studies establishing the role of the anti-VEGF antibody ramucirumab in combination with docetaxel in the second-line setting are summarized.
1) Early molecular response at 3 months is an important predictor of long-term outcomes for CML patients on TKI therapy. Failure to achieve BCR-ABL ≤10% at 3 months is associated with higher risk of disease progression or death.
2) Achieving deeper levels of response such as MMR and MR4.5 is associated with improved progression-free and overall survival compared to lesser responses. TKIs like nilotinib and dasatinib have shown higher rates of deep molecular response compared to imatinib.
3) Avoiding progression to advanced phases such as accelerated or blast crisis is critical for long-term survival, as outcomes are much poorer once CML progresses beyond chronic phase
Acute Lymphoblastic Leukaemia (ALL) in Childrenspa718
This document summarizes key points about acute lymphoblastic leukemia (ALL) in children, including:
1) ALL is the most common childhood cancer. Survival rates have improved from less than 10% in the 1960s to over 90% currently due to effective chemotherapy regimens developed through large clinical trials.
2) Proper use of chemotherapy through randomized clinical trials testing different drug combinations, dosages, and timings has been key to improved outcomes. Studies have also tailored treatment intensity based on patient risk factors.
3) Monitoring of minimal residual disease allows further stratification of patients into risk groups to guide therapy. New drugs like imatinib have also improved survival for rare high-risk subtypes.
Report Back from San Antonio Breast Cancer Symposium: Spotlight on MBCbkling
Dr. Virginia Kaklamani, Leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, will share her biggest takeaways from the latest research presented at the San Antonio Breast Cancer Symposium (SABCS) 2019 with a focus on metastatic breast cancer.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
This document summarizes the current state of targeted therapies for metastatic renal cell cancer. It discusses several front-line standard of care options including sunitinib, pazopanib, and bevacizumab with interferon. Ongoing areas of investigation mentioned include more potent VEGF inhibitors, biomarkers of response and resistance, alternative dosing schedules, and immunotherapy combinations with targeted agents.
Sequencing therapy for crcp a practical approachMohamed Abdulla
This document discusses sequencing therapy for castration-resistant prostate cancer (CRPC). It provides an overview of prostate cancer as an androgenic disease and summarizes several key clinical trials investigating the efficacy of abiraterone and enzalutamide in both pre-docetaxel and post-docetaxel CRPC patients. It concludes by presenting NCCN guidelines for sequencing CRPC therapies based on disease stage and symptoms.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
Approach to Ovarian Cancer Class 0703.pptxRupesh Singh
This document provides data on cancer incidence rates from various sites in rural and urban South and West India. It shows that cervix, breast and ovarian cancer rates were highest in urban areas of Chennai and Mumbai compared to rural areas of Dindugul and Barshi for the time periods of 2003-2006 and 2004-2005. The total cancer rates per 100,000 people were also higher in the urban versus rural locations. For example, the total cancer rate in Chennai was 118 per 100,000 versus 62.6 per 100,000 in Dindugul. This suggests that cancer incidence rates are higher in urban versus rural parts of India.
Similar to Oliva esther aml eurasian st. petersburg 2016 (20)
This document discusses the molecular genetics and cytogenetics of acute lymphoblastic leukemia (ALL) and how characterization has improved over time. Key points include:
- Identification of genetic subgroups like Ph+ ALL has allowed for biologically-based prognostic stratification and targeted therapies.
- The GIMEMA network in Italy has characterized over 5,000 ALL cases since the 1980s using techniques like cytogenetics, FISH, and molecular genetics to define subgroups.
- Specific mutations like BCR-ABL, IKZF1 deletions, and CRLF2 deregulation are associated with poorer outcomes in certain ALL subgroups.
Oliva esther qol symposium eurasian st. petersburg 2016EAFO2014
Patients with hematological malignancies experience quality of life issues related to their disease and treatment. Common problems include fatigue, pain, and disruptions to daily activities and social relationships. Conditions like multiple myeloma, myelodysplastic syndromes, and chronic myeloid leukemia are associated with fatigue, while neutropenia from treatments can cause weakness and infections. Transfusions for anemia in myelodysplastic syndromes negatively impact quality of life. Younger patients with chronic myeloid leukemia have greater impairments. Assessments of quality of life and symptoms provide important information for evaluating patients' disease status and response to treatment over time in clinical practice.
This document discusses modern treatment strategies for diffuse large B-cell lymphoma (DLBCL). It summarizes that DLBCL is molecularly distinct diseases with different biological characteristics and outcomes. Targeted therapies like ibrutinib and lenalidomide show promise for the activated B-cell (ABC) subtype of DLBCL. Monitoring circulating tumor DNA is presented as a very promising tool for early detection of treatment failure or recurrence, which can allow for pre-emptive treatment changes or early intervention.
Sam Salek eurasian conference 040316 st petersburgEAFO2014
The document discusses the importance of using patient-reported outcome information to aid treatment decision-making for patients with hematological malignancies. It summarizes discussions and meetings from the European Hematology Association's Scientific Working Group on Quality of Life and Symptoms over several years on developing guidelines and tools to measure important issues for patients, including fatigue, physical appearance changes, cognitive impacts, emotional impacts, and long-term effects. The goal is to develop a new tool that can be used at any stage of the disease to incorporate the patient perspective into treatment decisions.
Fedorenko_Denis_A.novik memorial lecture iv hematology forum_2016_st.pEAFO2014
AHSCT is a promising therapy for MS that can provide both clinical and patient-reported benefits. AHSCT using a BEAM-like conditioning regimen followed by mitoxantrone consolidation therapy resulted in 100% MRI response at 6 months, 55-68% improvement on EDSS scores, and improved quality of life outcomes based on SF-36 scores. The addition of mitoxantrone consolidation therapy after AHSCT may further improve event-free survival rates compared to AHSCT alone. Long-term follow up of patients undergoing AHSCT continues to show stabilization or improvement in neurological function for the majority of patients.
Fedorenko_Denis iv hematology forum_2016_st.pEAFO2014
This study examined quality of life (QoL) in 124 Hodgkin's lymphoma patients before autologous hematopoietic stem cell transplantation (AHSCT) and analyzed its prognostic value. QoL was assessed using the SF-36 questionnaire and compared to a control population. Patients had worse QoL than controls, especially in physical, role physical, emotional, and social functioning. While no differences in QoL were found between clinical response groups, overall survival at 19 months was lower in patients with severe/critical QoL impairment before AHSCT (66.7%) compared to those with no/mild impairment (78%). The results suggest QoL may be a prognostic factor for Hodgkin's
This document discusses bridging the gap between laboratory diagnostics and patient care. It provides several case studies where the hematologist was able to identify additional information or the correct diagnosis by reviewing blood test results in the context of the patient's clinical presentation. This allowed conditions to be correctly identified and managed, avoiding missed diagnoses. The document emphasizes the importance of bi-directional communication between laboratory specialists and clinicians to ensure test results are fully validated and applied to improve patient outcomes.
This presentation by Juraj Čorba, Chair of OECD Working Party on Artificial Intelligence Governance (AIGO), was made during the discussion “Artificial Intelligence, Data and Competition” held at the 143rd meeting of the OECD Competition Committee on 12 June 2024. More papers and presentations on the topic can be found at oe.cd/aicomp.
This presentation was uploaded with the author’s consent.
This presentation by OECD, OECD Secretariat, was made during the discussion “Competition and Regulation in Professions and Occupations” held at the 77th meeting of the OECD Working Party No. 2 on Competition and Regulation on 10 June 2024. More papers and presentations on the topic can be found at oe.cd/crps.
This presentation was uploaded with the author’s consent.
This presentation by Yong Lim, Professor of Economic Law at Seoul National University School of Law, was made during the discussion “Artificial Intelligence, Data and Competition” held at the 143rd meeting of the OECD Competition Committee on 12 June 2024. More papers and presentations on the topic can be found at oe.cd/aicomp.
This presentation was uploaded with the author’s consent.
Mastering the Concepts Tested in the Databricks Certified Data Engineer Assoc...SkillCertProExams
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This presentation by Professor Alex Robson, Deputy Chair of Australia’s Productivity Commission, was made during the discussion “Competition and Regulation in Professions and Occupations” held at the 77th meeting of the OECD Working Party No. 2 on Competition and Regulation on 10 June 2024. More papers and presentations on the topic can be found at oe.cd/crps.
This presentation was uploaded with the author’s consent.
XP 2024 presentation: A New Look to Leadershipsamililja
Presentation slides from XP2024 conference, Bolzano IT. The slides describe a new view to leadership and combines it with anthro-complexity (aka cynefin).
This presentation by OECD, OECD Secretariat, was made during the discussion “Pro-competitive Industrial Policy” held at the 143rd meeting of the OECD Competition Committee on 12 June 2024. More papers and presentations on the topic can be found at oe.cd/pcip.
This presentation was uploaded with the author’s consent.
Carrer goals.pptx and their importance in real lifeartemacademy2
Career goals serve as a roadmap for individuals, guiding them toward achieving long-term professional aspirations and personal fulfillment. Establishing clear career goals enables professionals to focus their efforts on developing specific skills, gaining relevant experience, and making strategic decisions that align with their desired career trajectory. By setting both short-term and long-term objectives, individuals can systematically track their progress, make necessary adjustments, and stay motivated. Short-term goals often include acquiring new qualifications, mastering particular competencies, or securing a specific role, while long-term goals might encompass reaching executive positions, becoming industry experts, or launching entrepreneurial ventures.
Moreover, having well-defined career goals fosters a sense of purpose and direction, enhancing job satisfaction and overall productivity. It encourages continuous learning and adaptation, as professionals remain attuned to industry trends and evolving job market demands. Career goals also facilitate better time management and resource allocation, as individuals prioritize tasks and opportunities that advance their professional growth. In addition, articulating career goals can aid in networking and mentorship, as it allows individuals to communicate their aspirations clearly to potential mentors, colleagues, and employers, thereby opening doors to valuable guidance and support. Ultimately, career goals are integral to personal and professional development, driving individuals toward sustained success and fulfillment in their chosen fields.
This presentation by Nathaniel Lane, Associate Professor in Economics at Oxford University, was made during the discussion “Pro-competitive Industrial Policy” held at the 143rd meeting of the OECD Competition Committee on 12 June 2024. More papers and presentations on the topic can be found at oe.cd/pcip.
This presentation was uploaded with the author’s consent.
Collapsing Narratives: Exploring Non-Linearity • a micro report by Rosie WellsRosie Wells
Insight: In a landscape where traditional narrative structures are giving way to fragmented and non-linear forms of storytelling, there lies immense potential for creativity and exploration.
'Collapsing Narratives: Exploring Non-Linearity' is a micro report from Rosie Wells.
Rosie Wells is an Arts & Cultural Strategist uniquely positioned at the intersection of grassroots and mainstream storytelling.
Their work is focused on developing meaningful and lasting connections that can drive social change.
Please download this presentation to enjoy the hyperlinks!
4. Whatever the age, CR is an essential prerequisite
for achieving long-term survival or cure
Ferrara et al, Clinical Geriatrics, 2000
Patients aged 75
yrs or older
5. Optimal active treatment strategies differ
depending on patient factors
Chemotherapy
Autologous HSCT
Allogeneic HSCT
Standard-dose
chemotherapy (7+3)
High-dose cytarabine
Low-dose cytarabine
Hypomethylating agents*
Clinical trial
Clinical trial
RIC HSCT
Hypomethylating agents*
Consolidation therapy
With the aim to maintain remission
Induction therapy
With the aim to eradicate the leukaemic clone
NCCN guidelines Acute Myeloid Leukaemia v2.2014
Available at NCCN.org. Accessed April 2014
*Azacitidine or decitabine
RIC = reduced intensity conditioning
7. Some older patients receive low-dose
cytarabine, but outcomes are generally poor
Survival
Prospective randomised trial to evaluate treatment outcomes with LDAC versus hydroxyurea in 202 patients
(≥60 years old: 98%) with AML (86%) or MDS (14%) ineligible for standard chemotherapy
LDAC (n=103)
HU (n=99)
Time, years
Patients,%
Burnett AK, et al. Cancer 2007;109:1114–24
LDAC = low-dose cytarabine
HU = hydroxyurea
Median OS with LDAC: ~4 months
8. 7+3 – the mainstay of IC for patients with AML1
0 3 Days of the cycle
Cytarabine
100mg/m2
Anthracycline
IDA 12mg/m2 OR
mitoxantrone 12mg/m2 OR
DNR 40–50mg/m2
7 21 28
Response assessment
day +21–282
7+3 induction chemotherapy for AML is recommended for patients who are
considered able to tolerate it
1. Roboz GJ, et al. Curr Opin Oncol 2012;24:711–9
2. Dohner H, et al. Blood 2010;115:453–74IC = Intensive Chemotherapy; DNR = daunorubicin; IDA = idarubicin
9. Survival according to age in AML patients
eligible for IC
1. Appelbaum FR, et al. Blood 2006;107:3481–5
Survival
18,8
9,0
6,9
3,5
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
20,0
SurvivalTime,months
≤56
(n=368)
56–65
(n=246)
66–75
(n=274)
Age, years
≥75
(n=80)
Retrospective analysis of treatment outcomes in 968 patients with AML1
IC = Intensive Chemotherapy
12. EBMT risk scoring can help identify patients who
may benefit from allogeneic HSCT
Investigation of the EBMT risk score* for predicting outcomes after allogeneic HSCT in a cohort of
56,505 patients with haematological disorders1
1. Gratwohl A, et al. Cancer 2009;115:1087–92
*Based on five pre-transplant factors: AGE of the patient, disease stage, time from diagnosis to
transplant, donor type, and donor-recipient sex combination.
EBMT = European Group for Blood and Marrow Transplantation
TRM = transplant-related mortality
OS
Years after transplantation
0
0.2
0.4
0.6
0.8
1.0
Probabilityofsurvival
0 1 2 3 4 5
TRM
Years after transplantation
0
0.2
0.4
0.6
0.8
1.0
ProbabilityofTRM
0 1 2 3 4 5
Score 0
Score 1
Score 2
Score 3
Score 4
Score 5
Score 6–7
13. Long-term outcome of reduced-intensity
allogeneic HSCT in AML patients in CR
Popat U, et al. BMT 2012
14. RIC HSCT may be preferred over IC for selected
patients with AML
RIC HSCT can be an option for some older AML patients or those unfit for standard transplant
Retrospective analysis of allogeneic HSCT (61% using a RIC regimen, usually including fludarabine) versus IC
990 eligible patients with AML (median age 60 [range 50–70])
Relapse
IC only (n=838)
HSCT (n=152)
p=0.001
Kurosawa S, et al. Biol Blood Marrow Transplant 2011;17:401–11IC= intensive chemotherapy; RIC = reduced intensity conditioning
Years from CR1
0
0.2
0.4
0.6
0.8
1.0
Cumulativerisk
0 1 2 3 4 5
OS
p=0.012
Years from CR1
0
0.2
0.4
0.6
0.8
1.0
Cumulativesurvival
0 1 2 3 4 5
15. Non relapse mortality is higher in patients
receiving a RIC HSCT
Kurosawa S, et al. Biol Blood Marrow Transplant 2011;17:401–11NRM = non-relapse mortality
NRM
IC alone (n=838)
HSCT (n=152)
p<0.001
Years from CR1
0
0.2
0.4
0.6
0.8
1.0
CumulativeNRM
0 1 2 3 4 5
16. Quality of Life in Elderly Patients with
Acute Myeloid Leukemia undergoing
Induction Chemotherapy
17. <60 yrs (n=142) ≥60 yrs(n=97)
QoL Domain mean (SD) mean (SD) P-value
Global Health / QOL 45.7 (26.9) 45.7 (26.5) 0.99
Physical Functioning 74.2 (25.8) 75.4 (27.9) 0.75
Role Functioning 44.9 (33.2) 48.7 (37.4) 0.41
Emotional Functioning 64.9 (25.1) 72.6 (23.8) 0.02
Cognitive Functioning 74.9 (24.7) 76.7 (24.8) 0.59
Social Functioning 42.2 (33.1) 55.2 (34.3) 0.004
FACT-F (0-52) 29.0 (12.9) 30.3 (13.9) 0.48
ESAS Global Fatigue (0-10) 5.2 (2.5) 5.2 (2.6) 0.82
Impact of age on Quality of Life (QoL) in
patients with AML
N= 239(median age 57.5 yrs)
Instruments: EORTC QLQ-C30 e FACT-F
Timilshina N et al. Annals of Oncology 2014 ; 25: 883–888
18. QoL in elderly patients with AML at diagnosis
113 cases > 60 yrs
Mean age 72 yrs (± 6)
48 (42%) IC
65 (58%) palliative care
Oliva EN et al. Haematologica 2011; 96(5): 696-702IT= IC; PT= palliative care
Items addressed by QOL-E Disease-specific:
•Dyspnea (shortness of breath)
•Dependence on hospital and staff
•Dependence on transfusions
19. 61 elderly patients with AML undergoing IC
EORTC QLQ-C30 QoL instrument
28 evaluable for QOL changes (only responders)
Improvements in QoL after induction+consolidation:
Physical Functioning (p<0.001)
Role Functioning (p=0.001)
Emotional Functioning (p< 0.001)
Social Functioning (p=0.007)
Schumacher et al. Leukemia 1998 Apr; 12(4):586-92
Improvement in QoL in elderly AML patients
in CR after IC
QoL= Quality of life
IC= intensive chemotherapy
20. Conclusions: Patient reported outcome benefits overcome
adverse events in elderly patients obtaining a CR with IC.
*Significant improvements in
Fatigue
Nausea
Vomiting
Loss of appetite
Insomnia
*p< 0.001
IC= intensive chemotherapy
Improvement of symptoms in elderly patients in
CR after IC
Schumacher et al. Leukemia 1998 Apr; 12(4):586-92
21. Primary
Difference in 2- and 5-year DFS between 5-Aza and BSC arms.
Secondary
Difference in 2- and 5-year OS between 5-Aza and BSC arms.
Difference in changes in QoL from diagnosis in both arms
Difference in number and duration of hospitalizations in both
arms in the 2 years post-remission
QOL-ESS AZA AMLE TRIAL:
Design – Prospective randomized trial
Elderly AML patients undergoing IC reaching a CR are randomized to receive post-remission
azacitidine or best supportive care
QoLESS AZA-AMLE
Objectives
22. Ist 3+7 induction cycle
2nd 3+7 induction
cycle
Consolidation
Randomization
Off-protocol
CR or PR
CR
CR
NR
PR/Resistance/
Relapse
Relapse
A
M
L
D
I
A
G
N
O
S
I
S
BSC vs 5-Azacitidine
1:1
QOLESS-AZA-AMLE: Study design
3+7= daunorubicin 40mg/m2 daily on days 1–3
+ cytarabine 100mg/m2 daily as a continuous IV infusion on days 1–7
Consolidation = 3-hour infusion of cytarabine 800mg/m2 BID on days 1–3
BSC = best supportive care; NR= no remission; PR = partial remission
Oliva et al. ASH 2015 poster presentation
Q
O
L
A
S
S
E
S
S
M
E
N
T
QOL ASSESSMENT
QOL ASSESSMENT
23. Oliva et al. ASH 2015 poster presentation
Characteristics of patients at diagnosis
24. QoL at diagnosis and correlations with hemoglobin
Factors not associated with QoL:
PLT, leukocytes, blasts, ECOG PS, de novo/secondary, Charlson comorbidity index
Oliva et al. ASH 2015 poster presentation
25. Oliva et al. ASH 2015 poster presentation
Changes in QoL after induction chemotherapy
26. Oliva et al. ASH 2015 poster presentation
Changes in QoL after consolidation in patients in CR
27. Changes in QoL according to QoL at diagnosis
Oliva et al. ASH 2015 poster presentation
improvement deterioration
28. Changes in symptoms according to intensity of
symptoms at diagnosis
Oliva et al. ASH 2015 poster presentation
29. Oliva et al. ASH 2015 poster presentation
Baseline role function according to response
30. QOL-ESS AZA AMLE TRIAL:
Impact of post-remission on AML free survival (1st interim analysis)
QoLESS AZA-AMLE
Oliva et al. ASH 2014 poster presentation
33. Response
TC
Decitabine
(n = 242)
Supportive
Care (n = 28)
Cytarabine
(n = 215)
Total TC
(n = 243)
No. % No. % No. % No. %
CR 1 3.6 17 7.9 18 7.4 38 15.7
CRi 1 3.6 6 2.8 7 2.9 24 9.9
CRp 0 0 1 0.5 1 0.4 5 2.1
CR + CRp 1 3.6 18 8.4 19 7.8* 43 17.8*
Partial remission 1 3.6 8 3.7 9 3.7 6 2.5
Stable disease 3 10.7 52 24.2 55 22.6 67 27.7
Progressive disease 10 35.7 69 32.1 79 32.5 50 20.7
Not evaluable 12 42.9 63 29.3 75 30.9 57 23.6
Kantarjian H M et al. JCO 2012;30:2670-2677
CR, complete remission; CRi, CR with incomplete blood count recovery;
CRp, CR with incomplete platelet recovery; TC, treatment choice.
Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice,
With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the
Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia
34. Overall survival in a protocol-specified 2009 clinical cut-off analysis of decitabine and
treatment choice (TC) in the intent-to-treat population.
Kantarjian H M et al. JCO 2012;30:2670-2677
No difference in median OS with decitabine (7.7 months;
95% CI, 6.2 to 9.2 months) versus TC (5.0 months; 95% CI,
4.3 to 6.3 months).
The estimated HR for death (decitabine:TC) was 0.85 (95%
CI, 0.69 to 1.04).
At the mature analysis (2010 cutoff), 446 deaths
(92.0%) were reported (decitabine, n = 219; TC, n =
227).
Median OS values were the same, but differences
reached significance.
36. 36
488 Patients Enrolled
Investigator Preselection
LDAC
n=312 (64%)
IC
n=87 (18%)
BSC Only
n=89 (18%)
AZA
n=44
Randomisation
BSC
n=45
AZA
n=154
LDAC
n=158
AZA
n=43
IC
n=44
AZA-AML-001 trial – elderly AML patients > 30% blasts
Dombret H, et al. Blood 2015, Vol 126, 3.
Multicenter, randomized trial – azacitidine (AZA) versus other physician preselected
conventional treatment (CCR)
BSC = best supportive care
LDAC = low dose cytarabine
IC = intensive chemoherapy
37. *Stratified by ECOG PS and cytogenetic risk; ITT = intention to treat
AZA = azacitidine; CCR = preselected conventional chemotherapy regimen
Median follow-up: 24.4 months
40
AZA (n=241)
CCR (n=247)
0
0.2
0.4
0.6
0.8
1.0
0 4 8 12 16 20 24 28 32 36
Time from randomisation, months
10.4 months
6.5 months Stratified:* p=0.101
Overall survival - AZA versus CCR
Probabilityofsurvival
1-year OS: AZA 46.5%; CCR 34.2% (95% CI: 3.5%, 21.0%)
Dombret H, et al. Blood 2015, Vol 126, 3.
38. OS in patients treated with AZA vs the individual
components of the CCR arm*
*not powered to detect statistical differences between AZA and the individual components of the CCR arm
30.3 18.61-yr OS (%) 48.5 34.0 55.8 50.9
Patients (n) 44 45 154 158 43 44
Azacitidine
CCR
0
2
4
6
8
10
12
BSC
(n=89)
LDAC
(n=312)
IC
(n=87)
MedianOS,
months
5.8
3.7
11.2
6.4
13.3
12.2
14
“Median OS was higher with AZA versus BSC, and was similar to that with LDAC and IC“
Dombret H, et al. Blood 2015, Vol 126, 3.
p=0.0288
p=0.4270
p=0.5032
40. Rates of RBC-TI and PLT-TI in patients who were
TD at baseline
38,5
40,6
27,6
29,3
0
5
10
15
20
25
30
35
40
45
RBC-TI Platelet-TI
Patients,%
Azacitidine
CCR
PLT = platelet; RBC = red blood cell
TD = transfusion dependent; TI = transfusion independent
“Higher proportions of patients who were TD at baseline attained RBC-TI or platelet-TI with AZA vs CCR.
Furthermore, the proportions of patients who remained or became RBC-TI or platelet-TI were higher with AZA.”
Dombret H, et al. Blood 2015, Vol 126, 3.
41. Post hoc analysis of survival in patients who did
not achieve CR
33,8
20,4
0
5
10
15
20
25
30
35
40
AZA CCR
1-yearOS,%
∆13.4% (95% CI: 4.5%, 22.4%)
6,9
4,2
0
1
2
3
4
5
6
7
8
AZA CCR
MedianOS,months
Stratified log-rank p=0.0170
Median OS 1-year OS
Dombret H, et al. Blood 2015, Vol 126, 3.
42. TEAE, % AZA (n=236) LDAC (n=153) IC (n=42)
Nausea 27.1 22.2 42.9
Neutropenia 19.9 22.9 31.0
Thrombocytopenia 17.4 22.2 21.4
Febrile neutropenia 14.8 20.3 31.0
Vomiting 14.4 10.5 7.1
Decreased appetite 13.6 9.2 11.9
Constipation 13.1 6.5 11.9
Injection site reaction 12.7 0 0
Pyrexia 13.2 15.7 23.8
Diarrhoea 12.3 5.2 21.4
Injection site erythema 11.9 0 0
Anaemia 7.6 13.7 14.3
Leukopenia 7.2 8.5 14.3
Hypokalaemia 1.7 3.9 11.9
Oral herpes 0.8 2.0 11.9
Most frequent drug-related TEAEs† in patients
treated with AZA versus LDAC or IC‡
†Coded using MedDRA and graded according to CTCAE v4.0 criteria
‡These data are not adjusted for duration of drug exposure
Dombret H, et al. Blood 2015, Vol 126, 3.
43. 0
5
10
15
20
25
Cycles 1–2 Cycles 3–4 Cycles 5–6
Patients,%
Febrile neutropenia Neutropenia Thrombocytopenia Anaemia
Incidence of haematological TEAEs* (any grade)
by cycle in patients treated with AZA†
*Coded using MedDRA and graded according to CTCAE v4.0 criteria
†These data are not adjusted for duration of drug exposure
Dombret H, et al. Blood 2015, Vol 126, 3.
44. Rates of hospitalisation and time spent in hospital
due to TEAEs per patient-year of drug exposure
1,96
2,39
0
1
2
3
Hospitalisation
due to TEAEs
Perpatient-yearof
treatmentexposure
28,5
38,3
0
10
20
30
40
50
Time spent in hospital due
to TEAEsDaysperpatient-yearof
treatmentexposure
Azacitidine CCR
p=0.0083 p<0.0001
Rates of hospitalisation due to TEAEs Time spent in hospital due to TEAEs
Dombret H, et al. Blood 2015, Vol 126, 3.
45. • No meaningful deterioration from baseline
was observed with AZA or CCR in the 4
domains through cycle 9
• Few changes were statistically significant
(p<0.05) and fewer met the MID threshold
– Patients receiving CCR achieved meaningful
improvement in Fatigue at cycles 7 and 9 and in
Global Health Status/QoL at cycle 9
• Multivariate MMRM analysis showed no
significant differences between AZA and
CCR in the 4 preselected domains, except
for Fatigue in favor of CCR (p=0.04);
however, the difference was no longer
significant after controlling for receipt RBC
transfusions within 5 days of HRQL
assessment (p=0.09)
Decreasing scores indicate improvement in the Fatigue and Dyspnea domains and increasing
scores indicate improvement in the Physical Function and Global Health Status/QoL domains
*Met the threshold for minimally important difference (MID)
-15
-10
-5
0
5
10
15
Cycle 3 Cycle 5 Cycle 7 Cycle 9
Mean Change v. Baseline AZA vs. CCR
Fatigue & Dyspnea
Fatigue- AZA Dsypnea- AZA
Fatigue- CCR Dyspnea- CCR
-15
-10
-5
0
5
10
15
Cycle 3 Cycle 5 Cycle 7 Cycle 9
Mean Change v. Baseline AZA vs. CCR
Physical Functioning & Global Health/QoL
Physical Functioning- AZA Global Health/ QoL- AZA
Physical Functioning- CCR Global Health/ QoL- CCR
ImprovementImprovement
* *
*
Results – Quality of life Outcomes: AZA vs CCR
Minden et al. Poster P184 EHA 2015
46. • Within the LDAC preselection group, HRQL
outcomes with AZA (n=102) and LDAC
(n=95) were largely consistent with the
primary HRQL analysis
• Patients randomized to AZA achieved
meaningful improvement in the Fatigue &
Global Health Status/QoL domains at cycle
9
Decreasing scores indicate improvement in the Fatigue and Dyspnea domains
of the QLQ-C30, and increasing scores indicate improvement in the Physical
Function and Global Health Status/QoL domains
*Met the threshold for minimally important difference (MID)
-15
-10
-5
0
5
10
15
Cycle 3 Cycle 5 Cycle 7 Cycle 9
Mean Change v. Baseline AZA vs. LDC
Post-Hoc Analysis of Patients Pre-Selected to LDC
Physical Functioning- AZA Global Health- AZA
Physical Functioning- LDC Global Health- LDC
ImprovementImprovement
*
*
-15
-10
-5
0
5
10
15
Cycle 3 Cycle 5 Cycle 7 Cycle 9
Mean Change v. Baseline AZA vs. LDC
Post-Hoc Analysis of Patients Pre-Selected to LDC
Fatigue- AZA Dyspnea- AZA
Fatigue- LDC Dyspnea- LDC
Minden et al. Poster P184 EHA 2015
Results – Quality of Life Outcomes in Patients
Preselected to Receive LDAC
47. Defining response to treatment:
ELN response criteria in AML
Category Definition (no minimum duration of response required)
CR BM blasts <5%; absence of blasts with Auer rods; absence of EMD; absolute
neutrophil count >1.0 x 109/L; platelet count >100 x 109/L; RBC-TI
CR with incomplete
recovery (CRi)
All CR criteria except for residual neutropenia (<1.0 x 109/L) or
thrombocytopenia (<100 x 109/L)
Morphological leukaemia-
free state
BM blasts <5%; absence of blasts with Auer rods; absence of EMD; no
haematological recovery required
PR Relevant in the setting of phase I and II clinical trials only; all haematological
criteria of CR required with decrease of at least 50% in the percentage of BM
blasts to a value between 5–25%
Cytogenetic CR (CRc) Reversion to a normal karyotype at the time of morphologic CR (or CRi) in cases
with an abnormal karyotype at the time of diagnosis; based on the evaluation of
20 metaphase cells from BM
Molecular CR (CRm) No standard definition; depends on molecular target
Dohner H, et al. Blood 2010;115:453–74
Definitions of response based primarily on IWG criteria
ELN = European LeukemiaNet
48. Defining treatment failure: ELN response criteria
in AML
Category Definition
Resistant disease (RD) Failure to achieve CR or CRi (general practice; phase II–III trials), or failure to
achieve CR, CRi, or PR (phase I trials)
Only includes patients surviving ≥7 days following completion of initial treatment,
with evidence of persistent leukaemia by blood and/or BM examination
Death in aplasia Deaths occurring ≥7 days following completion of initial treatment while patient
has cytopenias; with an aplastic or hypoplastic BM obtained within 7 days of
death, without evidence of persistent leukaemia
Death from indeterminate
cause
Deaths occurring before completion of therapy, or <7 days following its
completion
Deaths occurring ≥7 days following completion of initial therapy with no blasts in
the blood, but no BM examination available
Relapse BM blasts ≥5%; or reappearance of blasts in the blood; or development of EMD
Dohner H, et al. Blood 2010;115:453–74
49. Defining haematological improvement:
IWG response criteria in MDS
Category Definition (response must be maintained for ≥8 weeks)
Erythroid response (pre-
treatment Hb <11g/dL)
≥1.5g/dL increase in Hb; reduction in transfusion frequency of ≥4 transfusions/8
weeks compared with the 8 weeks prior to treatment (pre-treatment transfusions
are only counted if given for Hb of ≤9g/dL)
Platelet response
(pre-treatment platelet count
<100 Χ 109/L)
Absolute increase of ≥30 Χ 109/L for patients with a pre-treatment platelet count
of >20 x 109/L
Increase from <20 x 109/L to >20 x 109/L and by at least 100%
Neutrophil response
(pre-treatment ANC
<1.0 Χ 109/L)
At least 100% increase in ANC and an ANC of
>0.5 x 109/L
Cheson BD, et al. Blood 2006;108:419–25