The document summarizes key aspects of diffuse large B-cell lymphoma (DLBCL), including that it is the most common aggressive lymphoma accounting for 30% of cases. The median age at diagnosis is 70 years, with 50-60% of patients cured with first-line chemoimmunotherapy. However, treatment leads to substantial toxicity and morbidity. Relapsed or refractory disease typically occurs within 2 years and has treatment options including more intensive chemotherapy, CAR T-cell therapy, or experimental therapies. Certain genetic alterations and biomarkers are associated with worse prognosis.
This document summarizes the use of PET-CT in staging and assessing treatment response in Hodgkin's lymphoma. It discusses that PET-CT is an important tool for initial staging, assessing response to chemotherapy, and prognostic indicator when done after partial chemotherapy. The sensitivity and specificity of PET-CT is higher than CT alone for detecting nodal and organ involvement. PET-CT may avoid the need for bone marrow biopsy in some cases. Interim PET imaging helps distinguish residual mass as viable tumor or necrosis/fibrosis. The document also reviews chemotherapy regimens like ABVD, BEACOPP and Stanford V in early and advanced Hodgkin's lymphoma.
Management of tuberculosis in special situation and MDR TB.NUR PUNAM
This document discusses tuberculosis (TB) and drug-induced liver injury (DILI) from TB treatment. It provides statistics on TB prevalence and mortality worldwide. It then outlines various diagnostic tests for TB and risk factors for DILI. The document discusses guidelines for managing DILI and approaches to treating different patient populations like those with HIV, liver disease, pregnancy, etc. It addresses strategies for treating multidrug resistant TB and monitoring patients on second line drugs.
Ruxolitinib is an oral inhibitor of JAK1 and JAK2 that is effective for treating polycythemia vera in patients who have an inadequate response or intolerance to hydroxyurea. It reduces hematocrit and spleen size while improving symptoms. In clinical trials, ruxolitinib provided durable control of hematocrit without phlebotomy and significantly reduced spleen volume compared to best available therapies. The most common side effects were mild and included headache, diarrhea, and fatigue.
This document provides an overview and update on anti-tuberculosis therapy. It begins by outlining the objectives of becoming familiar with first and second line anti-tuberculosis drugs, their treatment regimens, adverse effects and drug interactions. It then reviews the standard first line treatment regimen of 2HRZE/4HR, describes the common first line drugs isoniazid, rifampin and ethambutol and their adverse effects. It also briefly discusses second line drugs and treatment in special populations before concluding with a review of multi-drug resistant tuberculosis and second line treatment options.
Autoimmune hepatitis is a chronic liver disease characterized by autoimmune destruction of the liver. It is diagnosed based on the presence of autoantibodies, elevated serum globulins, and evidence of hepatitis on liver biopsy after excluding other causes. The disease affects women more than men and can progress to cirrhosis if untreated. Treatment involves immunosuppression with corticosteroids and azathioprine to induce and maintain remission.
Harry P. Erba, MD, PhD, Naval Daver, MD, Courtney D. DiNardo, MD, MSCE, and Gail J. Roboz, MD prepared useful Practice Aids pertaining to acute myeloid leukemia for this CME/MOC activity titled Transforming Modern Care in AML: Clinical Solutions With Novel Agents for Diverse Patient Populations. For the full presentation, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3fsa7Jh. CME/MOC credit will be available until July 9, 2021.
Cyclosporine is an immunosuppressive drug that was originally isolated from fungi in 1970 and approved by the FDA for transplant rejection in 1983. It is a cyclic polypeptide consisting of 11 amino acids that acts by inhibiting T cell activation through the calcineurin/NFAT pathway. It has since been approved for treating various dermatological conditions like psoriasis, atopic dermatitis, and pyoderma gangrenosum. While effective, cyclosporine use can cause nephrotoxicity, hypertension, and increased risk of infection and skin cancer with long term use. It can also interact with various other drugs that are metabolized through the CYP3A4 pathway.
This document provides information on rheumatoid arthritis (RA) including its pathophysiology, epidemiology, clinical features, and treatment with disease-modifying antirheumatic drugs (DMARDs). RA is a chronic inflammatory disease that causes peripheral polyarthritis. Treatment involves non-biological DMARDs like methotrexate and sulfasalazine as well as biological DMARDs that target cytokines like TNF-α. Biological agents have improved treatment outcomes for RA by reducing joint damage and disability.
This document summarizes the use of PET-CT in staging and assessing treatment response in Hodgkin's lymphoma. It discusses that PET-CT is an important tool for initial staging, assessing response to chemotherapy, and prognostic indicator when done after partial chemotherapy. The sensitivity and specificity of PET-CT is higher than CT alone for detecting nodal and organ involvement. PET-CT may avoid the need for bone marrow biopsy in some cases. Interim PET imaging helps distinguish residual mass as viable tumor or necrosis/fibrosis. The document also reviews chemotherapy regimens like ABVD, BEACOPP and Stanford V in early and advanced Hodgkin's lymphoma.
Management of tuberculosis in special situation and MDR TB.NUR PUNAM
This document discusses tuberculosis (TB) and drug-induced liver injury (DILI) from TB treatment. It provides statistics on TB prevalence and mortality worldwide. It then outlines various diagnostic tests for TB and risk factors for DILI. The document discusses guidelines for managing DILI and approaches to treating different patient populations like those with HIV, liver disease, pregnancy, etc. It addresses strategies for treating multidrug resistant TB and monitoring patients on second line drugs.
Ruxolitinib is an oral inhibitor of JAK1 and JAK2 that is effective for treating polycythemia vera in patients who have an inadequate response or intolerance to hydroxyurea. It reduces hematocrit and spleen size while improving symptoms. In clinical trials, ruxolitinib provided durable control of hematocrit without phlebotomy and significantly reduced spleen volume compared to best available therapies. The most common side effects were mild and included headache, diarrhea, and fatigue.
This document provides an overview and update on anti-tuberculosis therapy. It begins by outlining the objectives of becoming familiar with first and second line anti-tuberculosis drugs, their treatment regimens, adverse effects and drug interactions. It then reviews the standard first line treatment regimen of 2HRZE/4HR, describes the common first line drugs isoniazid, rifampin and ethambutol and their adverse effects. It also briefly discusses second line drugs and treatment in special populations before concluding with a review of multi-drug resistant tuberculosis and second line treatment options.
Autoimmune hepatitis is a chronic liver disease characterized by autoimmune destruction of the liver. It is diagnosed based on the presence of autoantibodies, elevated serum globulins, and evidence of hepatitis on liver biopsy after excluding other causes. The disease affects women more than men and can progress to cirrhosis if untreated. Treatment involves immunosuppression with corticosteroids and azathioprine to induce and maintain remission.
Harry P. Erba, MD, PhD, Naval Daver, MD, Courtney D. DiNardo, MD, MSCE, and Gail J. Roboz, MD prepared useful Practice Aids pertaining to acute myeloid leukemia for this CME/MOC activity titled Transforming Modern Care in AML: Clinical Solutions With Novel Agents for Diverse Patient Populations. For the full presentation, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3fsa7Jh. CME/MOC credit will be available until July 9, 2021.
Cyclosporine is an immunosuppressive drug that was originally isolated from fungi in 1970 and approved by the FDA for transplant rejection in 1983. It is a cyclic polypeptide consisting of 11 amino acids that acts by inhibiting T cell activation through the calcineurin/NFAT pathway. It has since been approved for treating various dermatological conditions like psoriasis, atopic dermatitis, and pyoderma gangrenosum. While effective, cyclosporine use can cause nephrotoxicity, hypertension, and increased risk of infection and skin cancer with long term use. It can also interact with various other drugs that are metabolized through the CYP3A4 pathway.
This document provides information on rheumatoid arthritis (RA) including its pathophysiology, epidemiology, clinical features, and treatment with disease-modifying antirheumatic drugs (DMARDs). RA is a chronic inflammatory disease that causes peripheral polyarthritis. Treatment involves non-biological DMARDs like methotrexate and sulfasalazine as well as biological DMARDs that target cytokines like TNF-α. Biological agents have improved treatment outcomes for RA by reducing joint damage and disability.
Alexander Perl, MD, and James M. Foran, MD, FRCPC, prepared useful practice aids pertaining to leukemia for this CME activity titled "Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2EZE2I6. CME credit will be available until March 28, 2020.
Prompt treatment of active tuberculosis is key to preventing its spread. There are several treatment options that involve combinations of drugs like isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin over initial and continuation phases. Close monitoring is important due to potential adverse effects of the drugs that can impact the liver, vision or hearing. Local public health departments play an important role in treatment by arranging direct observation of therapy and follow-up care for tuberculosis patients.
The document provides guidance on treating hepatitis C, defining sustained virologic response, identifying appropriate treatment candidates, and differentiating treatment by genotype. It discusses factors that affect treatment response, common side effects of treatment medications like peginterferon and ribavirin, and screening and monitoring processes during treatment. The future of hepatitis C treatment involves adding protease inhibitors telaprevir or boceprevir to peginterferon and ribavirin regimens.
Harry P. Erba, MD, PhD, and James M. Foran, MD, FRCPC, prepared useful Practice Aids pertaining to acute myeloid leukemia for this CME activity titled "The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2vdoO1j. CME credit will be available until March 12, 2021.
Lapatinib is a tyrosine kinase inhibitor that reversibly binds to EGFR and HER2, blocking phosphorylation. It is used in combination with capecitabine for advanced/metastatic HER2+ breast cancer and with letrozole for HER2+/HR+ disease. It has good CNS penetration and may prevent brain metastases. Clinical trials showed combination with trastuzumab increased pCR rates over monotherapy. Common side effects include diarrhea, rash, fatigue. Dose reductions are needed for severe hepatic or cardiac toxicity.
This document discusses complications of peritoneal dialysis (PD) therapy, including infectious and non-infectious complications. It provides guidance on diagnosing and treating peritonitis, the major infectious complication of PD. It recommends empiric antibiotic therapy for peritonitis including cefazolin/cephalothin and vancomycin or teicoplanin initially. Therapy should be adjusted based on culture results and patient response. Non-infectious complications discussed include mechanical issues like pain or hernias as well as metabolic disturbances like ultrafiltration failure or encapsulating peritoneal sclerosis. Overall the document provides clinical guidelines for managing common complications of peritoneal dialysis.
1. The document discusses the management of tuberculosis, including the history, statistics, principles of treatment, protocols, side effects of drugs, and the Revised National Tuberculosis Control Programme in India.
2. It covers topics like tuberculosis and diabetes, tuberculosis and HIV co-infection, multi-drug resistant tuberculosis, and paradoxical reactions seen with antituberculosis treatment and antiretroviral therapy.
3. Guidelines are provided for treatment of different categories of tuberculosis patients, management of drug interactions and adverse effects, and regimens for multi-drug resistant cases.
1. Tuberculosis remains a major global health problem, with an estimated 2 billion people infected and 10 million new active cases each year resulting in 1.5 million deaths.
2. Standard short course DOTS therapy involves a combination of drugs administered over 6-9 months depending on the category of TB. Adverse effects of the main anti-TB drugs are discussed.
3. Multidrug resistant TB and extensively drug resistant TB present significant treatment challenges, requiring prolonged courses of second-line drugs and close monitoring given their increased toxicity. Preventing further emergence of drug resistance is critical.
Colorectal cancer - adjuvant Rx - Nicola Tannerwelshbarbers
This document discusses treatment principles for colorectal cancer including histological staging, chemotherapy, surgery, and trials. It covers adjuvant therapies for colon and rectal cancers including chemotherapy with or without radiotherapy. It also discusses neoadjuvant treatments and timelines for administering adjuvant therapies. Key points covered include Dukes staging, 5-year survival rates by stage, aims of adjuvant therapy, and common surgeries for colon and rectal cancers.
This document summarizes guidelines and treatment recommendations for prostate cancer management. It discusses risk stratification and different treatment options including active surveillance, surgery, radiation therapy using brachytherapy or external beam radiation, and androgen deprivation therapy. Treatment selection is based on patient life expectancy, tumor characteristics, and availability of local therapies. Side effects of different treatments are also reviewed.
This document discusses thrombotic microangiopathy (TMA) that occurs after hematopoietic stem cell transplantation (HSCT), known as transplant-associated TMA (TA-TMA). TA-TMA has a high mortality rate and current treatments are suboptimal. The diagnosis of TA-TMA is challenging as it does not clearly fall under typical TMA categories and has normal ADAMTS13 levels. While plasma exchange is often used, its efficacy is unclear. Complement blocking with eculizumab may be a more effective treatment, with one study finding it improved 1-year survival from 9% to 62% compared to other therapies.
Harry P. Erba, MD, PhD prepared useful practice aids pertaining to acute myeloid leukemia for this CME/MOC activity titled "Advances in AML Care: Highlights From Recent Science." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/2Xsu5x1. CME/MOC credit will be available until June 15, 2021.
Onali S. IBD: Cosa è cambiato nella Terapia. ASMaD 2013Gianfranco Tammaro
1. The document discusses inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. It covers epidemiology, pathophysiology, clinical presentation, goals of treatment, and current treatment options.
2. Key points include that immunosuppressors like azathioprine and 6-mercaptopurine are effective for long-term maintenance of remission, while biologics like infliximab are rapidly effective but their use is expanding.
3. Achieving mucosal healing is an important new treatment goal, especially in ulcerative colitis, as it predicts sustained clinical remission. Management must be tailored to each individual patient based on their disease characteristics and needs.
cancer associated thrombocytopenia.pptxMarwa Khalifa
This document discusses chemotherapy-induced thrombocytopenia (CIT), which is common in cancer patients undergoing chemotherapy. It outlines the mechanisms and risk factors for CIT and challenges in managing it. Current approaches to treating CIT include platelet transfusions and thrombopoietic agents like recombinant human interleukin-11 and thrombopoietin receptor agonists like romiplostim and eltrombopag. While not FDA-approved for CIT, studies have found these agents can increase platelet counts, reduce transfusions, and allow maintenance of full chemotherapy doses with minimal side effects. The document concludes that thrombopoietin receptor agonists should be considered for patients who cannot be supported by transfusions to maintain chemotherapy dose intensity crucial
This document summarizes several studies on immunotherapy for ovarian cancer. It finds that the presence of tumor infiltrating lymphocytes (TILs) predicts better prognosis. Anti-PD-1/PD-L1 therapies such as nivolumab, pembrolizumab, and avelumab have shown response rates of 11.5-17% in ovarian cancer. Combining PARP inhibitors with immunotherapy may increase response rates to 45% in patients with BRCA mutations. Ongoing studies are combining anti-angiogenic therapies like bevacizumab with immunotherapies and exploring these combinations as adjuvant therapies or in platinum-resistant disease.
This document summarizes information about autoimmune hepatitis (AIH), including:
- It is a T-cell mediated immune attack on the liver that causes progressive damage and can lead to cirrhosis.
- Two main types (type 1 and type 2) are distinguished by their associated autoantibodies.
- Women are affected more often than men. Treatment involves immunosuppression with glucocorticoids alone or in combination with azathioprine to induce remission. Response to treatment and long term outcomes depend on disease severity at presentation.
Ghassan Abou-Alfa, MD, MBA, Anthony El-Khoueiry, MD, and R. Kate Kelley, MD, prepared useful Practice Aids pertaining to liver cancer for this CME/CE activity titled "Teaming Up to Improve Outcomes in Advanced Hepatocellular Carcinoma: A Tumor Board Evaluating the Potential of Immunotherapy and Novel Targeted Approaches." For the full presentation, monograph, complete CME/CE information, and to apply for credit, please visit us at http://bit.ly/2FG0J75. CME/CE credit will be available until March 25, 2019.
This document discusses various anti-tubercular drugs used to treat tuberculosis. It describes the classification of first-line drugs which include isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin. It also discusses second-line drugs including para-amino salicylic acid, ethionamide, cycloserine, thiacetazone, fluoroquinolones and macrolides. For each drug, it provides information on mechanisms of action, pharmacokinetics, dosing, adverse effects and drug interactions. The document is intended as an educational reference on anti-tubercular medications.
Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Asso...Raj Kiran Medapalli
This document summarizes a study that compared pulse cyclophosphamide (IV or oral) given every 2-3 weeks to daily oral cyclophosphamide for inducing remission in ANCA-associated vasculitis. The study was a randomized controlled trial involving 149 patients across multiple centers. Both groups also received tapering doses of prednisone. The primary goal was to evaluate if pulse cyclophosphamide was as effective as daily treatment, but with fewer side effects due to the lower cumulative dose. Outcomes such as remission rates, adverse events, and relapse rates were compared between the two groups.
ATT induced liver injury is very common with anti tubercular drugs as tuberculosis is one of the most common infection in india. Management of att liver injury is very important in medicine and is elaborated here.
Fexofenadine is sold under the brand name Allegra.
It is a selective peripheral H1 blocker. It is classified as a second-generation antihistamine because it is less able to pass the blood–brain barrier and causes lesser sedation, as compared to first-generation antihistamines.
It is on the World Health Organization's List of Essential Medicines. Fexofenadine has been manufactured in generic form since 2011.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Alexander Perl, MD, and James M. Foran, MD, FRCPC, prepared useful practice aids pertaining to leukemia for this CME activity titled "Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2EZE2I6. CME credit will be available until March 28, 2020.
Prompt treatment of active tuberculosis is key to preventing its spread. There are several treatment options that involve combinations of drugs like isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin over initial and continuation phases. Close monitoring is important due to potential adverse effects of the drugs that can impact the liver, vision or hearing. Local public health departments play an important role in treatment by arranging direct observation of therapy and follow-up care for tuberculosis patients.
The document provides guidance on treating hepatitis C, defining sustained virologic response, identifying appropriate treatment candidates, and differentiating treatment by genotype. It discusses factors that affect treatment response, common side effects of treatment medications like peginterferon and ribavirin, and screening and monitoring processes during treatment. The future of hepatitis C treatment involves adding protease inhibitors telaprevir or boceprevir to peginterferon and ribavirin regimens.
Harry P. Erba, MD, PhD, and James M. Foran, MD, FRCPC, prepared useful Practice Aids pertaining to acute myeloid leukemia for this CME activity titled "The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2vdoO1j. CME credit will be available until March 12, 2021.
Lapatinib is a tyrosine kinase inhibitor that reversibly binds to EGFR and HER2, blocking phosphorylation. It is used in combination with capecitabine for advanced/metastatic HER2+ breast cancer and with letrozole for HER2+/HR+ disease. It has good CNS penetration and may prevent brain metastases. Clinical trials showed combination with trastuzumab increased pCR rates over monotherapy. Common side effects include diarrhea, rash, fatigue. Dose reductions are needed for severe hepatic or cardiac toxicity.
This document discusses complications of peritoneal dialysis (PD) therapy, including infectious and non-infectious complications. It provides guidance on diagnosing and treating peritonitis, the major infectious complication of PD. It recommends empiric antibiotic therapy for peritonitis including cefazolin/cephalothin and vancomycin or teicoplanin initially. Therapy should be adjusted based on culture results and patient response. Non-infectious complications discussed include mechanical issues like pain or hernias as well as metabolic disturbances like ultrafiltration failure or encapsulating peritoneal sclerosis. Overall the document provides clinical guidelines for managing common complications of peritoneal dialysis.
1. The document discusses the management of tuberculosis, including the history, statistics, principles of treatment, protocols, side effects of drugs, and the Revised National Tuberculosis Control Programme in India.
2. It covers topics like tuberculosis and diabetes, tuberculosis and HIV co-infection, multi-drug resistant tuberculosis, and paradoxical reactions seen with antituberculosis treatment and antiretroviral therapy.
3. Guidelines are provided for treatment of different categories of tuberculosis patients, management of drug interactions and adverse effects, and regimens for multi-drug resistant cases.
1. Tuberculosis remains a major global health problem, with an estimated 2 billion people infected and 10 million new active cases each year resulting in 1.5 million deaths.
2. Standard short course DOTS therapy involves a combination of drugs administered over 6-9 months depending on the category of TB. Adverse effects of the main anti-TB drugs are discussed.
3. Multidrug resistant TB and extensively drug resistant TB present significant treatment challenges, requiring prolonged courses of second-line drugs and close monitoring given their increased toxicity. Preventing further emergence of drug resistance is critical.
Colorectal cancer - adjuvant Rx - Nicola Tannerwelshbarbers
This document discusses treatment principles for colorectal cancer including histological staging, chemotherapy, surgery, and trials. It covers adjuvant therapies for colon and rectal cancers including chemotherapy with or without radiotherapy. It also discusses neoadjuvant treatments and timelines for administering adjuvant therapies. Key points covered include Dukes staging, 5-year survival rates by stage, aims of adjuvant therapy, and common surgeries for colon and rectal cancers.
This document summarizes guidelines and treatment recommendations for prostate cancer management. It discusses risk stratification and different treatment options including active surveillance, surgery, radiation therapy using brachytherapy or external beam radiation, and androgen deprivation therapy. Treatment selection is based on patient life expectancy, tumor characteristics, and availability of local therapies. Side effects of different treatments are also reviewed.
This document discusses thrombotic microangiopathy (TMA) that occurs after hematopoietic stem cell transplantation (HSCT), known as transplant-associated TMA (TA-TMA). TA-TMA has a high mortality rate and current treatments are suboptimal. The diagnosis of TA-TMA is challenging as it does not clearly fall under typical TMA categories and has normal ADAMTS13 levels. While plasma exchange is often used, its efficacy is unclear. Complement blocking with eculizumab may be a more effective treatment, with one study finding it improved 1-year survival from 9% to 62% compared to other therapies.
Harry P. Erba, MD, PhD prepared useful practice aids pertaining to acute myeloid leukemia for this CME/MOC activity titled "Advances in AML Care: Highlights From Recent Science." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/2Xsu5x1. CME/MOC credit will be available until June 15, 2021.
Onali S. IBD: Cosa è cambiato nella Terapia. ASMaD 2013Gianfranco Tammaro
1. The document discusses inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. It covers epidemiology, pathophysiology, clinical presentation, goals of treatment, and current treatment options.
2. Key points include that immunosuppressors like azathioprine and 6-mercaptopurine are effective for long-term maintenance of remission, while biologics like infliximab are rapidly effective but their use is expanding.
3. Achieving mucosal healing is an important new treatment goal, especially in ulcerative colitis, as it predicts sustained clinical remission. Management must be tailored to each individual patient based on their disease characteristics and needs.
cancer associated thrombocytopenia.pptxMarwa Khalifa
This document discusses chemotherapy-induced thrombocytopenia (CIT), which is common in cancer patients undergoing chemotherapy. It outlines the mechanisms and risk factors for CIT and challenges in managing it. Current approaches to treating CIT include platelet transfusions and thrombopoietic agents like recombinant human interleukin-11 and thrombopoietin receptor agonists like romiplostim and eltrombopag. While not FDA-approved for CIT, studies have found these agents can increase platelet counts, reduce transfusions, and allow maintenance of full chemotherapy doses with minimal side effects. The document concludes that thrombopoietin receptor agonists should be considered for patients who cannot be supported by transfusions to maintain chemotherapy dose intensity crucial
This document summarizes several studies on immunotherapy for ovarian cancer. It finds that the presence of tumor infiltrating lymphocytes (TILs) predicts better prognosis. Anti-PD-1/PD-L1 therapies such as nivolumab, pembrolizumab, and avelumab have shown response rates of 11.5-17% in ovarian cancer. Combining PARP inhibitors with immunotherapy may increase response rates to 45% in patients with BRCA mutations. Ongoing studies are combining anti-angiogenic therapies like bevacizumab with immunotherapies and exploring these combinations as adjuvant therapies or in platinum-resistant disease.
This document summarizes information about autoimmune hepatitis (AIH), including:
- It is a T-cell mediated immune attack on the liver that causes progressive damage and can lead to cirrhosis.
- Two main types (type 1 and type 2) are distinguished by their associated autoantibodies.
- Women are affected more often than men. Treatment involves immunosuppression with glucocorticoids alone or in combination with azathioprine to induce remission. Response to treatment and long term outcomes depend on disease severity at presentation.
Ghassan Abou-Alfa, MD, MBA, Anthony El-Khoueiry, MD, and R. Kate Kelley, MD, prepared useful Practice Aids pertaining to liver cancer for this CME/CE activity titled "Teaming Up to Improve Outcomes in Advanced Hepatocellular Carcinoma: A Tumor Board Evaluating the Potential of Immunotherapy and Novel Targeted Approaches." For the full presentation, monograph, complete CME/CE information, and to apply for credit, please visit us at http://bit.ly/2FG0J75. CME/CE credit will be available until March 25, 2019.
This document discusses various anti-tubercular drugs used to treat tuberculosis. It describes the classification of first-line drugs which include isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin. It also discusses second-line drugs including para-amino salicylic acid, ethionamide, cycloserine, thiacetazone, fluoroquinolones and macrolides. For each drug, it provides information on mechanisms of action, pharmacokinetics, dosing, adverse effects and drug interactions. The document is intended as an educational reference on anti-tubercular medications.
Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Asso...Raj Kiran Medapalli
This document summarizes a study that compared pulse cyclophosphamide (IV or oral) given every 2-3 weeks to daily oral cyclophosphamide for inducing remission in ANCA-associated vasculitis. The study was a randomized controlled trial involving 149 patients across multiple centers. Both groups also received tapering doses of prednisone. The primary goal was to evaluate if pulse cyclophosphamide was as effective as daily treatment, but with fewer side effects due to the lower cumulative dose. Outcomes such as remission rates, adverse events, and relapse rates were compared between the two groups.
ATT induced liver injury is very common with anti tubercular drugs as tuberculosis is one of the most common infection in india. Management of att liver injury is very important in medicine and is elaborated here.
Fexofenadine is sold under the brand name Allegra.
It is a selective peripheral H1 blocker. It is classified as a second-generation antihistamine because it is less able to pass the blood–brain barrier and causes lesser sedation, as compared to first-generation antihistamines.
It is on the World Health Organization's List of Essential Medicines. Fexofenadine has been manufactured in generic form since 2011.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
- Video recording of this lecture in English language: https://youtu.be/RvdYsTzgQq8
- Video recording of this lecture in Arabic language: https://youtu.be/ECILGWtgZko
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Milan J. Anadkat, MD, and Dale V. Reisner discuss generalized pustular psoriasis in this CME activity titled "Supporting Patient-Centered Care in Generalized Pustular Psoriasis: Communications Strategies to Improve Shared Decision-Making." For the full presentation, please visit us at www.peervoice.com/HUM870.
CLASSIFICATION OF H1 ANTIHISTAMINICS-
FIRST GENERATION ANTIHISTAMINICS-
1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE,PROMETHAZINE,HYDROXYZINE 2)MODERATELY SEDATIVE- PHENARIMINE,CYPROHEPTADINE, MECLIZINE,CINNARIZINE
3)MILD SEDATIVE-CHLORPHENIRAMINE,DEXCHLORPHENIRAMINE
TRIPROLIDINE,CLEMASTINE
SECOND GENERATION ANTIHISTAMINICS-FEXOFENADINE,
LORATADINE,DESLORATADINE,CETIRIZINE,LEVOCETIRIZINE,
AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE. Mechanism of action of 2nd generation antihistaminics-
These drugs competitively antagonize actions of
histamine at the H1 receptors.
Pharmacological actions-
Antagonism of histamine-The H1 antagonists effectively block histamine induced bronchoconstriction, contraction of intestinal and other smooth muscle and triple response especially wheal, flare and itch. Constriction of larger blood vessel by histamine is also antagonized.
2) Antiallergic actions-Many manifestations of immediate hypersensitivity (type I reactions)are suppressed. Urticaria, itching and angioedema are well controlled.3) CNS action-The older antihistamines produce variable degree of CNS depression.But in case of 2nd gen antihistaminics there is less CNS depressant property as these cross BBB to significantly lesser extent.
4) Anticholinergic action- many H1 blockers
in addition antagonize muscarinic actions of ACh. BUT IN 2ND gen histaminics there is Higher H1 selectivitiy : no anticholinergic side effects
Spontaneous Bacterial Peritonitis - Pathogenesis , Clinical Features & Manage...Jim Jacob Roy
In this presentation , SBP ( spontaneous bacterial peritonitis ) , which is a common complication in patients with cirrhosis and ascites is described in detail.
The reference for this presentation is Sleisenger and Fordtran's Gastrointestinal and Liver Disease Textbook ( 11th edition ).
Selective alpha1 blockers are Prazosin, Terazosin, Doxazosin, Tamsulosin and Silodosin majorly used to treat BPH, also hypertension, PTSD, Raynaud's phenomenon, CHF
Receptor Discordance in Breast Carcinoma During the Course of Life
Definition:
Receptor discordance refers to changes in the status of hormone receptors (estrogen receptor ERα, progesterone receptor PgR, and HER2) in breast cancer tumors over time or between primary and metastatic sites.
Causes:
Tumor Evolution:
Genetic and epigenetic changes during tumor progression can lead to alterations in receptor status.
Treatment Effects:
Therapies, especially endocrine and targeted therapies, can selectively pressure tumor cells, causing shifts in receptor expression.
Heterogeneity:
Inherent heterogeneity within the tumor can result in subpopulations of cells with different receptor statuses.
Impact on Treatment:
Therapeutic Resistance:
Loss of ERα or PgR can lead to resistance to endocrine therapies.
HER2 discordance affects the efficacy of HER2-targeted treatments.
Treatment Adjustment:
Regular reassessment of receptor status may be necessary to adjust treatment strategies appropriately.
Clinical Implications:
Prognosis:
Receptor discordance is often associated with a poorer prognosis.
Biopsies:
Obtaining biopsies from metastatic sites is crucial for accurate receptor status assessment and effective treatment planning.
Monitoring:
Continuous monitoring of receptor status throughout the disease course can guide personalized therapy adjustments.
Understanding and managing receptor discordance is essential for optimizing treatment outcomes and improving the prognosis for breast cancer patients.
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
GASTROINTESTINAL INFECTIONS AND GASTRITIS
Osvaldo Bernardo Muchanga
Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Lymphoma diffuse large cells.docx
1. DIFFUSE LARGE B-CELL NON-HODGKIN’S LYMPHOMA (DLBCL)
Aspect Summary
Prevalence
- Diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) is the most
common aggressive B-cell lymphoma, accounting for ∼
30% of all
lymphomas.
Age at Diagnosis - Median age at first diagnosis is approximately 70 years.
First-line Cure Rate
- Between 50% and 60% of all patients are cured with rituximab-
based chemoimmunotherapy in the first-line setting.
Treatment-Related Morbidity
and Mortality
- Treatment leads to substantial morbidity due to acute and long-
term toxicity.
- Treatment-related mortality ranges from 2% to 8%.
Relapse and Refractory Disease
- Relapsed or refractory disease typically occurs within the first 2
years after diagnosis.
Treatment Options for Relapsed
Disease
- More intensive treatment with high-dose chemotherapy, CD-19-
directed CAR-T-cell therapy, or experimental therapy in eligible
patients.
Term Definition
Single MYC
Rearrangement
A genetic alteration in which the MYC gene, which plays a role in cell
growth and division, undergoes rearrangement or translocation involving
its genetic material. In DLBCL, it often leads to overexpression of the MYC
protein and can be associated with aggressive disease behavior.
Double-Expressor DLBCL
A subtype of DLBCL characterized by the concurrent overexpression of both
MYC and BCL2 proteins. This phenotype is associated with inferior
outcomes following standard therapies and may require alternative
treatment strategies.
Double-Hit or Triple-Hit
DLBCL with MYC and BCL2 and/or BCL6 genomic rearrangements, referred
to as "double-hit" or "triple-hit" lymphomas. These are high-risk subtypes
associated with a worse prognosis following standard
chemoimmunotherapy, often requiring more intensive treatments such as
dose-intense regimens or stem cell transplantation.
2. Parameter General Index Age Adjusted Index
Age > 60 years 1 n.a.
PS (Performance Status) 1 1
Stage 3-4 1 1
LDH elevated 1 1
Extra nodal >1 site non considered 5
No. of Risk Factors IPI Group
0 - 1 1 = low
2 2 = low intermediate
3 3 = high intermediate
4 - 5 4 = high
Treatment Drugs Included Response
Rate
Progression-
Free Survival
Overall
Survival
First Line
R-CHOP Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine,
Prednisone
~70% ~3 years ~60% at 5
years
DA-EPOCH-R Rituximab, Etoposide, Prednisone,
Vincristine, Cyclophosphamide,
Doxorubicin
~80% ~3 years ~60% at 5
years
3. Polatuzumab
vedotin + R-CHP
Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine,
Prednisone, Polatuzumab vedotin
~85% Not yet
established
Not yet
established
Acalabrutinib +
R-CHOP or R-
DHAP
Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine,
Prednisone (or High-Dose
Cytarabine) + Acalabrutinib
Not yet
established
Not yet
established
Not yet
established
Tafasitamab +
Lenalidomide +
R-CHP
Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine,
Prednisone, Tafasitamab,
Lenalidomide
Not yet
established
Not yet
established
Not yet
established
Second Line
ICE Ifosfamide, Carboplatin,
Etoposide
~60% ~2 years ~25-30% at
5 years
R-ICE Rituximab, Ifosfamide,
Carboplatin, Etoposide
~70% ~2 years ~30-40% at
5 years
GEMOX Gemcitabine, Oxaliplatin ~50% ~1.5 years ~35-40% at
5 years
Third Line
4. DHAP or ESHAP Cytarabine, Cisplatin,
Dexamethasone (or Etoposide,
Methylprednisolone, Cisplatin)
~50% ~1 year ~25-30% at
5 years
R-DHAP or R-
ESHAP
Rituximab, Cytarabine, Cisplatin,
Dexamethasone (or Etoposide,
Methylprednisolone, Cisplatin)
~60% ~1.5 years ~30-40% at
5 years
GDP Gemcitabine, Dexamethasone,
Cisplatin
~50% ~1 year ~25-30% at
5 years
Stage of Disease Treatment
Limited stage (stage I or II) Combined modality therapy consisting of 3-4 cycles of R-
CHOP chemotherapy followed by involved-field radiation
therapy (IFRT)
Advanced stage (stage III or IV) R-CHOP chemotherapy for 6-8 cycles
Advanced stage (stage III or IV) with high
tumor burden or poor prognostic factors
R-CHOP chemotherapy followed by high-dose
chemotherapy and autologous stem cell transplant (ASCT)
Relapsed or refractory disease Salvage chemotherapy followed by high-dose
chemotherapy and autologous stem cell transplant
(ASCT), or CAR T-cell therapy
5. Second-line treatment for patients
ineligible for ASCT
Polatuzumab vedotin in combination with bendamustine
and rituximab (BRP)
Maintenance therapy Lenalidomide or rituximab for up to 2 years after initial
therapy
Pharmaceutical
Name
Commercial
Name
Manufacturer Dose and Route of Administration
Polatuzumab
vedotin
Polivy Genentech/Roche 1.8 mg/kg intravenous
Acalabrutinib Calquence AstraZeneca 100 mg twice daily oral
Tafasitamab Monjuvi MorphoSys/Incyte 12 mg/kg intravenous over
approximately 30 minutes on days 1, 8,
15, and 22 of each cycle in combination
with lenalidomide
Lisocabtagene
maraleucel
Breyanzi Bristol Myers
Squibb/Juno
Therapeutics
A single infusion of 0.6 to 6.0 × 10^8
CAR-positive viable T cells in 68 to 92
mL via intravenous infusion
Umbralisib Ukoniq TG Therapeutics 800 mg orally once daily
Drugs Indications Year of
Approval
FDA
Approval
EMA
Approval
Clinical Trials Results
6. Polatuzumab
vedotin
In combination
with
chemotherapy
2019 Yes Yes GO29365
(NCT02257567)
Improved median
OS vs R-CHOP
(12.4 vs 4.7
months)
Acalabrutinib In combination
with
chemotherapy or
alone
2020 Yes Yes ACE-LY-308
(NCT02953814)
Improved ORR
and PFS vs
placebo
Tafasitamab In combination
with lenalidomide
2020 Yes Yes L-MIND
(NCT02399085)
Improved ORR
and CR vs
lenalidomide
alone
Lisocabtagene
maraleucel
(Liso-cel)
Relapsed or
refractory DLBCL
2021 Yes Pending TRANSCEND
(NCT02631044)
ORR of 73% and
CR of 53%
Umbralisib In combination
with ublituximab
2021 Yes Pending UNITY-NHL
(NCT02793583)
Improved ORR
and CR vs
ublituximab alone
Zanubrutinib In combination
with rituximab
2021 Yes Pending SEQUOIA
(NCT03332017)
Improved PFS and
ORR vs R-CHOP
Drugs Advantages Disadvantages Adverse Events (percentage)
Polatuzumab
vedotin
Improved
progression-free
survival and overall
survival when added
to chemotherapy
compared to
chemotherapy alone
Increased risk of
infection, liver
damage, and nerve
damage; infusion
reactions (31% had
grade 3 or higher)
Infections (48%), neutropenia (46%),
anemia (32%), thrombocytopenia
(21%), peripheral neuropathy (16%)
8. survival when added
to ublituximab
compared to
ublituximab alone
bleeding and skin
cancers
infection (23%), pneumonia (22%),
headache (21%), rash (21%),
abdominal pain (20%), decreased
appetite (19%), vomiting (19%),
peripheral edema (19%),
thrombocytopenia
Polatuzumab vedotin: Polatuzumab vedotin was approved by the FDA in 2019 for the treatment of
relapsed or refractory DLBCL in combination with bendamustine and rituximab (BRP), following at
least two prior therapies. In the updated table, polatuzumab vedotin is listed as a second-line
treatment option for patients who are ineligible for ASCT.
Acalabrutinib: Acalabrutinib is a Bruton's tyrosine kinase (BTK) inhibitor that was approved by the FDA
in 2020 for the treatment of adult patients with relapsed or refractory DLBCL who have received at
least two prior lines of systemic therapy. However, it should be noted that acalabrutinib is currently
not listed in the NCCN guidelines as a standard treatment option for DLBCL.
Tafasitamab: Tafasitamab is a CD19-directed antibody that was approved by the FDA in 2020 for the
treatment of relapsed or refractory DLBCL in combination with lenalidomide. In the updated table,
tafasitamab is not listed as a standard treatment option, but could be considered in certain cases as
salvage therapy.
Lisocabtagene maraleucel: Lisocabtagene maraleucel (liso-cel) is a chimeric antigen receptor (CAR) T-
cell therapy that targets CD19. It was approved by the FDA in 2021 for the treatment of relapsed or
refractory DLBCL after at least two prior therapies. In the updated table, liso-cel is listed as a potential
option for patients with relapsed or refractory disease.
Umbralisib: Umbralisib is a phosphoinositide 3-kinase (PI3K) delta inhibitor that was granted
accelerated FDA approval in 2021 for the treatment of relapsed or refractory marginal zone lymphoma
and follicular lymphoma. It has not yet been approved for the treatment of DLBCL.
9.
10.
11.
12.
13. Table 1: Diagnosis, Staging, and Initial Work-up
Aspect Summary
Initial Work-up
- Includes complete physical examination, blood count, renal and liver
function, and more.
- Contrast-enhanced CT scan of neck, thorax, and abdomen is often
performed at first presentation.
- Bone-marrow biopsy with t(14;18) analysis is conducted in all patients to
exclude lymphoma infiltration.
14. Aspect Summary
Risk Stratification
- IPI (International Prognostic Index) used for risk assessment at initial
diagnosis.
- CNS-IPI for estimating individual prognosis and CNS involvement risk.
- Consider cerebral MRI and cerebrospinal fluid analysis for high CNS-IPI or
neurological symptoms.
- Additional risk factors discussed but not conclusive for CNS involvement.
Comorbidity
Assessment
- Echocardiography, electrocardiogram, brain natriuretic peptide for
anthracycline-based chemotherapy.
- HIV, hepatitis B and C serology checked before treatment.
Psychological Support - Psychological support offered to patients and families at initial diagnosis.
Table 2: Histological Assessment at First Diagnosis
Aspect Summary
Histological
Assessment
- Histological assessment is the cornerstone of first diagnosis.
- Standard immunohistochemistry panel used for B- and T-cell markers and
cell of origin analysis.
- MYC, BCL2, and BCL6 FISH analysis conducted as per WHO classification.
- Assessment of human herpesvirus-8 status in relevant pleural or peritoneal
effusion cases.
Table 3: First-line Treatment of Low-risk Patients
Aspect Summary
Low-risk Patients- Rituximab-based chemoimmunotherapy for patients with an IPI below 2.
- Equivalence of four vs. six cycles of R-CHOP chemotherapy in limited disease.
- Abbreviated treatment and interim PET for selected patients with low-risk and
limited-stage disease.
- Consider consolidation radiotherapy or prolonging R-CHOP for positive interim
PET cases.
15. Aspect Summary
- Repeated biopsy for patients with progressive disease based on CT and PET after
three cycles of R-CHOP.
Table 4: First-line Treatment of Higher-risk Patients
Aspect Summary
Higher-risk Patients - Polatuzumab vedotin preferred in patients with IPI >2.
- Use of anti-nausea medications and filgrastim to manage chemotherapy side
effects.
- Liposomal anthracyclines in patients with cardiovascular risk factors and
age >60 years.
- Clinical examination and CT/PET scans during treatment to assess response.
- Consider early PET scans for patients with signs of early progression.
Table 5: Survivorship and Follow-up After First-line Treatment
Aspect Summary
Survivorship and Follow-
up
- Psychological support and psychotropic drugs offered for anxiety.
- Symptomatic treatment for polyneuropathy, dose reductions, and
rehabilitation clinics recommended.
- Avoid regular CT scans in asymptomatic patients due to lack of efficacy.
- Recommended follow-up includes blood count, renal and liver function,
LDH, and clinical examination.
- Use chest X-ray and ultrasonography for selected cases.
Table 6: Relapsed or Refractory Disease
Aspect Summary
Relapsed or Refractory
Disease
- Conduct a new biopsy to confirm malignancy and the former diagnosis.
- CAR-T-cell therapy preferred in the second-line setting for eligible
patients.
16. Aspect Summary
- Alternative therapeutic antibodies, such as polatuzumab vedotin and
tafasitamab with lenalidomide, used.
- Epcoritamab and glofitamab considered for heavily pretreated patients.
- Individualized treatment decisions for patients not recruitable to clinical
trials.
Table: Evolving Treatment Approaches for Diffuse Large B-cell Lymphoma (DLBCL)
Aspect Summary
CAR T-Cell Therapy
- Three FDA-approved options for relapsed/refractory DLBCL patients who had
at least two prior lines of therapy.
- Recent approvals for second-line therapy (axicabtagene ciloleucel and
lisocabtagene maraleucel) based on ZUMA-7 and TRANSFORM studies.
TRANSFORM Study
- TRANSFORM study compared liso-cel to standard-of-care (high-dose
chemotherapy and autologous stem cell transplantation).
- Liso-cel group showed significantly improved median event-free survival,
progression-free survival, and complete response rate.
- Low rates of grade 3 cytokine release syndrome (1%) and neurologic events
(4%).
Glofitamab
- A promising CD20/CD3 bispecific monoclonal antibody for relapsed/refractory
DLBCL patients.
- Phase 2 trial results showed significant complete and objective response rates,
with low-grade cytokine release syndrome.
Bispecific
Antibodies
- Advantages include off-the-shelf access and favorable toxicity profiles.
- Longer follow-up needed to determine response durability beyond 1 year.
Future Directions
- Questions about sequencing with CAR T-cell therapy and combining bispecific
antibodies with other regimens.
- Ongoing studies of bispecific antibodies in combination with
chemoimmunotherapy and other treatments.
17. Table: Axi-Cel Therapy for Relapsed/Refractory Large B-cell Lymphoma
Aspect Summary
Response Rates
- In a multicenter phase 2 trial, 82% of patients with refractory
large B-cell lymphoma had an objective response, and 54% had a
complete response with axi-cel therapy.
Comparison to Existing
Therapies
- Axi-cel response rates compare favorably to SCHOLAR-1 study
results for existing therapies (objective response rate of 26% and
complete response rate of 7%).
Duration of Response
- Responses were ongoing in 42% of patients, including 40% with a
complete response, with the emergence of a plateau in response
duration at 6 months.
Monitoring for Improved
Response
- Consider monitoring patients without a complete response at the
first assessment for an opportunity for improvement, as
consolidation with allogeneic stem-cell transplantation has high
treatment-related mortality.
Overall Survival
- Median overall survival not reached; 18-month overall survival
rate of 52%. Ongoing durable remissions observed at 24 months.
Consistency Across Covariates
- Responses consistent across key covariates, including CD19 status
and T-cell phenotypes.
Need for Prospective Data
- Prospective data needed to understand the influence of disease
biology (e.g., double- and triple-hit lymphomas) on CAR T-cell
therapy outcomes.
Centralized Manufacturing and
Coordination
- Confirmed feasibility and reliability of centralized manufacturing
and coordination of leukapheresis procedures.
Feasibility in Medical Facilities
- Axi-cel safely administered even in centers with no prior CAR T-
cell therapy experience.
Management of Cytokine
Release Syndrome
- Effective implementation of algorithms for cytokine release
syndrome management; incidence decreased over time.
Safety Compared to Allogeneic
Stem-Cell Transplant
- Favorable 3% rate of death during treatment compared to
allogeneic stem-cell transplantation rates.
Correlation of CAR T-Cell Levels
with Response
- CAR T-cell levels during the first 28 days correlated with objective
response, supporting the potential for higher levels to augment
efficacy.
18. Aspect Summary
Biomarker Analysis
- Serum biomarker analysis confirmed associations with the
cytokine release syndrome and neurologic events, aiding in
understanding adverse events.
Use of Immunosuppressive
Agents
- Use of tocilizumab or glucocorticoids did not appear to affect
overall response.
Future Optimization and
Combinations
- Ongoing exploration of CAR construct and manufacturing
optimization and combination strategies with immunomodulatory
agents.
Table 1: Current First-Line Treatment of DLBCL
Treatment Patient Population Key Findings
R-CHOP
Elderly patients
(60-80 years)
Improved complete response rates (76% vs 63%) compared to
CHOP. Improved EFS and OS without increased toxicity. 10-year
PFS: 36.5% with R-CHOP vs 20% with CHOP alone. 10-year OS:
43.5% with R-CHOP vs 27.6% with CHOP alone. [16,17]
R-CHOP
Young patients (18-
60 years)
Increased complete response rates, improved EFS, and OS. 6-
year EFS: 74.3% with R-CHOP+rituximab vs 55.8% without. 6-
year OS: 90.1% with R-CHOP+rituximab vs 80.0% without.
[18,19]
R-CHOP
Elderly patients
(≥60 years)
No significant difference in outcomes between six and eight
cycles of R-CHOP. [20]
R-CHOP
Standard First-Line
Therapy
Six cycles of R-CHOP established as standard first-line therapy
for DLBCL.
Table 2: Beyond Standard R-CHOP Therapy
Treatment Patient Population Key Findings
R-ACVBP
Young patients (18-59
years)
Significantly improved EFS and OS but logistically
complex and with high risk of hematological
toxicities. Limited to patients with aa-IPI scores of
1. [21]
DA-EPOCH-R Not specified
No demonstrated significant benefit over R-CHOP.
[22]
High-dose
chemotherapy (HDC)
Not specified
No demonstrated significant benefit over R-CHOP.
[23,24,25]
19. Treatment Patient Population Key Findings
Novel agents with R-
CHOP
Not specified
None showed significant success despite promising
early signals of efficacy. [26-31]
Lenalidomide
Elderly patients
responding to R-CHOP
Maintenance therapy with lenalidomide prolonged
PFS but no OS benefit. Controversial due to
toxicities. [32]
Polatuzumab vedotin
(pola-R-CHP)
Intermediate to high-risk
DLBCL (IPI score ≥ 2)
Improved PFS over R-CHOP. No significant OS
difference. [37,38]
Polatuzumab vedotin
(pola-R-CHP)
Intermediate to high-risk
DLBCL (IPI score ≥ 2)
Less subsequent treatment required with pola-R-
CHP. [37,38]
Table 3: Low Risk Patients with Limited-Stage Disease
Treatment Patient Population Key Findings
R-CHOP
Limited stage (I or II) with aa-IPI of
0 and non-bulky disease (< 7.5 cm)
Highly favorable outcomes with 6-
year PFS approximating 90% and OS
at 95%. [18,19]
CHOP + Radiation Limited stage disease
Non-inferior to eight cycles of CHOP
alone but inadequate by modern
standards. [43,44]
Four cycles of R-CHOP + Two
additional rituximab doses
Young patients (18-60 years) with
limited stage and non-bulky
disease (< 7.5 cm), good ECOG
performance status (0-1), and
normal serum LDH levels
Non-inferior to standard six cycles
of R-CHOP. [46]
PET Response-Adapted
Approach
Limited stage (non-bulky < 10 cm)
and aa-IPI of 0
Four cycles of R-CHOP in case of
negative interim PET resulted in
excellent survival. [47]
PET Response-Adapted
Approach
Limited stage (aa-IPI scores of 0)
A negative interim PET allowed
patients to receive four cycles,
while a positive interim PET led to
six cycles. Non-inferiority
demonstrated. [48]
Table 1: Current First-Line Treatment of DLBCL
20. Treatment Category Treatment Regimen Patient Criteria Outcomes
Standard-Risk DLBCL
R-CHOP
chemoimmunotherapy
All standard-risk
DLBCL patients
6 cycles, 21-day cycle
Intermediate/High-
Risk
Pola-R-CHP
IPI score of 2–5, cost
not a limiting factor
6 cycles, 21-day cycle
Low Risk (Limited-
Stage)
Abbreviated R-CHOP
Limited stage (I or II)
with aa-IPI of 0, non-
bulky
4 cycles, 21-day cycle
Abbreviated R-CHOP (FLYER
Criteria)
Limited stage, non-
bulky, good ECOG,
normal LDH
4 cycles R-CHOP followed
by 2 cycles rituximab
PET-Guided Approach
For selected "low-
risk" DLBCL cases
3-4 cycles R-CHOP followed
by consideration of
consolidation radiation
therapy, guided by PET
imaging
Table 2: High-Risk Genetics in DLBCL
High-Risk Genetics Treatment Regimen Patient Criteria Notes
Single MYC
Rearrangement
R-CHOP
chemoimmunotherapy
All patients with single
MYC rearrangements
6 cycles, 21-day cycle
Double-Expressor
DLBCL
R-CHOP
chemoimmunotherapy
All patients with double-
expressor DLBCL
6 cycles, 21-day cycle
Double-Hit or Triple-Hit DA-EPOCH-R or R-CHOP
Patients with double-hit
or triple-hit genetics
6 cycles, 21-day cycle
for both DA-EPOCH-R
and R-CHOP
Consideration of
consolidation
therapies
Table 3: Special Considerations
Patient Group Treatment Regimen Patient Criteria Notes
Elderly and Frail
R-miniCHOP or other
regimens
Patients aged over 80
years or frail patients
Consideration of alternative
regimens
Disease Site-
Specific
Various
Based on primary site of
the disease
Tailored treatment approaches
for specific disease sites
21. Patient Group Treatment Regimen Patient Criteria Notes
DLBCL in HIV/AIDS
DA-EPOCH-R or
Abbreviated EPOCH-
RR
Patients with HIV-
associated DLBCL
Consideration of response-
adapted strategies
Table 4: Role of CNS Prophylaxis in DLBCL
CNS Prophylaxis
Strategy
Patient Criteria Preferred Method Notes
HD-MTX
High CNS-IPI scores, high-
risk sites
Over IT prophylaxis
Intercalated or at the end of
induction
Intrathecal (IT) MTX
Variable based on
guidelines
Less preferred
May not significantly reduce
CNS relapse
Table 1: Treatment Options for Relapsed or Refractory DLBCL
Patient Eligibility Treatment Regimen Notes
Transplant Eligible R-ICE, R-DHAP, R-GDP, Pola-R-ICE
High-dose chemotherapy followed by
ASCT is a curative option
Transplant
Ineligible
R-GDP, R-GEMOX, Pola-BR, Pola-R-ICE
Options for patients ineligible for ASCT or
CAR-T therapy
CAR-T Therapy
Eligible
CD19-directed CAR-T therapies
Axicabtagene ciloleucel, tisagenlecleucel,
lisocabtagene maraleucel for eligible
patients
CAR-T Therapy
Ineligible
Pola-BR, Tafasitamab + Lenalidomide,
Loncastuximab tesirine, Selinexor
Options for patients not eligible for ASCT
or CAR-T therapy
Table 2: Use of Next-Generation Sequencing in DLBCL
Molecular Classification
System
Clinical Implications Current Clinical Practice
Molecular Classification
Systems
Identification of unique
genomic subtypes
Subtyping DLBCL based on molecular
classification systems is not yet a standard
practice in current clinical treatment
decisions.
C1 to C5, BN2, A53, EZB,
ST2, MCD, N1
Genetic clusters with
distinct signatures
These classifications are based on whole
exome and deep targeted sequencing and
may guide future clinical trials.
22. Molecular Classification
System
Clinical Implications Current Clinical Practice
LymphGen Probabilistic
Classifier
Assign patients to genetic
subtypes
Currently, routine genomic profiling's value in
frontline or relapsed treatment selection is
unclear.
Heterogeneity of DLBCL
Potential rational
explanation for targeted
therapy failures
Challenges, costs, and implications on
treatment selection need further study.