Richter transformation-is there light at the end of this tunnel?
This article reviews recent therapeutic developments, focusing on inhibitors of BTK, BCL2, the PD1-PDL1 axis, and T-cell-activating/engaging therapies. Herein, I discuss the importance of randomized clinical trials in a disease where small single-arm studies dominate; industry engagement, including the role of registrational studies; and the need to integrate prospectively planned correlative biological studies embedded within future clinical trials to help discover which patient benefits most from each class or combination of novel targets.PMID:38066897 | PMC:PMC10727096 | DOI:10.1182/hematology.2023000442 (Source: Hemato...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Toby A Eyre Source Type: research
Managing side effects: guidance for use of immunotherapies in multiple myeloma
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):348-356. doi: 10.1182/hematology.2023000435.ABSTRACTChimeric antigen receptor T-cell therapy and bispecific T-cell recruiting antibodies have transformed the treatment landscape for relapsed/refractory multiple myeloma, with B-cell maturation antigen being the most common target and other targets in clinical development. However, these therapies are associated with unique and severe toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), delayed neurotoxicity, cytopenias, and infection. In addition, imm...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Emily C Liang Surbhi Sidana Source Type: research
How to avoid early mortality in acute promyelocytic leukemia
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):248-253. doi: 10.1182/hematology.2023000477.ABSTRACTAcute promyelocytic leukemia (APL), a phenotypically and genotypically unique subtype of acute myeloid leukemia, has seen unprecedented advances in its management since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide. However, the phenomenal pharmacologic conversion of this once highly fatal disease to one with a long-term survival exceeding 90% among patients who survive induction remains impaired by the significant incidence of early death (ED) reaching 30% in some real-world studies. The...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Oluwatobi Odetola Martin S Tallman Source Type: research
Minimal intensity conditioning strategies for bone marrow failure: is it time for "preventative" transplants?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):135-140. doi: 10.1182/hematology.2023000470.ABSTRACTHematopoietic cell transplantation (HCT) can cure blood dyscrasias and reduce the risk of hematologic cancers in patients with inherited bone marrow failure syndromes (IBMFS). However, because of its high mortality rate, HCT is generally reserved until patients with IBMFS manifest life-threatening cytopenias or myeloid malignancy, at which point outcomes are poor. Screening tests that accurately predict transformation and enable timely intervention are lacking. These unknowns and risks limit the use of HCT in pati...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Suneet Agarwal Source Type: research
Stem cell transplantation for ALL: you've always got a donor, why not always use it?
This article reviews critical current evidence and debates the potential of HSCT as a more universal treatment for ALL, reevaluating traditional treatment stratification in light of the constant availability of stem cell donors.PMID:38066901 | PMC:PMC10726989 | DOI:10.1182/hematology.2023000423 (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: David Shyr Kara L Davis Alice Bertaina Source Type: research
Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):77-83. doi: 10.1182/hematology.2023000422.ABSTRACTThe tremendous successes of CD19-directed CAR T cells in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) has led to the more widespread use of this important treatment modality. With an ability to induce remission and potentially lead to long-term survival in patients with multiply relapsed/chemotherapy refractory disease, more children are now receiving this therapy with the hope of inducing a long-term durable remission (with or without consolidative hematopoietic cell transplantation). ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Rebecca Epperly Nirali N Shah Source Type: research
Should older patients with low weight and CKD receive full-dose DOACs for treatment of acute proximal DVT?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):614-616. doi: 10.1182/hematology.2023000515.NO ABSTRACTPMID:38066903 | PMC:PMC10727011 | DOI:10.1182/hematology.2023000515 (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Nicolas Gallastegui Camila Masias Source Type: research
How to diagnose and manage antiphospholipid syndrome
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):606-613. doi: 10.1182/hematology.2023000493.ABSTRACTAntiphospholipid antibodies (aPL) are autoimmune antibodies directed toward phospholipids or phospholipid-protein complexes, particularly those containing β2-glycoprotein I (β2GPI). Persistently positive aPL accompanied by arterial or venous thrombosis, or recurrent pregnancy loss, constitutes the antiphospholipid syndrome (APS). Several types of aPL with different specificities have been defined and may be detected in the clinical lab, including lupus anticoagulants (detected using clotting assays) and anticard...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Anne Hubben Keith R McCrae Source Type: research
Using disease-modifying therapies in sickle cell disease
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):519-531. doi: 10.1182/hematology.2023000485.ABSTRACTAs curative therapy using allogeneic hematopoietic stem cell transplantation as well as gene therapy and gene editing remains inaccessible to most patients with sickle cell disease, the availability of drug therapies that are safe, efficacious, and affordable is highly desirable. Increasing progress is being made in developing drug therapies based on our understanding of disease pathophysiology. Four drugs, hydroxyurea, L-glutamine, crizanlizumab, and voxelotor, are currently approved by the US Food and Drug Admin...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Parul Rai Kenneth I Ataga Source Type: research
The optimal management of relapsed and refractory Hodgkin lymphoma: post-brentuximab and checkpoint inhibitor failure
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):510-518. doi: 10.1182/hematology.2023000450.ABSTRACTThe treatment landscape of classical Hodgkin lymphoma has changed dramatically over the past decade. Relapsed and refractory mainstay therapeutics such as brentuximab vedotin (BV) and checkpoint inhibitors (CPIs) are being moved to earlier lines of therapy. However, the treatment of patients who progress after BV and CPI remains a challenge. Allogeneic stem cell transplantation still plays an important role in this patient population as the only current treatment approach with curative potential. Unfortunately, no...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Natalie S Grover Christopher Dittus Astha Thakkar Anne W Beaven Source Type: research
Selection of bispecific antibody therapies or CAR-T cell therapy in relapsed lymphomas
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):370-381. doi: 10.1182/hematology.2023000438.ABSTRACTPatients with relapsed and refractory (R/R) aggressive B-cell non-Hodgkin lymphomas have historically poor survival outcomes, with chimeric antigen receptor T-cell (CAR-T) therapy now presenting a curative option for a subset of those patients. However, with the approval of several novel bispecific monoclonal antibody (BsAb) therapies with considerable activity in R/R aggressive large B-cell lymphomas (LBCL), patients and oncologists will be faced with decisions regarding how to sequence CAR-T and BsAb therapies b...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Ajay Major Manali Kamdar Source Type: research
Management of aggressive lymphoma after CAR T-cell therapy failure
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):364-369. doi: 10.1182/hematology.2023000437.ABSTRACTSeveral recent advances have affected the treatment landscape of diffuse large B-cell lymphoma. Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of chemorefractory disease. Two randomized studies in early relapse disease have expanded the label to provide access to CAR T-cell therapy as early as second line for some patients. Despite the durable remissions that have been achieved, many patients will experience relapse. There is a growing population of patients previously treated with C...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Loretta J Nastoupil Swetha Kambhampati Source Type: research
Acute leukemias and complicated lymphomas: pearls to optimize management when patients stay local
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):311-317. doi: 10.1182/hematology.2023000430.ABSTRACTHematologic malignancies often present acutely with a constellation of infectious complications, pancytopenia, tumor lysis, and renal dysfunction. Acute leukemias and aggressive lymphomas often require hospitalization for rapid diagnostic evaluation, urgent management of complicating presentations, and timely management of intensive systemic therapies. There is an emerging paradigm whereby complex cancer care can be safely and effectively provided in the community, where the majority of cancer is treated. A substa...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Dipti Patel-Donnelly Mitul Gandhi Source Type: research
How to manage splanchnic vein thrombosis in patients with liver disease
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):281-288. doi: 10.1182/hematology.2023000481.ABSTRACTLiver cirrhosis and splanchnic vein thrombosis (SVT) are strictly correlated. Portal vein thrombosis, the most common location of SVT, is frequently diagnosed in liver cirrhosis (pooled incidence 4.6 per 100 patient-years), and liver cirrhosis is a common risk factor for SVT (reported in 24%-28% of SVT patients). In cirrhosis-associated SVT, anticoagulant treatment reduces mortality rates, thrombosis extension, and major bleeding, and increases the rates of recanalization, compared to no treatment. Achieving vesse...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Nicoletta Riva Walter Ageno Source Type: research
Pyruvate kinase activators: targeting red cell metabolism in thalassemia
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):114-120. doi: 10.1182/hematology.2023000468.ABSTRACTThalassemia is an inherited red blood cell disorder whereby the qualitative and/or quantitative imbalance in α- to β-globin ratio results in hemolysis and ineffective erythropoiesis. Oxidative stress, from the precipitated excess globin and free iron, is a major factor that drives hemolysis and ineffective erythropoiesis. Pyruvate kinase activity and adenosine triphosphate availability are reduced due to the overwhelmed cellular antioxidant system from the excessive oxidative stress. Mitapivat, a pyruvate kinase...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Kevin H M Kuo Source Type: research
