In today’s information overload era, how can one stay updated on the latest advancements in the field? Here, we curate the most recent literature each month, focusing on hot topics and offering a comprehensive analysis of the latest developments in hematologic diseases. Join us as we track the latest trends, gain insights into scientific research, and explore the limitless possibilities in the world of hematology. Stay tuned—don’t miss our monthly updates!01 Fixed-Duration Pirtobrutinib plus Venetoclax with or without Rituximab in Relapsed/Refractory CLL: Phase 1b BRUIN Trial
Journal: Blood
DOI: 10.1182/blood.2024024510
Impact Factor: 21
Authors: Lindsey Elizabeth Roeker et al.
This study is a multicenter, open-label Phase 1b clinical trial aimed at assessing the safety and efficacy of Pirtobrutinib combined with Venetoclax, with or without Rituximab, in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). The study enrolled 25 eligible patients, divided into the PV group (Pirtobrutinib plus Venetoclax) and the PVR group (Pirtobrutinib plus Venetoclax plus Rituximab). All patients were BCL-2i treatment-naive, but previous treatments with anti-CD20 antibodies and/or BTK inhibitors were allowed.
The results indicated no dose-limiting toxicities in either group, and the safety profile was favorable, with common adverse events including neutropenia and anemia. Among the ≥ Grade 3 adverse events, the PV group mainly experienced neutropenia, hypertension, and severe infections, while the PVR group encountered neutropenia, hypertension, bleeding, and severe infections. Regarding efficacy, the overall response rate (ORR) was 93.3% in the PV group and 100% in the PVR group, with complete response (CR) rates of 46.7% and 30%, respectively. The median progression-free survival (PFS) and overall survival (OS) were not reached in either group, with the 24-month PFS and OS rates estimated at 79.5% and 87.5%, respectively. Additionally, after 12 cycles of treatment, 85.7% of patients in the PV group and 90.0% in the PVR group achieved undetectable minimal residual disease (uMRD).
Pharmacokinetic analysis revealed similar pharmacokinetics for Pirtobrutinib and Venetoclax across both treatment regimens, with the addition of Rituximab not affecting the pharmacokinetics of either drug. The study concluded that fixed-duration PV or PVR regimens demonstrate good tolerability and promising efficacy in patients with R/R CLL, including those who have previously undergone covalent BTKi therapy, with no significant drug-drug interactions observed.
02 Asciminib Monotherapy in Patients with Chronic-Phase Chronic Myeloid Leukemia with the T315I Mutation After ≥1 Prior Tyrosine Kinase Inhibitor: 2-Year Follow-Up Results
Journal: Leukemia
DOI: 10.1038/s41375-024-02278-8
Impact Factor: 12.8
Authors: Jorge E Cortes et al.
Asciminib, a novel STAMP inhibitor, offers a new treatment option for chronic myeloid leukemia (CML) patients harboring the T315I mutation. In this first-in-human, dose-escalation Phase 1 study, 48 patients received Asciminib monotherapy, showing significant efficacy across various molecular response levels. Specifically, an early molecular response (EMR) was achieved in 62.2% of patients, while major molecular response (MMR) and deep molecular response (DMR/MR4) were attained in 48.9% and 28.9% of patients, respectively. Additionally, 24.4% of patients achieved the more stringent MR4.5 molecular response.
In terms of safety, all patients reported adverse events (AEs), with 60.4% experiencing Grade 3 or higher AEs. However, no safety signals were observed in the 150 mg BID and 160 mg BID dose groups, supporting further exploration of the 200 mg BID dose group. The main non-hematologic AEs included elevated pancreatic enzyme levels, fatigue, nausea, diarrhea, and vomiting, while hematologic AEs comprised thrombocytopenia, neutropenia, and anemia. AEs led to dose adjustments or interruptions in 39.6% of patients, with 5 patients discontinuing the study due to AEs.
Based on the combined efficacy and safety data, Asciminib monotherapy shows promising efficacy and acceptable safety in CML-CP patients with the T315I mutation, particularly in the approximately 50% of patients who had previously received Ponatinib therapy. These results support Asciminib as a viable treatment option for this patient population, bringing new hope to the field of CML therapy.
03 Chimeric Antigen Receptor T-Cell Infusion for Large B-Cell Lymphoma in Complete Remission: A Center for International Blood and Marrow Transplant Research Analysis
Journal: Leukemia
DOI: https://doi.org/10.1038/s41375-024-02242-6
Impact Factor: 12.8
Authors: Trent P. Wang et al.
This retrospective study evaluates the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with large B-cell lymphoma (LBCL) who were in complete remission (CR) before treatment. The study included 134 adult LBCL patients treated between 2018 and 2021, who had achieved imaging and/or metabolic CR prior to CAR-T therapy.
Baseline characteristics showed a median patient age of 63.9 years, with most patients having undergone multiple prior treatments, including autologous or allogeneic hematopoietic stem cell transplantation, and bridging therapy. In terms of efficacy, the study observed high rates of neutrophil and platelet recovery, with a 2-year non-relapse mortality (NRM) of 9.2%, a cumulative incidence of disease relapse or progression of 47.3%, a 2-year progression-free survival (PFS) rate of 43.5%, and an overall survival (OS) rate of 63.8%.
Regarding safety, the incidence of cytokine release syndrome (CRS) was 59.7%, with only 2.2% experiencing Grade ≥3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 23.8% of patients, with a Grade ≥3 incidence of 8.2%. The primary causes of death were disease relapse or progression, followed by infections, including COVID-19.
Univariate analysis indicated that patients who had received five or more lines of therapy before CAR-T had poorer PFS. Overall, the study concluded that patients treated with CAR-T while in CR showed 2-year PFS and OS rates similar to historical data, with low incidences of severe CRS and ICANS, providing a potential treatment option for LBCL patients.
