EHA 2024
Lecture Board: Othman Al-Sawaf, MD; Tycel Philipps, MD; John Seymour, MD; Constantine Tam, MD; Umberto Vitolo, MD; Talha Munir, MD
Medical Writer: Judith Moser, MD
Publishing Editor: Anna Fenzl, PhD
Preface – EHA 2024
At the European Hematology Association (EHA) congress held in Madrid, Spain, and virtually from 13th–16th June 2024, world-leading experts from 150 countries presented cutting-edge research and clinical trials. This year, we witnessed significant advancements in the treatment of chronic lymphocytic leukemia (CLL).
Reducing risks further in chronic lymphocytic leukemia
The second-generation BTK inhibitor zanubrutinib is being tested in the phase III SEQUOIA trial in the setting of untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with and without del(17p). Zanubrutinib monotherapy has shown high tolerability and efficacy in arm C of the study that included patients with del(17p) [1].
Meeting unmet needs in mantle cell lymphoma
In older or unfit patients with mantle cell lymphoma (MCL), bendamustine plus rituximab (BR) is the most common first-line therapy, while intensive regimens are usually unsuitable in this population even though they provide durable responses [1, 2]. The addition of the first-in-class BTK inhibitor ibrutinib to first-line BR has been shown to prolong progression-free survival (PFS) in the SHINE trial [3].
BTK degraders: emerging activity in various B-cell malignancies
The new class of BTK degraders is being developed in response to emerging patterns of resistance that limit the utility of BTK and BCL2 inhibitors. On one hand, BTK mutations decrease the efficacy of both covalent and non-covalent BTK inhibitors; on the other hand, some mutations lead to “kinase dead” or “kinase bypassing” BTK mutants with intact B-cell receptor signaling through a scaffolding function of BTK [1, 2].
Innovative BCL2 inhibition: indications fanning out across B-cell malignancies
The combination of the first-generation BCL2 inhibitor venetoclax and the first-in-class BTK inhibitor ibrutinib has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL) [1], although tolerability of this regimen is limited. Next-generation agents can be expected to provide optimized toxicity profiles. The second-generation BCL2 inhibitor sonrotoclax inhibits BCL2 in a more selective and pharmacologically potent manner than venetoclax, with a shorter half-life preventing drug accumulation that might contribute to toxicity [2].
Follicular lymphoma: news on bispecific antibody treatment
In the setting of relapsed/refractory follicular lymphoma (FL), progression-free survival (PFS) deteriorates with successive relapses, which implies a high unmet need for therapies that can improve disease control and extend survival after relapse [1]. The Fc-silenced CD20 x CD3 bispecific antibody odronextamab is being investigated in patients with relapsed/refractory B-cell malignancies in the multicohort, multicenter, phase II ELM-2 study.
Relative efficacy of several treatment options in marginal zone lymphoma
Chemoimmunotherapy (CIT), immunotherapy and chemotherapy regimens are commonly used for the treatment of patients with marginal zone lymphoma. Moreover, the BTK inhibitor zanubrutinib has shown activity in the relapsed/refractory setting based on the phase II, single-arm MAGNOLIA and BGB-3111-AU-003 trials [1, 2]. Walewska et al. conducted a matching-adjusted indirect comparison (MAIC) to estimate the comparative efficacy of these treatment strategies in relapsed/refractory marginal zone lymphoma [3].
Economic analysis of zanubrutinib vs. acalabrutinib in B-cell malignancies
A recent meta-analysis by Hwang et al. provided a comprehensive comparison of adverse event (AE) profiles of zanubrutinib with acalabrutinib in patients with B-cell malignancies. Specific AEs seen more commonly with acalabrutinib than zanubrutinib included infections, atrial fibrillation, diarrhea, nausea/vomiting, headaches, cough, fatigue and pyrexia. On the other hand, hematuria, neutropenia, and hypertension were observed more frequently with zanubrutinib than with acalabrutinib [1].
EXPERT VIDEOS
All video interviews from EHA 2024
Chan Cheah discusses key aspects of a disease-centered treatment approach for relapsed/refractory CLL, explains how B-cell degraders, compared to BTK inhibitors, can improve management of B cell malignancies, and highlights notable results for the BTK degrader BGB-16673 in relapsed or refractory indolent non-Hodgkin lymphoma.
Umberto Vitolo discusses emerging T-cell–engaging agents for B-cell lymphomas and their potential impact. He highlights the effectiveness of bispecific antibody therapy in later-line follicular lymphoma and shares insights from the EPCORE NHL-1 study, highlighting key safety and tolerability precautions for patients receiving the bispecific antibody epcoritamab.
Consuelo Bertossi explains how TP53 mutations affect the prognosis of CLL patients and their impact on treatment decisions. She also discusses the significance of co-occurring genetic alterations and highlights the influence of TP53 mutations on the efficacy of different treatment approaches in CLL, ahead of her presentation at this year’s EHA congress.
Nitin Jain elucidates the promising outcomes of the time-limited triplet therapy with pirtobrutinib, venetoclax, and obinutuzumab in first-line CLL treatment and addresses future challenges in clinical implementation. He shares recent advances in the development of more potent BTK inhibitors and depicts his personal highlights from this year’s EHA congress.
Clemens Wendtner provides insights on treatment selection in CLL, emphasizing key principles for first-line therapy and summarizes the recent GAIA/CLL13 data comparing venetoclax combinations with chemoimmunotherapy in fit untreated patients. Additionally, he discusses factors guiding treatment choices in relapsed/refractory CLL and highlights the benefits of BTK inhibitors in indolent lymphomas.
Talha Munir overviews the performance of next-generation BTK inhibitors like zanubrutinib in treating CLL, highlighting their efficacy and safety compared to older BTK inhibitors while further explaining the concept of matching-adjusted indirect comparison and its importance in future research. Lastly, he discusses how next-generation BTK inhibitors impact quality of life and their economic implications in B-cell malignancies.