Preface – EHA 2024
© private – Sigrid S. Skånland, PhD, Oslo University Hospital, Oslo, Norway
Dear Colleagues,
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). In the treatment-naïve CLL section of this report, you will discover results for innovative therapies such as zanubrutinib combined with venetoclax, the triplet regimen of pirtobrutinib, venetoclax, and obinutuzumab, and the comparative efficacy of ibrutinib and venetoclax against standard treatments. Data from the CAPTIVATE study shed light on retreatment outcomes in high-risk patients. In the relapsed/refractory setting, studies have explored promising strategies such as prolonged induction with ibrutinib and venetoclax, pirtobrutinib monotherapy, and obinutuzumab in addition to ibrutinib and venetoclax. Analyses have investigated the relative efficacy and safety of BTK inhibitors, with real-world data confirming these observations.
The second chapter deals with unmet needs in mantle cell lymphoma (MCL), where the ECHO study investigating acalabrutinib plus chemoimmunotherapy as well as the phase II trial evaluating the BOVen triplet regimen are pointing towards alternative treatment approaches in older MCL patients. In the relapsed/refractory setting, high response rates and durable remissions have been reported for glofitamab, and real-world data have shown favorable results for zanubrutinib compared to other BTK inhibitors with respect to survival outcomes and treatment adherence.
The emerging class of BTK degraders that includes agents such as NX-5948 and BGB-16673 addresses resistance patterns in B-cell malignancies that limit the utility of BTK and BCL2 inhibitors. Phase I/II data have demonstrated promising efficacy even in hard-to-treat populations with relapsed/refractory disease.
The BCL2 inhibitor sonrotoclax has shown impressive results across CLL, MCL, Waldenström macroglobulinemia, multiple myeloma and AML. Studies have revealed high uMRD rates and a favorable safety profile, while the clinical development is ongoing.
Bispecific antibodies like odronextamab and mosunetuzumab have proven effective in relapsed/refractory follicular lymphoma across patients with and without poor-prognosis factors such as progression of disease within 24 months of initiation of first-line treatment. For epcoritamab, cycle 1 optimization has been successfully explored regarding reductions in typical adverse events.
Last but not least, the matching-adjusted indirect comparison (MAIC) technique is highlighted as it enables the assessment of new treatments versus alternatives where direct comparisons through randomized controlled trials are not available, aiding decision-making in oncology and hematology by addressing uncertainties related to disease severity and treatment costs.
We hope that you enjoy reading about the groundbreaking findings from EHA 2024 in the field of hematology. Together, let us continue advancing research for the benefit of our patients.
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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].
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.
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].
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].
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].
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].
