EHA 2024 – Consuelo Bertossi
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.
Here is the full EHA 2024 report.
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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].
