The past year in hematologic oncology was marked by notable clinical advances alongside heightened regulatory scrutiny, as investigators pushed to overcome treatment resistance and optimize tolerability while regulators questioned trial generalizability and safety.
New BTK degraders emerged as a promising strategy to address resistance to Bruton tyrosine kinase (BTK) inhibitors. Early-phase data showed strong activity in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL), including an overall response rate of 77.6% reported for BGB-16673. These agents induce proteasomal destruction of the BTK protein, a mechanism that can bypass resistance mutations limiting the efficacy of traditional inhibitors, and they have shown manageable safety profiles in early studies.
The FDA’s Oncologic Drugs Advisory Committee (ODAC) raised concerns about the applicability of the phase 3 STARGLO trial of glofitamab in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Although the trial met its primary endpoint—glofitamab plus GemOx improved overall survival (25.5 vs 12.9 months) and progression-free survival versus rituximab plus GemOx—ODAC voted 8–1 that the results are not reliably generalizable to U.S. patients because only 9% of participants were enrolled in the United States while 48% were enrolled in Asian regions where efficacy appeared higher.
ODAC also found the benefit-risk profile of belantamab mafodotin in early relapsed/refractory multiple myeloma unfavorable due to severe and recurrent ocular toxicity (keratopathy). Despite efficacy signals in the DREAMM-7 and DREAMM-8 trials, the committee noted that proposed dosing led to high rates of dose modifications—over 75% of patients—and that ocular risks were insufficiently mitigated. The ODAC vote was unfavorable, though the FDA subsequently approved the agent in October.
A retrospective analysis of plasma cell leukemia (PCL) highlighted stark prognostic differences between subtypes and reinforced the importance of transplantation. Median overall survival was 36.6 months for primary PCL and 3.2 months for secondary PCL. Hematopoietic stem cell transplantation was associated with substantially improved outcomes, extending median overall survival to 48.7 months across both subtypes, with no clear difference in benefit between autologous and allogeneic approaches.
The SURPASS-ET phase 3 trial showed that ropeginterferon alfa-2b (Besremi) was superior to anagrelide in essential thrombocythemia. The study met its primary endpoint: 42.9% of patients receiving ropeginterferon achieved a durable clinical response at both 9 and 12 months versus 6% with anagrelide. Ropeginterferon also produced a greater reduction in JAK2 V617F allele burden and demonstrated a manageable safety profile. Plans are underway to submit these data to the FDA seeking label expansion for essential thrombocythemia.
Collectively, these findings illustrate both therapeutic progress—new mechanisms to overcome drug resistance and effective disease-modifying options—and the continued need for careful assessment of trial design and toxicity management to ensure treatments deliver meaningful benefit for broader patient populations.
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