The Top 5 Blood Cancer Advancements in 2025

The past year in hematologic oncology was defined by a mix of breakthrough clinical success and rigorous regulatory scrutiny, marking a continuous push to overcome treatment resistance and optimize patient outcomes. While new agents and regimens delivered practice-changing efficacy in diseases ranging from myeloma and leukemia to essential thrombocythemia (ET), the field also faced complex discussions surrounding trial generalizability and toxicity management.

Key advancements include the success of ropeginterferon alfa-2b in ET, and the emergence of Bruton tyrosine kinase (BTK) degraders as a novel strategy to overcome resistance in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Conversely, the FDA's Oncologic Drug Advisory Committee (ODAC) highlighted critical concerns about trial applicability and risk-benefit profiles, specifically for glofitamab in diffuse large B-cell lymphoma (DLBCL) due to regional enrollment bias, and for belantamab mafodotin in multiple myeloma due to unresolved ocular toxicity at the proposed dosing. Finally, studies refined prognostic factors in rare, aggressive diseases like plasma cell leukemia (PCL), reaffirming the indispensable role of transplantation.

Here are the top 5 articles detailing the advancements in hematologic oncology from 2025.

Resistance Spurs Evaluation of Early-Phase BTK Degraders

BTK inhibitors have revolutionized treatment for hematologic malignancies, butacquired BTK mutations often lead to widespread resistance. This challenge is driving the development of a new class of drugs: BTK degraders.

Early-phase 1 data presented highlighted the promise of these novel agents. Drugs like BGB-16673 demonstrated high overall response rates (ORR), including 77.6% in relapsed/refractory (R/R) CLL /SLL, and activity in patients previously treated with BTK inhibitors.

BTK degraders work by leveraging the cell’s machinery to physically destroy the BTK protein, a mechanism that can potentially overcome resistance mutations that thwart traditional inhibitors. They show manageable safety profiles, signaling a potential new standard for patients who have progressed on current BTK therapies.

ODAC Votes STARGLO Trial Not Applicable to US Patients With DLBCL

The ODAC voted 8-to-1 that the findings from the phase 3 STARGLO trial for glofitamab-gxbm in R/RDLBCL are not reliably applicable to the US patient population.

While the global trial met its primary endpoint, showing that glofitamab plus GemOx significantly improved overall survival (OS; 25.5 months vs 12.9 months) and progression-free survival (PFS) compared to rituximab plus GemOx, the FDA raised concerns about the trial's regional imbalance. Only 9% of patients were enrolled in the US, while 48% came from Asian regions, where efficacy appeared substantially higher. Due to insufficient US patient data and confounding factors, ODAC concluded the trial lacked generalizability for US clinical practice.

FDA ODAC Votes BelantamabMafodotin Risks Outweigh Benefits in Myeloma

The FDA's ODACvoted that the benefit-risk profile of belantamabmafodotin (Blenrep) combination regimens for early R/R multiple myeloma was unfavorable. Despite strong efficacy from the DREAMM-7 and DREAMM-8 trials, the committee cited major concerns regarding the drug's severe and recurrent ocular toxicity (keratopathy). ODAC concluded that the proposed dosages were not adequately optimized, leading to very high rates of required dose modifications (over 75% of patients). The majority of the committee determined that the high, unmitigated toxicity risk at the current dosing regimen outweighed the clinical benefit, leading to the unfavorable vote. However, the FDA went on to approve the agent in October.

Clinical Factors and Transplantation Are Associated With PCL Prognosis

A retrospective study of PCL, encompassing both primary (pPCL) and secondary (sPCL) subtypes, revealed significant survival disparities. Patients with the more aggressive sPCL had a dramatically shorter median OS of 3.2 months, compared to 36.6 months for pPCL. Crucially, the analysis confirmed that hematopoietic stem cell transplantation was strongly associated with better outcomes, prolonging median OS to 48.7 months for the transplanted cohort across both subtypes. There was no difference in benefit between autologous and allogeneic transplantation. The findings underscore the critical need for new therapeutic strategies, especially for sPCL, and highlight transplantation as a key prognostic factor.

Ropeginterferon Alfa-2b Succeeds in Phase 3 Essential Thrombocythemia Trial

The SURPASS-ET phase 3 trial demonstrated that ropeginterferon alfa-2b (Besremi) is superior to anagrelide for treating patients with ET.The study met its primary endpoint, with 42.9% of ropeginterferon alfa-2b patients achieving a durable clinical response at 9 and 12 monthscompared with only 6% for anagrelide. Furthermore, ropeginterferon alfa-2b showed a greater reduction in the underlying disease pathology by significantly decreasing the JAK2 V617F allele burden. The drug, already approved for polycythemia vera, had a manageable safety profile. These positive results will be submitted to the FDA to pursue label expansion for ET.