Highlights from the 2025 ASH meeting: what’s new in lymphoma?

Abstract

Key lymphoma-focused themes at the annual meeting of the American Society of Hematology held in December 2025 (ASH2025) in Orlando, Florida, centered on pioneering concepts for vulnerable patient populations, including T‑cell-directed therapies, reduced chemotherapy, and the rising use of targeted therapeutics. The 5‑year follow-up of the pivotal POLARIX trial comparing R‑CHOP vs. polatuzumab(Pola)-R-CHP as first-line treatment (1L) in a higher-risk (International Prognostic Index ≥ 2) diffuse large B‑cell lymphoma (DLBCL) population confirmed superior progression-free survival (PFS) without statistically significant differences in overall survival (OS) in favor of Pola-R-CHP. Analyses of defined molecular subtypes highlighted a significant PFS benefit with the anti-CD79 antibody–drug conjugate (ADC) in the MCD subgroup. Bispecific antibodies (BsAb)—with glofitamab in combination with chemotherapy already approved in second-line treatment (2L) and glofitamab and epcoritamab monotherapy in 3L—are now being tested in 1L combinations, among them odronextamab plus CHOP (Olympia-3), epcoritamab plus Pola-R-CHP (EPCORE NHL-5), or glofitamab in combination with R‑CHOP or Pola-R-CHP (COALITION). Older/unfit patients with DLBCL might be particularly suitable for BsAb-containing combinations, such as the chemo-light combination of glofitamab plus Pola and rituximab (R-Pola-Glo), or epcoritamab plus rituximab (R)-mini-CHOP (dose-reduced cyclophosphamide, vincristine, doxorubicin and prednisone; EPCORE NHL-2). The 3‑year follow-up data from the STARGLO trial (gemcitabine/oxaliplatin ± glofitamab) in transplant-ineligible relapsed/refractory DLBCL patients (≥ 2L) underscored the durability of responses, in cases where complete response (CR) was achieved. In follicular lymphoma (FL), adding epcoritamab to rituximab plus lenalidomide (R2), the current standard of care (SOC) in 2L, produced impressive results, albeit limited by some additional toxicity, thus underlining the need for careful patient selection, close monitoring, and the use of anti-infective prophylaxis. Several chemo-free 1L strategies for patients with mantle cell lymphoma (MCL) were presented and showed encouraging results in terms of safety and efficacy including for high-risk cases (e.g., with a p53 mutated or blastoid variance). Specifically, they combined the second-generation BTK inhibitor (BTKi) acalabrutinib with the Bcl2 inhibitor venetoclax and rituximab (TrAVeRse), the BTKi zanubrutinib in combination with venetoclax and obinutuzumab (BOVen), or glofitamab plus lenalidomide and obinutuzumab (GLOVe). In essence, ASH2025 provided important data for further optimization of regimens including BsAb, targeted therapeutics, and reduced chemotherapy, especially in high-risk and older or unfit patients with lymphoma.