4 Key Lymphoma Presentations From EHA 2026

EHA 2026 Lymphoma Presentations

Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Carla Casulo, MD, of University of Rochester, to discuss lymphoma highlights from the 31st European Hematology Association Annual Congress (EHA 2026). The doctors discussed data from the frontMIND, POLAR BEAR, and EPCORE FL-1 trials, as well as a retrospective analysis on high-dose methotrexate for CNS prophylaxis.

frontMIND: Adding Tafasitamab and Lenalidomide to R-CHOP for DLBCL

The frontMIND trial evaluated the addition of tafasitamab and lenalidomide to R-CHOP (Tafa-Len-R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for patients with DLBCL or high-grade B-cell lymphoma in the frontline setting. 

After a median follow-up of 35.2 months, Tafa-Len-R-CHOP significantly improved progression-free survival (PFS) versus R-CHOP alone for the overall population (HR, 0.75; 95% CI, 0.59-0.96; P = .019), with 24-month PFS rates of 71.1% and 62.9%, respectively. In patients with centrally confirmed lymphoma subtypes, the 24-month PFS rates were 72.7% with Tafa-Len-R-CHOP versus 62.2% with R-CHOP (HR, 0.68; 95% CI, 0.52-0.88). The benefit for Tafa-Len-R-CHOP was observed in both activated B-cell–like (HR, 0.59; 95% CI, 0.36-0.95) and germinal center B-cell–like (HR, 0.69; 95% CI, 0.40-1.19) subtypes. Tafa-Len-R-CHOP also significantly improved event-free survival, although complete response and overall response rate (ORR) at end of treatment were similar between arms.

The Tafa-Len-R-CHOP arm had an increased rate of treatment-related adverse events, and more data may be needed to truly determine the benefit from the addition of tafasitamab, particularly as tafasitamab requires weekly treatment, said Dr. Casulo. 

POLAR BEAR Describes New Frontline Regimen for Elderly Patients

The POLAR BEAR trial investigated an alternative to frontline dose-attenuated R-CHOP (R-mini-CHOP) for elderly or frail patients with DLBCL by substituting vincristine with polatuzumab vedotin (Pola-R-mini-CHP). Authors presented initial safety and pooled efficacy data after a median follow-up of 14.8 months.

The POLAR BEAR study enrolled 300 patients with a median age of 82 years. At the time of the analysis, there were 85 PFS events, including 35 deaths. The pooled 2-year PFS rate was 67% (95% CI, 60-73) and the pooled 2-year overall survival (OS) rate was 76% (95% CI, 70-81). The rate of grade 3 or higher adverse events was 30% with Pola-R-mini-CHP versus 36% with R-mini-CHOP. The rate of hematologic toxicity was comparable between the arms, although the Pola-R-mini-CHP arm had a lower rate of grade 3 or higher infections (7.3% vs 12.7%) and a higher rate of grade 2 or higher gastrointestinal toxicity (6% vs 3.3%). Peripheral neuropathy, primarily grade 1 or 2, occurred in 10.7% of the Pola-R-mini-CHP arm versus 17.3% of the R-mini-CHOP arm.

The PFS rate achieved with Pola-R-mini-CHP is an improvement compared with historical controls and this could emerge as a new standard for elderly patients, although polatuzumab vedotin–related toxicities are still a challenge, said Dr. Casulo.

The End of High-Dose Methotrexate for CNS Prophylaxis

Two recent retrospective analyses suggested high-dose methotrexate does not meaningfully reduce CNS relapse rates in high-risk large B-cell lymphoma. However, treatment guidelines still recommend considering methotrexate in ultra–high-risk populations. To challenge this recommendation, investigators analyzed the effect of high-dose methotrexate in patients from the retrospective studies who met ultra–high-risk criteria. Their findings were presented at EHA 2026. 

The overall analysis included 1923 patients with ultra–high-risk disease, of which 872 received high-dose methotrexate and 1051 did not. The population had a median age of 66 years (range, 18-86) and a median follow-up of 54.4 months (interquartile range, 31.9-85.2). Overall, there was no significant difference in 3-year CNS relapse rates between the methotrexate and non-methotrexate populations (9.3% vs 8.1%; adjusted HR, 1.10; 95% CI, 0.8-1.53). There was also no significant difference between isolated CNS relapse subgroups (5.9% vs 5.7%; adjusted HR, 1.01; 95% CI, 0.68-1.50).

The investigators also performed a landmark analysis of 1529 patients who had no events at 6 months, of which 773 received methotrexate and 782 did not. In this population, 3-year OS was 83.8% (95% CI, 80.5-86.6) with methotrexate versus 79.7% (95% CI, 76.6-82.4) without methotrexate. In addition, there was no difference in 3-year CNS relapse rate in ultra–high-risk patients (6.6% vs 6.7%; adjusted HR, 0.89; 95% CI, 0.58-1.35), according to the presentation. These data ultimately support dropping high-dose methotrexate as CNS prophylaxis in patients with high-risk B-cell lymphoma moving forward, said Dr. Casulo.

Epcoritamab Outcomes for EPCORE FL-1 Subgroups

Previously the phase 3 EPCORE FL-1 trial showed epcoritamab plus rituximab and lenalidomide improved ORR and PFS versus rituximab and lenalidomide alone in patients with relapsed or refractory follicular lymphoma. At EHA 2026, authors presented subgroup analyses for clinically relevant subgroups, including baseline Follicular Lymphoma International Prognostic Index (FLIPI) scores, progression of disease within 24 months of frontline treatment initiation (POD24), and non-Hodgkin lymphoma (NHL)-5 comorbidity score.

The epcoritamab regimen had a higher ORR and complete response (CR) rate versus rituximab plus lenalidomide in both FLIPI 0-2 and FLIPI 3-5 score subgroups, and hazard ratios for PFS favored epcoritamab across FLIPI subgroups. In non-POD24 patients, epcoritamab had improved ORR (96.2% vs 85.4%) and CR rate (85.5% vs 57.6%), and was again favored for PFS (HR, 0.17; 95% CI, 0.09-0.32). A similar trend was reported for POD24 subgroups. Epcoritamab was also favored for ORR, CR, and PFS among NHL-5 low and NHL-5 high or intermediate subgroups, according to the report.