Educational content on VJHemOnc is intended for healthcare professionals only. By visiting this website and accessing this information you confirm that you are a healthcare professional.
The Lymphoma Channel is supported with funding from AstraZeneca (Diamond), BMS (Gold), Johnson & Johnson (Gold), Takeda (Silver) and Galapagos (Bronze).
VJHemOnc is an independent medical education platform. Supporters, including channel supporters, have no influence over the production of content. The levels of sponsorship listed are reflective of the amount of funding given to support the channel.
The 2026 European Hematology Association (EHA) Congress delivered clinically relevant data across lymphoma. During the VJHemOnc Post-EHA Lymphoma Highlights webinar chaired by Krish Patel, MD, Sarah Cannon Research Institute, Nashville, TN, leading experts discussed a shortlisted selection of the abstracts presented at the meeting, highlighting emerging treatment strategies that could reshape standards of care in both aggressive and indolent non-Hodgkin lymphoma (NHL) subtypes.
From novel combinations in newly diagnosed high-risk diffuse large B-cell lymphoma (DLBCL) to new chemotherapy-free approaches in follicular lymphoma (FL), these studies underscore the continued momentum of immunotherapy, T-cell engagers, and targeted combinations in improving patient outcomes.
The FRONTMIND study: PFS benefit demonstrated with tafasitamab and lenalidomide plus R-CHOP
During the Post-EHA Lymphoma Highlights webinar, Umberto Vitolo, MD, Candiolo Cancer Institute, Candiolo, Italy, presented findings from the Phase III, double-blind, placebo-controlled FRONTMIND study (NCT04824092), which evaluated the addition of tafasitamab and lenalidomide to standard R-CHOP (Tafa-Len-R-CHOP) in patients with previously untreated high-risk DLBCL and high-grade B-cell lymphoma (HGBCL).
The study enrolled 899 patients with newly diagnosed, high-risk disease, who were randomized to either receive Tafa-Len-R-CHOP (n=448) or R-CHOP (n=451). Patients in the Tafa-Len-R-CHOP treatment group demonstrated a statistically significant improvement in progression-free survival (PFS) versus R-CHOP in the overall population (HR 0.75 [95% CI: 0.59–0.96]; p=0.019), meeting the primary endpoint. This translated to a two-year PFS rate of 71.1% versus 62.9%, respectively.1
Presenting the findings, Dr Vitolo emphasized the broad applicability of the benefit observed: “The primary endpoint of the study was met, and the addition of tafasitamab and lenalidomide to standard R-CHOP allowed us to reduce the risk of progression or death by 25%.”
Notably, the PFS advantage was observed across key patient subgroups, including both activated B-cell (ABC) and germinal center B-cell (GCB) molecular subtypes, demonstrating benefit across the major molecular cell-of-origin subtypes of DLBCL.1
A trend towards improved overall survival (OS) was observed (HR 0.85 [95% CI: 0.63–1.14]), although the data remain immature, with the final OS analysis planned after five years.1
Although complete response (CR) rates at the end of treatment were the same between treatment arms (65.2% in both groups), molecular response data provided further insight into treatment response. Measurable residual disease (MRD) negativity rates were substantially higher in the Tafa-Len-R-CHOP group, with 81.3% achieving MRD negativity compared with 66.7% in the comparator group (data shown during webinar presentation).1 This suggests deeper remissions that may underpin the observed PFS benefit.
Safety findings were consistent with expectations for the addition of two active agents. Any-grade treatment-emergent adverse events (TEAEs) were similar across the treatment arms (98.6% versus 97.1%). More grade ≥3 TEAEs occurred in the Tafa-Len-R-CHOP arm compared with the R-CHOP arm (86.7% versus 76.1%, respectively).1
The FRONTMIND results suggest that Tafa-Len-R-CHOP may represent a potential new first-line treatment option for patients with high-risk DLBCL and HGBCL, although longer follow-up will be needed to determine whether the improvement in PFS translates into an OS benefit.
EPCORE NHL-2: Epcoritamab plus R-mini-CHOP delivers durable remission in elderly patients with DLBCL
Older patients with DLBCL who are unable to tolerate full-dose R-CHOP represent a population with distinct treatment considerations, with frailty and/or comorbidities often influencing treatment selection. R-mini-CHOP remains a standard treatment option in this setting, although outcomes remain less favorable than those achieved in younger, fitter patients, and opportunities remain to improve long-term disease control.2
During the Post-EHA Lymphoma Highlights webinar, Chan Cheah, MBBS, Sir Charles Gairdner Hospital, Perth, Australia, presented results from EPCORE NHL-2 (NCT04663347), which evaluated the addition of the CD3xCD20 bispecific antibody epcoritamab to R-mini-CHOP in an older patient population.3
The Phase Ib/II study enrolled 28 newly diagnosed patients aged 75 years or older, or those aged 65 years or older with significant comorbidities. The median age was 81 years old (range 74–90); 89% of patients had de novo DLBCL, 46% had GCB and 39% had non-GCB. Patients received R-mini-CHOP in conjunction with epcoritamab in six, 21-day cycles, followed by two extra doses of epcoritamab.3
After a median follow-up of 33.4 months, the overall response rate (ORR) was 93%, with 86% of patients achieving a CR as best response. Among patients who completed treatment, 91% achieved a CR at the end of treatment. Median PFS and median OS were not reached, with estimated 2-year PFS and OS rates of 76% and 82%, respectively.3
Among evaluable patients, 95% achieved MRD negativity at any point during treatment. By Cycle 3 Day 1, 80% were MRD negative. At the second assessment (Cycle 6 Day 1), 12 of the 16 of patients maintained MRD negativity. High MRD negativity rates were also observed in patients with bulky disease (89%) and those with International Prognostic Index (IPI) scores of 3–5 (93%).3
The most common grade ≥3 TEAEs were neutropenia (43%), serious infections (32%), and anemia (14%), however, the safety profile was manageable and consistent with previous epcoritamab experience.3
These findings suggest that combining epcoritamab with R-mini-CHOP may represent a promising treatment approach for older adults with newly diagnosed DLBCL who are ineligible for full-dose R-CHOP, supporting further evaluation of bispecific antibody-based combinations in the frontline setting in this patient population.
EPCORE DLBCL-1: Epcoritamab demonstrates superior PFS versus chemoimmunotherapy in relapsed/refractory large B-cell lymphoma
Although CD3xCD20 bispecific antibodies have demonstrated activity in relapsed/refractory (R/R) DLBCL, prospective randomized comparisons with standard chemoimmunotherapy in R/R large B-cell lymphoma (LBCL) have been lacking.4
During EHA 2026 and the Post-EHA Lymphoma Highlights webinar, Christopher Fox, MBChB (Hons), MRCP, FRCPath, PhD, Nottingham University Hospitals NHS Trust, Nottingham, UK, presented primary results from the Phase III EPCORE DLBCL-1 trial (EudraCT No. 2020-003016-27), which evaluated epcoritamab monotherapy versus investigator’s choice of chemoimmunotherapy (CIT; rituximab plus gemcitabine/oxaliplatin [R-GemOx] or bendamustine plus rituximab [BR]) in patients with R/R LBCL.4
Eligible patients had CD20+ R/R LBCL, were ineligible for autologous stem cell transplantation (ASCT) or had relapsed after ASCT, and had received at least one prior line of systemic therapy. The study enrolled 483 patients who were randomized 1:1 to epcoritamab monotherapy (n=241) or CIT (n=242 [R-GemOx n=174; BR =68]).4
After a median follow-up of 43.2 months in the epcoritamab arm, and 42.3 months in the CIT arm, epcoritamab demonstrated a statistically significant improvement in PFS compared with CIT (HR 0.74 [95% CI: 0.60–0.92]; p=0.0059), meeting one of the study’s dual primary endpoints. The estimated 24-month PFS rates were 30% and 13%, respectively.4
Epcoritamab was also associated with higher CR rates compared with CIT (38% versus 26%; nominal p value 0.0032), while the median duration of response (DOR) was substantially longer (37 months versus 6 months).4
Although OS was not shown to be statistically significant between treatment arms (HR 0.96 [95% CI: 0.77–1.20]; 24-month OS: 38% versus 33%), interpretation of this endpoint was complicated by the greater use of subsequent bispecific antibodies, CAR T-cell therapy, or stem cell transplantation in the CIT arm compared with the epcoritamab arm (26% versus 6%, respectively), as well as COVID-19-related mortality during the study period.4
Safety findings were consistent with the established safety profile of epcoritamab. Grade 3–4 TEAEs occurred in 76% and 79% of patients receiving epcoritamab and CIT, respectively (data shown during webinar presentation). Grade 3–4 infections were more frequent with epcoritamab (30% versus 12%), while cytokine release syndrome (CRS) occurred in 53% of patients receiving epcoritamab, and was predominantly low-grade; 3% of patients reported Grade 3 CRS.4
The EPCORE DLBCL-1 trial represents the first randomized, Phase 3 trial to demonstrate a statistically significant PFS benefit with a CD3xCD20 bispecific antibody monotherapy compared with investigator’s choice of chemoimmunotherapy in R/R LBCL.4 Together with the improvements observed in CR rate and DOR, these findings further support the role of epcoritamab as a treatment option in this setting.
Mosunetuzumab plus lenalidomide: A chemotherapy-free approach in frontline follicular lymphoma
While chemotherapy remains the standard first-line treatment for patients with follicular lymphoma (FL) requiring systemic therapy,5 chemotherapy-free approaches are also being investigated.
During EHA 2026 and the Post-EHA Lymphoma Highlights webinar, Emmanuel Bachy, MD, PhD, Lyon Sud Hospital Center, Lyon, France, presented updated results from the Phase Ib/II CO41942 study (NCT04246086) evaluating subcutaneous mosunetuzumab plus lenalidomide induction therapy followed by mosunetuzumab maintenance in previously untreated FL.6
The study enrolled 43 patients with previously untreated FL requiring systemic treatment. The median age was 62 years, 47% of patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3–4, and 42% presented with bulky disease (data shown during webinar presentation). Patients received 12 cycles of mosunetuzumab plus lenalidomide induction, with eligible responders proceeding to optional mosunetuzumab maintenance.6
The best ORR was 90% and CR rate was 88%. After a median follow-up of 30.6 months, median DOR, PFS, and OS were not reached. The 24-month DOR, PFS and OS event-free rates were 94% (95% CI: 86–100), 87% (95% CI: 76–98), and 97% (95% CI: 92–100), respectively.6
The safety profile was manageable, with no new safety signals identified. 6 CRS occurred in 55.8% of patients during induction but was limited to Grade 1–2 events and was not observed during maintenance. No cases of immune effector-cell associated neurotoxicity syndrome (ICANS) or febrile neutropenia were reported.6
The combination of mosunetuzumab plus lenalidomide demonstrated durable responses and a manageable safety profile in patients with previously untreated, high-tumor-burden FL.6 These findings support the continued evaluation of chemotherapy-free treatment strategies in the first-line management of FL.
SOUNDTRACK-F1 trial: Initial results for surovatamig plus rituximab demonstrate deep responses in frontline FL
Alongside mosunetuzumab-based combinations, other bispecific antibody strategies are also being explored in the frontline treatment setting for FL. During EHA 2026 and the Post-EHA Lymphoma Highlights webinar, Chan Cheah presented initial safety run-in data from the ongoing Phase III SOUNDTRACK-F1 trial (NCT06549595).
This global, multicenter, open-label study is evaluating surovatamig, a CD19xCD3 bispecific antibody, in combination with rituximab. The safety run-in phase enrolled 43 patients with previously untreated, high-tumor-burden FL who were randomized to receive one of two target dose levels of surovatamig (2.4 mg or 7.2 mg) in combination with rituximab.7
Most patients presented with Ann Arbor stage IV disease (82% in the 2.4 mg group and 90% in the 7.2 mg group). High-risk FLIPI scores were reported in both cohorts (27% in the 2.4 mg group and 43% in the 7.2 mg group). At the data cutoff, the median follow-up across both cohorts was 6.3 months (range 3.9–14.6 months) and the median time on treatment was 6.0 months (range 3.7–13.4 months).7
Across both dose cohorts, the ORR was 95% in the 2.4 mg cohort and 100% in the 7.2 mg cohort, with CR rates of 84% and 85%, respectively. Among evaluable patients, 75% in the 2.4 mg group, and 100% in the 7.2 mg group were MRD negative.7
The safety profile was consistent across both dose levels, with no Grade 5 TEAEs or TEAEs leading to treatment discontinuations reported. CRS occurred in 36% and 38% of patients in the 2.4 mg and 7.2 mg cohorts, respectively, and was predominantly Grade 1 or 2. Two cases of ICANS were reported across both cohorts.7
The initial safety run-in results with surovatamig plus rituximab demonstrated deep responses and a manageable safety profile, supporting the selection of the 7.2 mg dose for continued evaluation in the ongoing SOUNDTRACK-F1 trial.7
Collectively, these studies highlight several major themes emerging across lymphoma research, including optimization of R-CHOP through novel combinations, expansion of bispecific antibodies into earlier treatment settings, and continued development of chemotherapy-free strategies. While many of these approaches require longer follow-up, the breadth of positive data presented at EHA 2026 suggests that treatment paradigms across both aggressive and indolent lymphomas may continue to evolve over the coming years.
References
-
Lenz G, Trněný M, Burke JM, et al. Tafasitamab plus lenalidomide and R-CHOP for patients with previously untreated diffuse large B-cell lymphoma (DLBCL): Results from the Phase 3 FRONTMIND study. Abstract S101. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
-
Ayers EC, Smith SM. Diffuse large B-cell lymphoma in the older and frail patient. Cancers, 2025;17(5):885.
- Belada D, Ďuraš J, Brody J, et al. Epcoritamab + R-MINI-CHOP results in 2-year remissions and high MRD-negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial. Abstract PF1007. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
- Fox CP, Inchiappa L, Ferhanoglu B, et al. Results from EPCORE DLBCL-1: Randomized Phase 3 study of epcoritamab (EPCOR) vs investigator’s choice chemoimmunotherapy (CIT) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Abstract S235. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
-
European Society for Medical Oncology (ESMO). ESMO Living Guideline: Follicular lymphoma – first-line disease management (advanced-stage disease). Updated 2025. Last access June 26 2026.
- Bachy E, Morschhauser F, Eyre TA, et al. Safety and efficacy of subcutaneous mosunetuzumab plus lenalidomide induction therapy followed by mosunetuzumab maintenance in previously untreated follicular lymphoma. Abstract S226. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
- Cheah CY, Menzies Wojtowicz M, Hyun Yoon D, et al. Surovatamig (AZD0486) plus rituximab in previously untreated follicular lymphoma (FL): Initial safety data from the Phase 3 SOUNDTRACK-F1 trial. Abstract S228. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
