Tafasitamab Combo Prolongs Progression vs R-CHOP Alone in BCL Groups

The addition of tafasitamab (Monjuvi) and lenalidomide (Revlimid) to a regimen consisting of rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) conferred a significant reduction in the risk of disease progression or death compared with R-CHOP alone in patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), according to findings from a primary analysis of the phase 3 frontMIND trial (NCT04824092) presented in an oral abstract session the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

At the data cut-off date of October 20, 2025, the trial's primary end point of investigator-assessed progression-free survival (PFS) was met, with a hazard ratio (HR) of 0.75 (95% CI, 0.59-0.96; P =.019) in the overall intention-to-treat population after a median follow-up of 35.2 months. In patients with centrally confirmed lymphoma subtypes (n = 773), the PFS HR was 0.68 (95% CI, 0.52-0.88), with a 24-month PFS rate of 72.7% vs 62.2% in favor of tafasitamab plus lenalidomide and R-CHOP (Tafa-Len-R-CHOP).

“We believe that the combination of [Tafa-Len-R-CHOP] is a potential new standard for frontline therapy for patients with intermediate or high-risk [DLBCL] or [HGBL],” lead investigator Georg Lenz, MD, university professor in the Department of Medicine A – Haematology and Oncology of the University Hospital Münster, Germany, stated during a pre-meeting press briefing on the findings.

frontMIND Study Design

frontMIND was a randomized, double-blind, placebo-controlled, global phase 3 trial which enrolled 899 adults aged 18 to 80 years with previously untreated, high-intermediate– or high-risk DLBCL or HGBL, defined as International Prognostic Index [IPI] score 3–5; age-adjusted IPI 2–3 for patients aged ≤60 years.² Patients also had an ECOG performance status of 0 to 2 and were required to have at least 1 measurable PET-positive lesion within 28 days of diagnostic biopsy.

Patients were randomly assigned 1:1 to receive Tafa-Len-R-CHOP (n = 448) or R-CHOP with placebo (n = 451) for six 21-day cycles. Stratification factors included IPI/age-adjusted IPI score and geographic region.

The primary end point was investigator-assessed PFS; key secondary end points included event-free survival (EFS), overall survival (OS), complete response (CR) rate, and overall response rate (ORR).

Supplemental Efficacy Data

The 24-month PFS rate was 71.1% with Tafa-Len-R-CHOP vs 62.9% with R-CHOP, representing an absolute difference of 8.2 percentage points; at 36 months, the rates were 67.3% vs 60.7%, respectively, with a delta of 6.6%. The median PFS had not been reached as of the data cut-off.

Among patients with centrally confirmed lymphoma subtypes, the 24-month PFS rate was 72.7% with Tafa-Len-R-CHOP vs 62.2% with R-CHOP, a difference of 10.5 percentage points, with an HR of 0.68 (95% CI, 0.52–0.88). According to the investigators, a PFS benefit with Tafa-Len-R-CHOP was observed across both activated B-cell–like (ABC) and germinal center B-cell–like (GCB) molecular cell-of-origin subtypes.

Tafa-Len-R-CHOP also significantly improved EFS compared with R-CHOP (HR, 0.79; 95% CI, 0.64-0.97; P =.026). The 24-month EFS rate was 65.0% vs 56.7%, and the 36-month EFS rate was 61.2% vs 54.8% in the Tafa-Len-R-CHOP and R-CHOP arms, respectively.

CR and ORR were similar between treatment arms. An interim OS analysis showed a numerical trend in favor of Tafa-Len-R-CHOP, with an HR of 0.85 (95% CI, 0.63-1.14; P =.2703); the 24-month OS rates were 84.1% vs 80.5% and the 36-month rates were 81.1% vs 77.8% with Tafa-Len-R-CHOP vs R-CHOP, respectively. Overall, there were fewer deaths in the Tafa-Len-R-CHOP arm (n = 82; 18.5%) than in the R-CHOP arm (n = 97; 21.7%); a final OS analysis is planned at 5 years.

Safety Findings

The addition of tafasitamab and lenalidomide to R-CHOP was associated with a manageable but increased toxicity burden compared with R-CHOP alone. Any-grade treatment-emergent adverse events (TEAEs) were similar across arms (98.6% vs 97.1%). Grade ≥3 TEAEs occurred more frequently in the Tafa-Len-R-CHOP arm (86.7% vs 76.1%). The most common AEs were cytopenias and infectious events, consistent with the known safety profiles of the individual agents.

Discontinuations due to TEAEs occurred in 5.2% of patients in the Tafa-Len-R-CHOP arm vs 5.4% in the R-CHOP arm. Deaths were reported in 18.5% vs 21.7% of patients, respectively. Importantly, the addition of tafasitamab and lenalidomide did not appear to compromise the delivery of the R-CHOP backbone; median relative dose intensities were high and equivalent between the 2 groups for all R-CHOP components across 6 cycles.

Implications and Future Directions

With the primary end point of PFS met, the data now position Tafa-Len-R-CHOP as a regimen capable of improving upon the decades-long standard of R-CHOP in patients with high-risk, newly diagnosed DLBCL or HGBL. Notably, the PFS benefit was observed regardless of molecular cell-of-origin subtype—a finding of particular clinical interest given that prior attempts to improve on R-CHOP have often shown differential efficacy by subtype.

When asked about where the regimen fits into the broader treatment landscape alongside chimeric antigen receptor T-cell (CAR T) therapy, Lenz noted that further data are needed to fully characterize the interaction between prior tafasitamab exposure and subsequent CAR T-cell efficacy, but that preliminary observations from frontMIND are reassuring.

“From what we know with tafasitamab, it does not impair subsequent CAR T-cell therapies. That’s also the preliminary data of the frontMIND study; when we looked at those patients relapsing and being treated with a CAR T-cell therapy, they still expressed CD19, and they still responded in the ballpark of what you would expect,” Lenz explained. “So I would assume we're not impairing CAR-T cell efficacy, but obviously we need much more data to answer that in a solid manner.”

Regarding next steps, Incyte, the developer of tafasitamab, has previously announced plans to file a supplemental biologics license application to the FDA for Tafa-Len-R-CHOP for the first-line treatment of adults with newly diagnosed DLBCL.³

Disclosures: Lenz reported honoraria from Abbvie, ADC Therapeutics, AstraZeneca, BeiGene/BeOne, Bristol-Myers Squibb, Exscientia, Genmab, Gilead Sciences, GlaxoSmithKline, Hexal, Immagene/Flindr, Incyte, Lilly, Miltenyi Biotec, MSD, Novartis; Pentixapharm, Pierre Fabre, Roche/Genentech, SOBI; a consulting or advisory role with Abbvie, ADC Therapeutics, AstraZeneca, BeiGene/BeONE, Bristol-Myers Squibb, Exscientia, Genmab, Gilead Sciences, GlaxoSmithKline, Hexal, Immagene/Flindr, Incyte, Lilly, Miltenyi Biotec, MSD, Novartis, Pentixapharm, Pierre Fabre, Roche/Genentech, SOBI; receipt of institutional research funding from Abbvie, AstraZeneca, Gilead Sciences, Novartis, Roche/Genentech, SOBI; and expert testimony for Roche.

References

1. Lenz, G, Trněný M, Burke JM, et al. frontMIND: phase 3 study of tafasitamab (Tafa) plus lenalidomide (Len) and R-CHOP for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2026;44(suppl 17):LBA7000. doi:10.1200/JCO.2026.44.17_suppl.LBA7000

2. Tafasitamab + lenalidomide + R-CHOP versus R-CHOP in newly diagnosed high-intermediate and high risk DLBCL patients (frontMIND). ClinicalTrials.gov. Updated April 1, 2026. Accessed May 30, 2026. https://clinicaltrials.gov/study/NCT04824092

3. Incyte announces positive topline results from pivotal study of tafasitamab (Monjuvi®/Minjuvi®) as a first-line treatment for diffuse large B-cell lymphoma. News release. Incyte. January 5, 2026. Accessed May 30, 2026. https://tinyurl.com/3kcd54h2