Tafasitamab/Lenalidomide/R-CHOP Improves PFS vs R-CHOP Alone in First-Line DLBCL

Tafasitamab-cxix (Monjuvi) in combination with lenalidomide (Revlimid) and R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) demonstrated a statistically significant improvement in progression-free survival (PFS) vs R-CHOP alone in the phase 3 frontMIND study (NCT04824092) evaluating the combination regimen as first-line therapy for adults with newly diagnosed diffuse large B-cell lymphoma (DLBCL).¹

The study met its primary end point of PFS by investigator assessment per Lugano 2014 criteria (HR, 0.75; 95% CI, 0.59-0.96; P = .019). The study also achieved its key secondary end point of event-free survival (EFS) by investigator assessment, and no new safety signals were observed with the addition of tafasitamab and lenalidomide to R-CHOP.

“The frontMIND study results highlight the potential benefit of combining tafasitamab and lenalidomide with R-CHOP as an effective treatment option, offering the possibility of cures for more newly diagnosed [patients with] DLBCL,” Steven Stein, MD, chief medical officer at Incyte, shared in a news release. “Despite improvement in treatment for patients with DLBCL, outcomes for many high-risk patients are not optimal. We look forward to working with regulatory authorities globally and to providing a new treatment option for patients in the future.”

Based on these results, Incyte announced plans to submit a supplemental Biologics License Application to the FDA in the first half of 2026 seeking approval of tafasitamab and lenalidomide in combination with R-CHOP for the treatment of adults with newly diagnosed DLBCL. Data from frontMIND are also expected to be presented at an upcoming medical meeting.

How was the frontMIND trial designed? What patient population was enrolled?

The frontMIND trial is a randomized, double-blind, placebo-controlled, global study that enrolled approximately 900 patients 18 to 80 years of age with previously untreated DLBCL.^1,2 The trial is evaluating tafasitamab plus lenalidomide in addition to R-CHOP vs R-CHOP alone, with efficacy and safety assessed across both arms.

The primary end point is investigator-assessed PFS per Lugano 2014 criteria, with key secondary end points including investigator-assessed EFS, as well as overall survival.

Major inclusion criteria for frontMIND included patients with previously untreated, local biopsy–proven, CD20-positive diffuse large B-cell lymphoma (DLBCL) per the 2016 World Health Organization classification.² This includes DLBCL not otherwise specified (NOS; germinal center B-cell or activated B-cell type), T-cell–rich large B-cell lymphoma (LBCL), Epstein–Barr virus–positive DLBCL NOS, ALK–positive LBCL, human herpesvirus 8–positive DLBCL NOS, high-grade B-cell lymphoma (HGBL) with MYC and BCL-2 and/or BCL-6 rearrangements (double-hit/triple-hit), HGBL-NOS, DLBCL coexistent with follicular lymphoma of any grade or with gastric/nongastric mucosa–associated lymphoid tissue lymphoma, or follicular lymphoma grade 3b.

Patients were required to be appropriate candidates for R-CHOP; those who, in the investigator’s judgment, warranted more intensive therapy for known double- or triple-hit disease were not eligible. Additional eligibility criteria included availability of archival or freshly collected tumor tissue for retrospective central pathology review, an International Prognostic index (IPI) score of 3 to 5 for patients older than 60 years of age or an age-adjusted IPI of 2 to 3 for patients 60 years of age or younger, a diagnosis-to-treatment interval of 28 days or fewer from first diagnostic biopsy specimen to cycle 1 day 1, an ECOG performance status 0 to 2, a left ventricular ejection fraction of at least 50%, adequate hematologic function, and protocol-specified reproductive risk mitigation requirements for both female and male participants.

What regulatory momentum has tafasitamab plus lenalidomide generated so far without R-CHOP in DLBCL management?

On August 1, 2020, tafasitamab received accelerated approval by the FDA in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL NOS, including DLBCL arising from low-grade lymphoma, who are ineligible for autologous stem cell transplant.³ This regulatory decision was based on findings from the phase 2 L-MIND study (NCT02399085), which demonstrated durable responses and a manageable safety profile with the combination. The European Medicines Agency also approved tafasitamab (Minjuvi) plus lenalidomide for this indication on August 27, 2021, based on the same findings from L-MIND.⁴

References

1. Incyte announces positive topline results from pivotal study of tafasitamab (Monjuvi/Minjuvi) as a first-line treatment for diffuse large B-cell lymphoma. Incyte. New Release. January 5, 2026. Accessed January 5, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-topline-results-pivotal-study-0
2. 2.Tafasitamab plus lenalidomide plus R-CHOP versus R-CHOP in newly diagnosed high-intermediate- and high-risk DLBCL patients (frontMIND). ClinicalTrials.gov. Updated September 8, 2025. Accessed January 5, 2026. https://www.clinicaltrials.gov/study/NCT04824092
3. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. Updated August 3, 2020. Accessed January 5, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tafasitamab-cxix-diffuse-large-b-cell-lymphoma
4. Incyte and MorphoSys announce the European Commission approval of Minjuvi (tafasitamab) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma. News release. Incyte. August 26, 2021. Accessed January 5, 2025. https://investor.incyte.com/news-releases/news-release-details/incyte-and-morphosys-announce-european-commission-approval