Tafasitamab Plus R-CHOP Improves PFS in First-Line DLBCL: Phase 3 Results

The pivotal phase 3 frontMIND study (NCT04824092) evaluating tafasitamab (Monjuvi) in combination with lenalidomide (Revlimid) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) met its primary end point.¹ The trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with the standard-of-care R-CHOP alone in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

The topline results represent a potential shift in the management of DLBCL, a common and aggressive form of non-Hodgkin lymphoma. For over 2 decades, R-CHOP has remained the foundational first-line therapy; however, approximately 40% of patients experience disease relapse or refractory progression, necessitating the development of more effective frontline regimens.

Study Design and Efficacy Data

The frontMIND study is a global, randomized, double-blind, placebo-controlled phase 3 trial. It enrolled 880 treatment-naive patients with high-intermediate and high-risk DLBCL (International Prognostic Index [IPI] scores of 3–5). Participants were randomized to receive either tafasitamab plus lenalidomide and R-CHOP or R-CHOP plus placebo.²

According to the data released, the addition of tafasitamab and lenalidomide to the R-CHOP backbone significantly prolonged the time patients lived without disease progression (HR, 0.75; 95% CI, 0.5–0.96; P =.019).¹

“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 DLBCL patients,” said Steven Stein, MD, chief medical officer at Incyte, 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.”

Safety and Tolerability

The safety profile observed in the frontMIND trial was consistent with the known safety signals of the individual agents. No new or unexpected safety concerns were identified when tafasitamab was integrated into the R-CHOP regimen. Previous studies of tafasitamab in the relapsed/refractory setting, such as the L-MIND trial (NCT02399085), highlighted common adverse events including neutropenia, fatigue, and diarrhea, which were generally manageable with supportive care and dose modifications.³

Mechanism of Action

Tafasitamab is a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody. By targeting the CD19 antigen, which is broadly expressed across the B-cell lineage, tafasitamab mediates B-cell lysis through apoptosis and immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis. The modification of the Fc region enhances its affinity for effector cells, theoretically providing more potent antitumor activity than non-modified antibodies.

When combined with lenalidomide, an immunomodulatory agent, the 2 drugs act synergistically to enhance ADCC activity. The frontMIND study sought to leverage this synergy earlier in the disease course to prevent early treatment failure.¹

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. News release. Incyte. January 5, 2026. Accessed January 5, 2026. https://tinyurl.com/3y9mepeu

2. Tafasitamab + lenalidomide + 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://clinicaltrials.gov/study/NCT04824092

3. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Epub 2020 Jun 5. PMID: 32511983.