Dr Smith on Implications of Data From the frontMIND Trial in DLBCL

The activity and the improved PFS suggest that [tafasitamab plus lenalidomide and R-CHOP] is overcoming some of the high-risk features [in this patient population].

Sonali M. Smith, MD, holder of the Elwood V. Jensen Professorship of Medicine and chief of the Section of Hematology/Oncology at University of Chicago Medicine, discussed implications of data from the phase 3 frontMIND trial (NCT04824092) evaluating tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) and R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with high-risk diffuse large B-cell lymphoma (DLBCL).

Findings presented at the 2026 ASCO Annual Meeting showed that treatment with tafasitamab plus lenalidomide and R-CHOP led to a 25% reduction in the risk of disease progression or death vs R-CHOP alone (HR, 0.75; 95% CI, 0.59-0.96; P = .0194). At a median follow-up of 35.2 months, patients who received the tafasitamab-based combination (n = 448) experienced a 2-year progression-free survival (PFS) rate of 71.1% compared with 62.9% with R-CHOP alone (n = 451). The 3-year PFS rates were 67.3% and 60.7%, respectively.

The tafasitamab-based regimen was also associated with an improvement in event-free survival (HR, 0.79; 95% CI, 0.64-0.97; P = .0260) and an overall survival trend favoring the experimental arm (HR, 0.85; 95% CI, 0.63-1.14; P = .2703).

Historically, clinical trials evaluating R-CHOP alone or in combination with another therapy have generally been conducted in all-comer DLBCL populations, according to Smith, who also explained that some studies have based enrollment on cell of disease origin. Notably, the frontMIND trial included patients with previously untreated DLBCL or high-grade B-cell lymphoma who had an International Prognostic Index (IPI) score of 3 to 5 (or an age-adjusted IPI score of 2 to 3 for patients 60 years of age and younger). Smith noted that this enrolled population comprised a true high-risk group based on IPI scores, and she added that high-grade B-cell lymphoma has also been associated with worsened outcomes when treated with R-CHOP alone.

Based on the data from frontMIND, tafasitamab plus lenalidomide and R-CHOP has the ability to overcome some of the high-risk features observed in the enrolled patient population, including non–germinal center cells of origin, Smith said.