Clinical Summary:

• Design/Population: The phase 3 FrontMIND trial compared tafasitamab plus lenalidomide and R-CHOP with R-CHOP alone in patients with previously untreated high-risk diffuse large B-cell lymphoma or high-grade B-cell lymphoma.
• Key Outcomes: Tafasitamab plus lenalidomide and R-CHOP significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 25% compared with R-CHOP. Event-free survival was also significantly improved while complete and overall response rates were similar between groups. 
• Clinical Relevance: These findings support tafasitamab plus lenalidomide and R-CHOP as a potential new first-line strategy for high-risk diffuse large B-cell lymphoma or high-grade B-cell lymphoma across cell-of-origin subtypes. However, the PFS benefit should be considered alongside higher rates of grade ≥3 and fatal treatment-emergent adverse events with the intensified regimen.

According to results from the phase 3 FrontMIND trial, adding tafasitamab and lenalidomide to R-CHOP significantly improved progression-free survival (PFS) compared in patients with previously untreated, high-risk diffuse large B-cell lymphoma or high-grade B-cell lymphoma. 

These results were presented by Jason Westin, MD, MD Anderson Cancer Center, Houston, Texas, at the at the Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, Texas.

In this double-blind, placebo-controlled trial, researchers enrolled 899 patients between 18 and 80 years of age with previously untreated diffuse large B-cell lymphoma or high-grade B-cell lymphoma, high-intermediate or high-risk disease, and an ECOG performance status of less than or equal to 2. Patients were randomized 1:1 to receive R-CHOP either alone (n = 451) or in combination with tafasitamab and lenalidomide (n = 448).  

The primary end point was investigator-assessed PFS. Key econdary end points included event-free survival (EFS), overall survival (OS), complete response, overall response rate (ORR), and safety. 

At a median follow-up of 35.2 months, tafasitamab plus lenalidomide and R-CHOP significantly improved PFS compared with R-CHOP, reducing the risk of disease progression or death by 25% (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59 to 0.96; P = .019). The 24-month PFS rates were 71.1% and with 62.9%, respectively. 

Among 773 patients with centrally confirmed lymphoma subtypes, the PFS benefit was more pronounced, with a 32% reduction in the risk of diease progression or death with tafasitamab plus lenalidomide and R-CHOP. The 24-month PFS rates were 72.7% and 62.2%, respectively. 

Point estimates generally favored the tafasitamab-containing regimen across prespecified subgroups, including patients with activated B-cell–like and germinal center B-cell–like molecular subtypes. 

EFS was also significantly improved with tafasitamab plus lenalidomide and R-CHOP. However, complete response and ORR were similar between treatment arms. 

At primary analysis, OS data numerically favored tafasitamab plus lenalidomide and R-CHOP (HR, 0.85; 95% CI, 0.63 to 1.14), although the confidence interval included the null. The final OS analysis is planned at 5 years. 

The study also evaluated whether frontline CD19-directed therapy affected CD19 expression at relapse. Among patients treated with tafasitamab plus lenalidomide and R-CHOP arm with lymphoma detected in biopsy tissue, all 14 patients remained CD19-positive. 

Any-grade treatment-emergent adverse events occurred in 98.6% of patients in the tafasitamab plus lenalidomide and R-CHOP arm and 97.1% of patients in the  R-CHOP arm. Grade ≥ 3 treatment-emergent adverse events were more frequent with the tafasitamab-containing regimen, occurring in 86.7% of patients compared with 76.1% of patients.  

Treatment-emergent adverse events resulted in discontinuation of all study drugs in 5.2% of patiens in the the tafasitamab plus lenalidomide and R-CHOP arm and 5.4% of patients in the R-CHOP arm. Treatment-emergent adverse events led to death in 5.9% and 3.8% of patients, respectively. Overall deaths occurred in 18.5% and 21.7% of patients, respectively.  

The FrontMIND findings demonstrate that intensifying first-line R-CHOP with tafasitamab and lenalidomide can improve PFS in patients with high-risk aggressive B-cell lymphoma without apparent loss of CD19 expression among the limited number of evaluable relapse biopsies. The increased incidence of severe and fatal treatment-emergent adverse events remains an important consideration when evaluating the benefit-risk profile of the regimen.

Source:

Westin J, Lenz G, Trnený M, et al. Primary outcomes from the phase 3 study of tafasitamab plus lenalidomide and R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (frontMIND). Presented at the SOHO Annual Meeting; September 9-12, 2026; Houston, Texas. Abstract ABCL-489.