Results from the phase III frontMIND trial show that adding tafasitamab and lenalidomide to R-CHOP for first-line treatment can reduce tumour progression in people with aggressive diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL).

The results are notable because the population included in the trial had high-intermediate risk and high-risk disease, which typically leads to poor outcomes.

The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, which took place May 29 to June 2 in Chicago. 

“While treatment for diffuse large B-cell lymphoma has improved in the last couple of years, many patients, especially those with high-risk disease, still face poor prognoses. The frontMIND study is significant as it is one of the few large phase 3 trials in first-line diffuse large B-cell lymphoma in which adding a therapy to R-CHOP improved clinical outcomes compared to R-CHOP alone, the standard regimen for over 20 years,” said lead study author Georg Lenz, MD, University Hospital Münster, Münster, Germany.

The frontMIND trial tested whether adding tafasitamab and lenalidomide to R-CHOP was a better first-line therapy than R-CHOP alone, particularly for people with higher risk DLBCL or HGBL and a poor prognosis. The trial included 899 people with high-intermediate or high-risk DLBCL or HGBL. The median age of participants was 65, and just over half were male. Participants were divided into 2 groups:

• 448 were assigned to receive tafasitamab and lenalidomide in addition to R-CHOP (tafasitamab and lenalidomide group).
• 451 were assigned to receive placebo and R-CHOP (control group).

Key Findings

• With a median follow-up time of 35.2 months, treatment with tafasitamab, lenalidomide, and R-CHOP reduced the risk of progression by 25%, compared to treatment with R-CHOP alone. The 3-year progression-free survival (PFS) was 67.3% in the tafasitamab and lenalidomide group, compared to 60.7% in the control group.
• Among participants whose diagnosis was centrally confirmed (773 of 899 participants), the combination treatment reduced the risk of progression by 32%.
• The authors report that the PFS benefit was seen in both ABC-type and GCB-type DLBCL. Data will be presented at the meeting. 
• Complete response (CR) and overall response rate (ORR) were similar in the two groups:
• CR was achieved in 65.2% of participants in both groups. 
• ORR was 80.4% in the tafasitamab and lenalidomide group vs. 76.1% in the control group.
• The difference in overall survival was not significant (81.7% in the tafasitamab and lenalidomide group vs. 78.9% in the control group at the time of reporting) but will continue to be monitored.

After starting treatment, more people in the tafasitamab and lenalidomide group experienced grade 3 and higher adverse events than in the control group—86.7% vs. 76.1%—but the issues were considered manageable. Infections and low numbers of white or red blood cells were more common in the tafasitamab and lenalidomide group than in the control group.

Adverse events led 25.7% of the tafasitamab and lenalidomide group and 17.9% of the control group to discontinue part of the treatment. About 5% in both groups stopped treatment altogether.  

“The frontMIND study represents only the second phase 3 randomized controlled trial in the last 25 years to demonstrate an improvement in primary efficacy outcome compared to the long-time global standard of care R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma.

Importantly, this improvement in progression-free survival is likely to lead to an improvement in long-term curative outcomes for patients with newly diagnosed diffuse large B-cell lymphoma,” said Krish Patel, MD, Executive Director of Hematologic Cancer Research at Sarah Cannon Research Institute and an ASCO Expert in lymphoma.

These data will be used to support the regulatory submissions seeking approval of tafasitamab and lenalidomide with R-CHOP as a first-line treatment in adults with newly diagnosed DLBCL and HGBL.

Source: ASCO