Adding tafasitamab-cxix, an anti-CD19 monoclonal antibody, to lenalidomide and rituximab significantly prolonged progression-free survival in patients with relapsed or refractory follicular lymphoma, according to data presented at the 2025 European Hematology Association (EHA) Congress.¹

Results from the phase III inMIND trial demonstrated a significant reduction in the risk of disease progression, relapse, or death by 57% when tafasitamab was added to lenalidomide and rituximab, compared with placebo. The median progression-free survival was substantially improved at 22.4 months for patients receiving tafasitamab vs 13.9 months in the placebo group (hazard ratio [HR] = 0.43; P < .0001). The study authors emphasized that benefits were consistently observed across all key prespecified patient subgroups.

“The addition of tafasitamab to lenalidomide and rituximab resulted in significant and clinically meaningful improvement [in progression-free survival],” said lead study author Marek Trněný, MD, CSc, Professor of Medical Oncology and Head of the First Department of Medicine, Charles University, General Hospital in Prague. “These data validate the strategy of combining two monoclonal antibodies targeting CD19 and CD20 with an immunomodulatory agent, potentially establishing a new standard of care for patients with relapsed or refractory follicular lymphoma that is suitable for both academic and community treatment settings.”

“Although overall survival data remain immature, preliminary analyses suggest a favorable trend with tafasitamab treatment, warranting further long-term follow-up.”

— MAREK TRNĚNÝ, MD, CSc

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As Dr. Trněný reported, follicular lymphoma remains incurable despite therapeutic advances, with most patients eventually experiencing relapse after initial treatment. Immunotherapies such as rituximab and lenalidomide have significantly improved outcomes, he said, but still face limitations in treatment durability. Tafasitamab has previously demonstrated efficacy in diffuse large B-cell lymphoma, prompting investigation into its potential benefit in follicular lymphoma when combined with lenalidomide and rituximab.

Study Methods

The randomized, double-blind, placebo-controlled, international inMIND trial included 548 patients with relapsed or refractory follicular lymphoma who had received at least one prior systemic therapy including an anti-CD20 monoclonal antibody. Participants were randomly assigned 1:1 to receive either tafasitamab or placebo, both combined with lenalidomide for 12 cycles and rituximab for 4 cycles. Stratification factors included POD24 (progression of disease within 24 months of initial diagnosis) status, refractoriness to previous anti-CD20 therapy, and the number of prior treatment lines.

The primary endpoint was investigator-assessed progression-free survival. Secondary endpoints included overall response rate, complete metabolic response rate assessed by positron-emission tomography imaging, duration of response, time to next treatment, overall survival, and safety.

Improvement in Primary and Secondary Endpoints

As Dr. Trněný reported, the inMIND study met its primary endpoint, showing significant improvement in progression-free survival with tafasitamab compared with placebo (median, 22.4 vs 13.9 months; HR = 0.43). In addition, the overall response rate was higher with tafasitamab (84% vs 72%), and the rate of complete metabolic response also significantly increased with tafasitamab (49% vs 40%). The duration of response and the time to next treatment also favored the tafasitamab arm, according to Dr. Trněný, with the median time to next treatment not reached vs 29 months with placebo.

Safety profiles were similar between both treatment arms, with comparable rates of grade 3 or 4 adverse events (71% with tafasitamab vs 70% with placebo). Neutropenia was the most frequent severe event. Serious adverse events and treatment discontinuations from adverse events occurred at comparable rates in both groups.

“The benefit [of adding tafasitamab] was consistently observed across all key prespecified patient subgroups, including those with disease progression within 24 months of initial diagnosis, patients refractory to prior anti-CD20 monoclonal antibody therapies, and individuals previously treated with multiple lines of therapy,” Dr. Trněný concluded. “Although overall survival data remain immature, preliminary analyses suggest a favorable trend with tafasitamab treatment, warranting further long-term follow-up.”

DISCLOSURE: Dr. Trněný reported financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Gilead Sciences, Incyte Corporation, Janssen, MorphoSys, Roche, Takeda, and Celgene.

REFERENCE

1. Trněný M, Luminari S, Scholz CW, et al: Tafasitamab plus lenalidomide and rituximab for patients with relapsed or refractory follicular lymphoma: Results from the phase 3 inMIND study. EHA 2025 Congress. Abstract S230. Presented on June 14, 2025.

EXPERT POINT OF VIEW

P. Connor Johnson, MD, Attending Physician at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School, highlighted the significant clinical implications of the phase III inMIND trial, which compared the established second-line regimen of rituximab and lenalidomide with the addition of tafasitamab, an anti-CD19 monoclonal antibody. “The addition of tafasitamab appeared to significantly improve progression-free survival with what looks to me like a similar toxicity profile,” Dr. Johnson told The ASCO Post.

P. Connor Johnson, MD

Of note, he pointed out, discontinuation rates and dose reductions of lenalidomide were nearly identical between the two arms, which he found particularly encouraging. “If we have a regimen that improves progression-free survival without significantly increasing therapy-related toxicity, that’s something I will often turn to instead of the current standard, which for me and many providers is often rituximab and lenalidomide,” he stated.

CD19 Antigen Expression and Optimal Sequencing of Therapies

Dr. Johnson also addressed a common clinical concern about CD19 antigen expression, given tafasitamab’s mechanism of action and the potential downstream impact on eligibility for anti-CD19 chimeric antigen receptor (CAR) T-cell therapies. He referred to preliminary data from the International Conference on Malignant Lymphoma, noting that of eight tested patients, seven retained CD19 expression after treatment, whereas the eighth patient had a preexisting CD19-negative clone. Although these results are promising, Dr. Johnson emphasized the need for larger patient cohorts and continued follow-up to better inform treatment sequencing.

Looking forward, Dr. Johnson acknowledged the growing complexity of managing relapsed or refractory follicular lymphoma due to the increasing availability of effective therapies. “We have many exciting treatments available, including bispecific antibodies and CAR T cells potentially moving into earlier treatment lines,” he explained. “Understanding optimal sequencing of these therapies will be critical for patient care.”

“The results of the inMIND study are exciting for clinicians and patients alike,” Dr. Johnson concluded. “Tafasitamab, lenalidomide, and rituximab appears to be a regimen patients can receive close to home, and it doesn’t require highly specialized monitoring. This truly represents a practice-changing advance for many patients, including some patients in my practice.”

DISCLOSURE: Dr. Johnson has served as a consultant to ADC Therapeutics, AbbVie, AstraZeneca, Incyte, Novartis, Bristol Myers Squibb, and Seagen and has received research support from AstraZeneca, Regeneron, Novartis, and Incyte.