The addition of tafasitamab, a CD19 monoclonal antibody, to the commonly used lenalidomide and rituximab backbone significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma, according to data presented during the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition.¹

Primary results of the phase III inMIND trial demonstrated a median progression-free survival of 22.4 months with tafasitamab vs 13.9 months in the placebo arm, representing a 57% reduction in the risk of disease progression, relapse, or death (hazard ratio [HR] = 0.43, P < .0001). Additionally, the overall response rate improved from 72.4% to 83.5% with tafasitamab, and positron-emission tomography (PET)/complete response rates increased from 39.8% to 49.4%. These findings represent a significant advance in the treatment of this challenging patient population and suggest a potential new standard of care, authors of the study noted.

“These results demonstrate the robust efficacy of tafasitamab in combination with lenalidomide and rituximab, showing significant improvement in progression-free survival across all patient subgroups, including those with high-risk disease,” said lead study author Laurie H. Sehn, MD, MPH, Clinical Professor at the BC Cancer Centre for Lymphoid Cancer and the University of British Columbia. “The combination of tafasitamab, lenalidomide, and rituximab also significantly improved overall response rates and time to next treatment without compromising safety or tolerability.”

“This combination is not only effective but also practical, as it can be administered in both community and academic settings....”

— Laurie H. Sehn, MD, MPH

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As Dr. Sehn explained, relapsed or refractory follicular lymphoma remains a challenging disease, particularly for high-risk patients who experience progression in the first 2 years (POD24) or resistance to prior anti-CD20 monoclonal antibody therapy. The inMIND study sought to evaluate the addition of tafasitamab to the established lenalidomide and rituximab regimen to address unmet needs in this patient population.

“This study validates the concept of combining two monoclonal antibodies, targeting both CD19 and CD20, alongside lenalidomide, an immunomodulatory agent, to enhance outcomes in follicular lymphoma,” explained Dr. Sehn.

Study Design

The randomized, double-blind, placebo-controlled, international phase III trial enrolled 548 patients with follicular lymphoma (grades 1–3A) or marginal zone lymphoma who had received at least one prior line of therapy, including an anti-CD20 monoclonal antibody. Patients were stratified by key risk factors, including POD24 status, refractoriness to prior therapy, and the number of prior treatment lines (one vs more than one). All participants received lenalidomide and rituximab for 12 cycles and were randomly assigned 1:1 to receive either tafasitamab (12 mg/kg intravenously) or placebo for up to 12 cycles.

The primary endpoint was investigator-assessed progression-free survival, with secondary endpoints including PET/complete response rate, overall response rate, duration of response, quality of life, and time to next treatment.

Improved Outcomes Across Risk Groups

With a median follow-up of 14.1 months, the inMIND trial achieved its primary endpoint, showing a significant improvement in progression-free survival with tafasitamab. Median progression-free survival was 22.4 months in the tafasitamab arm compared with 13.9 months in the placebo arm, representing a 57% reduction in risk (HR = 0.43, P < .0001).

Subgroup analyses showed consistent benefits across all prespecified groups, including high-risk patients. Patients with POD24 experienced significant progression-free survival improvement, as did those who were refractory to prior anti-CD20 monoclonal antibody therapy. Both patients with one prior line of therapy and those with multiple prior lines demonstrated meaningful progression-free survival improvements, Dr. Sehn added.

In addition to progression-free survival, the PET/complete response rate in the tafasitamab arm increased from 39.8% to 49.4%, and the overall response rate rose from 72.4% to 83.5%. The duration of response and time to next treatment were also significantly improved, with the median time to next treatment not yet reached in the tafasitamab arm vs 28.8 months in the placebo arm.

“These findings are particularly impactful for high-risk populations, where achieving durable responses has been a long-standing challenge,” Dr. Sehn noted.

Safety and Tolerability

The safety profile of tafasitamab was also reported to be manageable and consistent with expectations. The most common high-grade toxicity was neutropenia, occurring in 39.8% of tafasitamab-treated patients and 37.5% of placebo-treated patients. Pneumonia was slightly more frequent in the tafasitamab arm (8.4% vs 5.1%), as was COVID-19 infection (5.8% vs. 2.2%), but treatment discontinuation because of adverse events was similar between arms (11% vs 7%).

Of note, the addition of tafasitamab did not seem to interfere with the administration of lenalidomide and rituximab, as dose reductions and interruptions were comparable between the two arms, according to Dr. Sehn. She emphasized tafasitamab’s potential to transform the treatment landscape for relapsed or refractory follicular lymphoma. “This combination is not only effective but also practical, as it can be administered in both community and academic settings, representing a potential new standard of care for patients with relapsed or refractory follicular lymphoma,” Dr. Sehn concluded.

Ongoing follow-up will further evaluate overall survival and long-term outcomes, but the current results underscore tafasitamab’s role in improving outcomes for patients with relapsed or refractory follicular lymphoma. 

DISCLOSURE: Dr. Sehn reported financial relationships with AbbVie, Ascerta, Amgen, Apobiologix, AstraZeneca, BeiGene, BMS/Celgene, Debiopharm, F. Hoffmann–La Roche Ltd, Genentech, Genmab, Kite/Gilead, Incyte, Janssen, Karyopharm Therapeutics, Lundbeck, Merck, MorphoSys, Novartis, Roche, Sandoz, Seagen, Seattle Genetics, Takeda, Teva, TG Therapeutics, and Verastem Oncology.

REFERENCE

1. Sehn LH, Luminari S, Scholz CW, et al: Tafasitamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma: Results from a phase 3 study (inMIND). 2024 ASH Annual Meeting & Exposition. Abstract LBA-1. Presented December 10, 2024.

EXPERT POINT OF VIEW

Carrie Ho, MD, a hematologist/oncologist at UCSF Health, underscored the significance of the inMIND trial findings for patients with relapsed or refractory follicular lymphoma, particularly those with high-risk disease features.

“Achieving durable responses remains a major challenge for high-risk patients, such as those with progression of disease within 24 months [POD24] or who are refractory to anti-CD20 therapies,” Dr. Ho told The ASCO Post. “The inMIND trial is an important step forward, demonstrating that adding tafasitamab to lenalidomide and rituximab can meaningfully improve progression-free survival and response rates, even in these difficult-to-treat populations.”

Carrie Ho, MD

The double-blind, placebo-controlled phase III trial demonstrated a 57% reduction in the risk of disease progression, relapse, or death with the addition of tafasitamab to lenalidomide and rituximab compared with placebo (median progression-free survival: 22.4 vs 13.9 months; hazard ratio = 0.43 [0.32–0.58]). “Secondary endpoints, including overall response rate, complete response, and duration of response, also showed significant improvement, highlighting the potential of this dual-antibody approach targeting CD19 and CD20,” Dr. Ho added. “Of note, the addition of tafasitamab did not lead to a substantial increase in toxicities, with only modest increases in the rates of diarrhea and COVID-19–related events.”

Dr. Ho noted that although overall survival data are still maturing, current evidence suggests that tafasitamab combined with lenalidomide and rituximab may prove to be a valuable addition to the treatment armamentarium for relapsed or refractory follicular lymphoma.

What Next?

“Looking ahead, the integration of novel therapies such as tafasitamab, alongside the anticipated adoption of bispecific antibodies in earlier lines of treatment, raises important questions about sequencing and long-term outcomes,” Dr. Ho explained. “The potential effects of prior therapies on immune fitness and antigen expression, such as CD19 or CD20 downregulation, will need to be carefully considered to optimize the efficacy of subsequent treatments, including chimeric antigen receptor T-cell therapy.”

Finally, Dr. Ho emphasized the importance of preserving immune functionality, as tafasitamab and bispecific antibodies are incorporated into earlier treatment settings. She noted this will be critical to achieving durable responses across the treatment continuum.

“In summary, although longer follow-up is needed to fully define the role of tafasitamab plus lenalidomide and rituximab, this combination holds great promise for improving outcomes in relapsed or refractory follicular lymphoma,” Dr. Ho concluded. “Its emergence represents an important step forward in advancing follicular lymphoma treatment and underscores the ongoing evolution toward more targeted, chemotherapy-free strategies.” 

DISCLOSURE: Dr. Ho reported no conflicts of interest.