Tafasitamab Approaches EU Approval for Relapsed/Refractory Follicular Lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of tafasitamab (Minjuvi) plus lenalidomide (Revlimid) and rituximab (Rituxan) for use in adult patients with relapsed or refractory follicular lymphoma who had previously received at least 1 systemic therapy.¹

The positive opinion is supported by findings from the phase 3 inMIND trial (NCT04680052) in which the tafasitamab combination (n = 273) significantly reduced the risk of disease progression or death by 57% vs lenalidomide and rituximab alone (n = 275; HR, 0.43; 95% CI, 0.32-0.58; P < .0001).² At a median follow-up of 14.1 months, the median progression-free survival (PFS) with the addition of tafasitamab was 22.4 months (95% CI, 19.2-not evaluable [NE]) per investigator assessment vs 13.9 months (95% CI, 11.5-16.4) without.

Notably, independent review committee (IRC)–assessed PFS proved consistent with these results. The median PFS by IRC with the tafasitamab combination was not reached (NR; 95% CI, 19.3-NE) vs 16.0 months (95% CI, 13.9-21.1) with lenalidomide and rituximab alone (HR, 0.41; 95% CI, 0.29-0.56).

“In Europe, patients with relapsed or refractory [follicular lymphoma] after one prior treatment line currently receive a limited set of treatment options in the second-line setting,” Stefano Luminari, MD, professor of oncology at the University of Modena and Reggio Emilia, in Italy, and inMIND study investigator, stated in a news release.¹ “The approval of Minjuvi would introduce an important second-line chemotherapy-free alternative which has demonstrated a significant reduction in the risk of disease progression across a wide patient demographic.”

What was the trial design for inMIND?

The global, double-blind, placebo-controlled, phase 3 trial enrolled patients with grade 1 to 3A follicular lymphoma or marginal zone lymphoma who had previously received at least 1 line of therapy that must have included an anti-CD20 monoclonal antibody.² Patients were at least 18 years of age, had an ECOG performance status ranging from 0 to 2, and had not previously received lenalidomide paired with rituximab.

Study participants were randomly assigned 1:1 to receive 20 mg of oral lenalidomide daily on days 1 to 21 for 12 treatment cycles plus 375 mg/m2 of intravenous (IV) rituximab given once weekly for the first treatment cycle and every 4 weeks for cycles 2 to 5 with or without 12 mg/kg of IV tafasitamab intravenously every week for the first 3 cycles of treatment followed by every 2 weeks for cycles 4 to 12.

The trial’s primary end point was investigator-assessed PFS, and secondary end points comprised PET-complete response rate in the FDG-avid population as well as overall survival (OS). Investigators also examined IRC-assessed PFS, objective response rate (ORR), duration of response, safety, quality of life, and minimal residual disease. Exploratory end points included examination of time to next treatment (TTNT), B-cell recovery, Ig levels, and CD19 expression.

What were additional efficacy data from inMIND with tafasitamab?

Data from the study were presented at the 2024 ASH Annual Meeting and Exposition. Subgroup analyses showed that PFS benefit favored the tafasitamab regimen over the doublet irrespective of POD24 status and refractoriness to anti-CD20 antibody therapy. In those with POD24, the HR for PFS was 0.43 (95% CI, 0.27-0.69), and in those without POD24, the HR for PFS was 0.45 (95% CI, 0.31-0.65). In patients who were refractory to anti-CD20 antibody therapy, the HR for PFS was 0.44 (95% CI, 0.30-0.65); in those who were not refractory to this approach, the HR for PFS was also 0.44 (95% CI, 0.28-0.68).

Moreover, in the intention-to-treat population, the ORR with the triplet regimen was 83.5% (95% CI, 78.6%-87.7%) vs 72.4% (95% CI, 66.7%-77.6%) with the doublet (odds ratio, 2.0; 95% CI, 1.30-3.02; P = .0014). The median TNNT was NR (95% CI, NE-NE) with the tafasitamab combination vs 28.8 months (95% CI, 20.7-NE) with the control regimen (HR, 0.45; 95% CI, 0.31-0.64; P < .0001).

At the time of the analysis, the futility threshold for OS had not been crossed, indicative of a positive trend in the tafasitamab arm. The median OS was NR with the triplet (95% CI, 27.9-NE) or the doublet (95% CI, NE-NE; HR, 0.59; 95% CI, 0.31-1.13).

In a recent OncLive News Network program, Grzegorz S. Nowakowski, MD, a consultant in the Division of Hematology in the Department of Internal Medicine and the Enterprise Deputy Director of Clinical Research at Mayo Clinic Comprehensive Cancer Center, in Rochester, Minnesota, and Samuel Yamshon, MD, an assistant professor in the Department of Medicine at NYU Grossman School of Medicine, and medical director of Cellular Therapy Service at NYU Langone, further unpacked the data from the phase 3 inMIND trial with tafasitamab in relapsed/refractory follicular lymphoma.³

What was the safety profile of tafasitamab plus lenalidomide/rituximab in follicular lymphoma?

The most frequently experienced treatment-emergent adverse effects (TRAEs) in the triplet and doublet arms included neutropenia (48.5%; 45.2%), diarrhea (37.6%; 28.3%), COVID-19 (31.4%; 23.5%), constipation (29.2%; 24.6%), rash (21.9%; 21.3%), and fatigue (21.2%; 15.8%).² The most common TEAEs that were grade 3 or 4 included neutropenia (39.8%, triplet; 37.5%, doublet), pneumonia (8.4%; 5.1%), thrombocytopenia (6.2%; 7.4%), and decreased neutrophil count (5.8%; 6.6%).

What’s next for tafasitamab?

The European Commission is currently reviewing the positive opinion.¹ If cleared, this will signify the second indication for tafasitamab, according to Incyte, the drug developer. The agent possesses prior approval in Europe for use in combination with lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma.

Moreover, in June 2025, the FDA cleared tafasitamab-cxix (Monjuvi) plus lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma based on findings from inMIND.⁴ In an exclusive interview with OncLive®, Ajay K. Gopal, MD, FACP, underscored the clinical significance of the regulatory decision: “[Tafasitamab] offers another non-chemotherapy option for patients in the second line, where we didn’t really have this before. Most non-chemotherapy agents are approved in the third line or beyond, [this approval] offers an opportunity for a non-chemotherapy option that can improve PFS in the second line.”

Gopal is the medical director for Hematology, Malignancies/Hematology, the clinical research director for the Lymphoma Program, and an professor in the Clinical Research Division at Fred Hutch Cancer Center; professor of Hematology and Oncology in the Division of Hematology and Oncology and the Stephen Hans Petersdorf, MD, Endowed Chair in Cancer Care at the University of Washington Medicine.

References

1. Incyte announces positive CHMP opinion for Minjuvi (tafasitamab) for the treatment of relapsed or refractory follicular lymphoma (FL). News release. Incyte. November 17, 2025. Accessed November 17, 2025. https://www.businesswire.com/news/home/20251116608532/en/Incyte-Announces-Positive-CHMP-Opinion-for-Minjuvi-tafasitamab-for-the-Treatment-of-Relapsed-or-Refractory-Follicular-Lymphoma-FL
2. 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). Blood. 2024;144(suppl 2):LBA-1. doi:10.1182/blood-2024-212970
3. Nowakowski GS and Yamshon S. The phase 3 inMIND trial: Tafasitamab plus lenalidomide/rituximab in R/R follicular lymphoma. OncLive.com. February 4, 2025. Accessed November 17, 2025. https://www.onclive.com/view/the-phase-3-inmind-trial-tafasitamab-plus-lenalidomide-rituximab-in-r-r-follicular-lymphoma
4. Gopal AK. Dr Gopal on the FDA approval of tafasitamab in R/R follicular lymphoma. OncLive.com. August 13, 2025. Accessed November 17, 2025. https://www.onclive.com/view/dr-gopal-on-the-fda-approval-of-tafasitamab-in-r-r-follicular-lymphoma