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SAN DIEGO -- Adding the humanized CD19-targeted monoclonal antibody tafasitamab (Monjuvi) to a backbone of lenalidomide (Revlimid) and rituximab (Rituxan) resulted in a significant and clinically meaningful improvement in progression-free survival (PFS) for patients with relapsed/refractory follicular lymphoma, the randomized phase III inMIND trial showed.

Patients who received the combination had a median PFS of 22.4 months compared with 13.9 months among patients treated with placebo plus lenalidomide and rituximab (HR 0.43, 95% CI 0.32-0.58, P<0.0001), reported Laurie Sehn, MD, MPH, of the BC Cancer Centre for Lymphoid Cancer and the University of British Columbia in Vancouver.

"This benefit was observed in all prespecified subgroups, including the high-risk subgroups of patients who are POD24 [had disease progression within 24 months], those who are refractory to prior anti-CD20 monoclonal antibodies, and patients receiving multiple prior lines of therapy," Sehn said during a press briefing in advance of a late-breaking abstract session at the American Society of Hematology annual meeting.

Noting that the combination involved both anti-CD19 and anti-CD20 monoclonal antibodies, press briefing moderator Mikkael Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, asked whether it could be a new standard of care for relapsed/refractory follicular lymphoma.

Sehn said the combination of lenalidomide and rituximab is commonly used in the relapsed/refractory setting and effective in patients, "but we can see in patients treated in the real world ... many of them are rituximab refractory from prior exposure from their chemoimmunotherapy and have high-risk features."

"The simple addition of tafasitamab to the lenalidomide/rituximab backbone really did significantly improve progression-free survival -- and I would say is clinically meaningful," she added. "So I do think that if patients are using lenalidomide/rituximab, it's sort of an easy addition ... to really get notable benefit."

Sehn also reported that the PET-complete response rate was 49.4% with added tafasitamab versus 39.8% without it (P=0.029) and the overall response rate was 83.5% versus 72.4%, respectively (P=0.0014). Median duration of response was 21.2 months with tafasitamab compared with 13.6 months in the placebo group (HR 0.47, 95% CI 0.33-0.68, P<0.0001).

Median time to next treatment was not reached with tafasitamab compared with 28.8 months in the placebo group (HR 0.45, 95% CI 0.31-0.64, P<0.0001). Despite overall survival data being immature, there was a trend favoring tafasitamab (HR 0.59, 95% CI 0.31-1.13), Sehn said.

Looking at the subgroups, median PFS among patients with POD24 was 19.2 months with tafasitamab versus 11.3 months with placebo (HR 0.43, 95% CI 0.27-0.69), and was 23.6 months versus 16 months, respectively, among those who did not have POD24 (HR 0.45, 95% CI 0.31-0.65).

Among patients who were refractory to anti-CD20 antibodies, the median PFS was 15 months with tafasitamab versus 8.6 months with placebo (HR 0.44, 95% CI 0.30-0.65), and 24 months and 18.2 months, respectively, among those who were not refractory (HR 0.44, 95% CI 0.28-0.68).

Sehn noted that inMIND was designed "based on expectations of the study," the results of which led to FDA approval of lenalidomide plus rituximab for the treatment of relapsed/refractory follicular lymphoma.

"It is noteworthy that the outcomes in the placebo arm of inMIND are actually poorer than in AUGMENT," she pointed out. "However, a careful comparison of the study populations demonstrates that patients enrolled in inMIND were much higher risk."

The was conducted in 26 countries and included 548 patients with follicular lymphoma. Median age was 64 years, 55% were men, 79% had intermediate- or high-risk disease based on the Follicular Lymphoma International Prognostic Index, and 83% had tumor burden per Groupe d'Etude des Lymphomes Folliculaires criteria.

The median number of prior lines of therapy was one, and 45% of patients had two or more prior lines of therapy. Nearly a third of patients had disease progression within 24 months, and 43% were refractory to prior anti-CD20 monoclonal antibodies.

The most common side effect was neutropenia, which occurred in 48.5% of patients in the tafasitamab arm and 45.2% in the placebo arm. The most common grade 3 or 4 treatment-emergent adverse event (TEAE) was also neutropenia, which occurred in 39.8% and 37.5%, respectively. There was also a higher rate of grade 3 or 4 pneumonia in the tafasitamab arm (8.4% vs 5.1%).

Dose delays or interruptions due to TEAEs occurred in 74% and 70% of the tafasitamab and placebo arms, respectively, while TEAEs led to treatment discontinuation in 11.7% and 7%.

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