Tafasitamab With Lenalidomide Plus Rituximab Improves PFS in Patients With R/R FL

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According to results from the phase 3 inMIND trial (NCT04680052), including tafasitamab-cxix (Monjuvi; Incyte Corp.) to a treatment regimen consisting of tenalidomide (Revlimid; Bristol Myers Squibb) plus rituximab (Rituxan; Genentech, Biogen) resulted in the significant and clinically meaningful improvement in progression-free survival (PFS) for patients with relapsed or refractory (R/R) follicular lymphoma (FL), said Laurie H. Sehn, MD, MPH, in a 2024 American Society of Hematology (ASH) Annual Meeting and Exposition presentation. The 3-drug regimen shows promise in both community and academic settings, supporting its potential as a new standard of care option for this patient population.¹

For patients with R/R FL, lenalidomide with rituximab is approved after at least 1 prior line of treatment. Although it is frequently used, immunotherapeutic approaches are preferred but there is a need to improve durability. Tafasitamab is a humanized monoclonal antibody (mAb) that targets CD19, induces direct cytotoxicity, and enhances NK cell and macrophage immune-mediated mechanisms. The agent was previously approved for use in R/R diffuse large B-cell lymphoma when combined with lenalidomide. According to Sehn, the goal of inMIND was to assess PFS in patients with FL while assessing the efficacy and safety of tafasitamab.^1,2

“[inMIND] is assessing the addition of tafasitamab, a CD19 mAB to a very commonly used backbone for patients with R/R FL called lenalidomide [with] rituximab. So, this is a study that's examining the addition of a mAb to a commonly used backbone of immunotherapy in R/R disease,” said Sehn, a hematology oncologist at BC Cancer Centre for Lymphoid Cancer, and the University of British Columbia, Canada, during the presentation.¹

The investigators enrolled 548 patients who were at least 18 years of age (median age: 64; range: 31-88 years) with R/R CD19+ and CD20+ FL, all of whom had grade I through IIIa disease. Additionally, all patients received at least 1 prior line of therapy, including an anti-CD20 mAb. All patients received standard dosing for 12 cycles of oral lenalidomide (20 mg/day on days 1-21) and intravenous (IV) rituximab (375 mg/m² on days 1-21), and afterwards, were randomly assigned to receive either 12 mg/kg of IV tafasitamab (n = 273) or matching placebo (n = 275) for up to 12 cycles (once per week for cycles 1-3, the once every 2 weeks for cycles 4-12). The study’s primary end point was PFS, which was assessed up to 6 years but planned for analysis after 174 events were observed.^1,2

“Key secondary end points included the PET-[complete response] rate as well as overall response rate [ORR] [and] PFS as confirmed by independent review committee [IRC]. Additional end points included [ORR], duration of response [DOR], safety, and quality of life, and there were numerous correlatives that are ongoing and planned, as well as time to next treatment [TTNT],” said Sehn.¹ "There is also an overall survival [OS] analysis plan with five years of follow up,."

Among the enrolled patients, the median number of prior lines of treatment was 1 (range: 1-10), and approximately 45% had 2 or more. Additionally, about 32% of patients had disease progression within 24 months and 43% were refractory to prior anti-CD20 mAb.¹

At the time of data cutoff, the tafasitamab and placebo arms received a median of 12 and 11 cycles of treatment, approximately 19% and 15% were still receiving treatment, and about 81% and 84% had discontinued, mostly because of treatment completion (54% and 43%) or disease progression (11% and 31%), respectively.¹

At a median follow-up of 14.1 months, the addition of tafasitamab to lenalidomide and rituximab was shown to significantly lower the risk of progression, relapse, or death compared with placebo, demonstrating a median PFS of 22.4 months compared with 13.9 months (HR [95% CI] 0.43 [0.32, 0.58]; P < .0001). Additionally, benefit was confirmed by IRC assessment (tafasitamab: median PFS not reached [NR] vs placebo: 16.0 months; HR [95% CI], 0.41 [0.29, 0.56]; P < .0001), and PFS benefit with tafasitamab was consistent in all prespecified subgroups that were analyzed.¹

Further, the data also showed that patients in the tafasitamab group had favorable PET-CR rates (49.4%) and ORR (83.5%) compared with placebo (PET-CR: 39.8%; ORR: 72.4%). Patients treated with tafasitamab also had improved DOR (median 21.2 months vs 13.6 months; HR [95% CI], 0.47 [0.33, 0.68]; P < .0001) and TTNT (median NR vs 28.8 months; HR [95% CI], 0.45 [0.31, 0.64]; P < .0001).

“At present, the data for OS was immature, but there was a trend in favor of tafasitamab. The safety profile was manageable and consistent with expected toxicities and comparable between the [treatment] arms,” said Sehn.¹

There was a similar rate of treatment-emergent adverse events (TEAEs; 99% vs 99%, grade 3 or 4 AEs (71% vs 69.5%), and serious AEs (36% vs 32%) observed in the tafasitamab and placebo groups, respectively. The most common grade 3 or 4 AEs with were neutropenia (40% vs 38%), pneumonia (8% vs 5%), thrombocytopenia (6% vs 7%), decreased neutrophils (6% vs 7%), COVID-19 (6% vs 2%), and COVID-19 pneumonia (5% vs 1%). TEAEs that led to discontinuation of treatment were reported by approximatley 11% and 7% of patients in the tafasitamab and placebo arms. Approximately 5.5% (n = 15) patients in the tafasitamab arm and 8.5% (n = 23) in the placebo arm died during the study, of which 2% (n = 5) and 6% (n = 17), respectively, were because of disease progression and 2% (n = 6) in each arm were a result of fatal AEs.¹

“Interestingly, this study is actually the first to validate the approach of combining 2 mAbs and anti-CD19 together with an anti-CD20 in patients with FL. Also, importantly, tafasitamab combined with lenalidomide and rituximab, can be administered easily in the community as well as academic settings, [representing] a potential new standard of care for patients with R/R FL,” concluded Sehn.¹

REFERENCES

1. Sehn, LH. Tafasitamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma: results from a phase 3 study (inMIND). Presented at: American Society of Hematology Annual Meeting and Exposition; San Diego, CA. December 7-10. Abstract: LBA-1.

2. A phase 3 study to assess efficacy and safety of tafasitamab plus lenalidomide and rituximab compared to placebo plus lenalidomide and rituximab in patients with relapsed/​refractory (R/​R) follicular lymphoma or marginal zone lymphoma. (InMIND). ClinicalTrials.gov identifier: NCT04680052. Updated August 15, 2024. Accessed December 9, 2024. https://clinicaltrials.gov/study/NCT04680052