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The Hong Kong Special Administrative Region’s Department of Health has accepted for review a biologics license application seeking the approval of tafasitamab plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma.
The Hong Kong Special Administrative Region’s Department of Health has accepted for review a biologics license application (BLA) seeking the approval of tafasitamab (Monjuvi; Minjuvi) plus lenalidomide (Revlimid) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).1
“Today’s BLA acceptance marks another step forward after we received approval to conduct a registration trial for tafasitamab and lenalidomide from China’s National Medical Products Administration – reinforcing our commitment to bringing an innovative therapy like tafasitamab in combination with lenalidomide to potentially address the unmet need of eligible DLBCL patients in greater China,” Jasmine Cui, PhD, co-founder, chairwoman, and chief executive officer of InnoCare Pharma, stated in a press release.
In July 2020, the FDA granted an accelerated approval to tafasitamab-cxix for use in combination with lenalidomide in adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, and those who are not eligible to undergo autologous stem cell transplant.2
The regulatory decision was based on findings from the phase 2 L-MIND trial (NCT02399085). Early data from the trial showed that the doublet elicited an overall response rate (ORR) of 55%, which comprised a complete response (CR) rate of 37% and a partial response (PR) rate of 18%. The median duration of response (DOR) was 21.7 months.
The multicenter, open-label, single-arm, phase 2 L-MIND trial enrolled patients with histologically confirmed DLBCL who relapsed or who had refractory disease following prior treatment with 1 to 3 systemic regimens.3 To be eligible, patients needed to be at least 18 years of age, an ECOG performance status of 0 to 2, and measurable disease at baseline. They could not be candidates to receive high-dose chemotherapy and subsequent autologous stem cell transplantation.
Study participants received co-administered intravenous tafasitamab at 12 mg/kg and oral lenalidomide at 25 mg daily for up to twelve 28-day cycles followed by single-agent tafasitamab in those who achieved stable disease or better. Treatment was administered until disease progression.
The primary end point of the trial was ORR, and secondary end points comprised DOR, progression-free survival (PFS), and overall survival (OS).
A total of 80 patients received at least 1 dose of both agents and were examined for efficacy; 34 patients went on to receive tafasitamab monotherapy following the discontinuation of lenalidomide.4
The median age of patients was 72 years (range, 41-86), and had received a median of 2 prior lines of therapy (range, 1-4). All participants had received R-CHOP or chemoimmunotherapy before entering the study. Additionally, 18.5% of patients had primary refractory disease, 41.3% had disease refractory to rituximab (Rituxan), and 43.8% were refractory to their last therapy received. Most of the patients who were refractory to their last line of therapy had received 2 previous lines of treatment (71.4%); last previous line was chemotherapy in 94.4% of cases and rituximab in 80.0% of cases.
At a data cutoff of October 30, 2020, which had a follow-up of at least 35 months, the ORR per independent review committee (IRC) with the doublet was 57.5% (95% CI, 45.9%-68.5%), which included a CR rate of 40.0% and a PR rate of 17.5%. The median time to response as 2.1 months (range, 1.7-34.7), and the median time to CR was 6.8 months (range, 1.7-46.3).
Additionally, the median DOR per IRC assessment was 43.9 months (95% CI, 26.1–not reached [NR]); in those who achieved a CR with the combination, the median IRC-assessed DOR was not yet reached (95% CI, 43.9-NR).
At a median follow-up of 33.9 months, the median IRC-assessed PFS with the doublet was 11.6 months (95% CI, 6.3-45.7). At a median follow-up of 42.7 months, the median OS was 33.5 months (95% CI, 18.3-NR)
In those who achieved a CR with the combination, the median OS was not yet reached; the estimated 18-, 24, and 36-month OS rates were 96.9% (95% CI, 79.8%-99.6%), 90.6% (95% CI, 73.7%-96.9%), and 81.3% (95% CI, 62.9%-91.1%), respectively. In those who had a PR, the median OS was 22.5 months (95% CI, 8.6-NR); OS estimates at 18 months, 24 months, and 36 months were 59.8% (95% CI, 28.5%-81.0%), 42.7% (95% CI, 15.9%-67.5%), and 34.2% (95% CI, 10.7%-59.8%), respectively.
In those who received the doublet in the second-line setting (n = 40), the median PFS was 23.5 months (95% CI, 7.4-NR), the median DOR was 43.9 months (95% CI, 9.1-NR), and the median OS was 45.7 months (95% CI, 24.6-NR). In those who received the regimen as third- or later-line treatment (n = 40) experienced a median PFS of 7.6 months (95% CI, 2.7-NR), the median DOR was not yet reached (95% CI, 15.0-NR), and the median OS was 15.5 months (95% CI, 8.6-NR).
For the observational, retrospective RE-MIND trial (NCT04697160), investigators leveraged efficacy outcomes from patients who received tafasitamab plus lenalidomide in the L-MIND trial. Matched analysis sets were created for using an estimated propensity score–based method to compare outcomes of the doublet with patients treated with other systemic therapies for DLBCL pooled into a single cohort and cohorts comprising those who received common regimens.5
The hazard ratios for OS suggested a trend toward favoring tafasitamab plus lenalidomide in each matched analysis set overall, and in most patient subsets examined. In each subgroup analyzed, the trend favored enhanced OS with the doublet vs systemic approaches such as rituximab/lenalidomide and polatuzumab vedotin-piiq (Polivy) plus bendamustine and rituximab.