Patients with autologous stem cell transplant–ineligible relapsed/refractory diffuse large B-cell lymphoma appear to benefit from treatment with tafasitamab and lenalidomide.
Treatment with tafasitamab (Monjuvi) and lenalidomide (Revlimid) provided an overall survival (OS) benefit vs standard options in a population of patients with autologous stem cell transplant (ASCT)–ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to findings from an expanded analysis of RE-MIND2 study (NCT04697160) that was presented at the 2021 American Society of Hematology Annual Meeting and Symposium.
The combination of prolonged median overall survival (OS) compared with other standard options for patients with, according to a closely matched.
For the analysis, investigators retrospectively collected real-world data were closely matched and compared with findings from the pivotal, observational, retrospective L-MIND study, a single-arm trial that led to an FDA accelerated approval of tafasitamab plus lenalidomide in July 2020. In the analysis, there was a statistically significant 56% reduction in the risk of death with tafasitamab plus lenalidomide compared with either polatuzumab vedotin (Polivy) plus bendamustine and rituximab (Rituxan; Pola-BR) or rituximab plus lenalidomide (R2). OS data were similar with tafasitamab plus lenalidomide and chimeric antigen receptor (CAR)-modified T-cell therapies.
“It is clear that we aren't able to compare efficacy of these regimens in randomized studies, it is just not possible, in particular since some of the historical control arms would not be of scientific interest and not very active,” lead author Grzegorz S. Nowakowski, MD, of the Division of Hematology, Mayo Clinic, said during a presentation of the results. “Real-world data can provide the momentum to compare the efficacy of these regimens with close patient-based matching.”
For the global RE-MIND2 study, the comparator arms were selected by examining the treatments recommended by the National Comprehensive Cancer Network and ESMO guidelines. Patients were matched across 9 variables, including age, number of prior therapies, prior ASCT, ECOG performance status, and refractoriness (primary refractory or refractory to last therapy line). There was a high degree of covariate balance between those treated with tafasitamab plus lenalidomide in L-MIND and the other therapeutic cohorts, said Nowakowski. “This strategy resulted in an excellent match, it is nearly perfect for all the covariates in this study,” he said.
After the matching between L-MIND and real-world data, the cohorts contained 24, 33, and 37 patients in each arm for tafasitamab plus lenalidomide and Pola-BR, R2, and CAR T cells, respectively. The median follow-up duration in L-MIND for tafasitamab plus lenalidomide was 32 months. The median follow-up was 16.6 months, 13.4 months, and 10.2 months in the Pola-BR, R2, and CAR T cell cohorts, respectively.
The median OS with tafasitamab plus lenalidomide was 20.1 months (95% Cim 8.6–not reached [NR] compared with 7.2 months (95% CI, 4.9-11.6) with Pola-BR in matched patients with DLBCL (HR, 0.441; 95% CI, 0.203-0.956; P = .0340). The median OS was 24.5 months (95% CI, 12.1-NR) with tafasitamab plus lenalidomide in patients who matched those treated with R2 in the real-world setting compared with 7.4 months (95% CI, 4.2-11.1) with R2 (HR, 0.435; 95% CI, 0.224-0.847; P = .0122). In the CAR T-cell comparison, the median OS was 22.5 months with tafasitamab plus lenalidomide compared with 15.0 months (HR, 0.953; 95% CI, 0.475-1.913; P = .8915).
In the Pola-BR comparison, the objective response rate (ORR) was 62.5% (95% CI, 40.6-81.2) with tafasitamab plus lenalidomide compared with 58.3% (95% CI, 36.6-77.9) with Pola-BR (P = 1.000). The complete response (CR) rates were 29.2% (95% CI 12.8-51.1) vs 20.8% (95% CI, 7.1-42.2) and the duration of response (DOR) was 17.7 months (95% CI, 3.6-34.8) vs 2.3 months (95% CI, 0.3-6.1) , for tafasitamab/lenalidomide and Pola-BR, respectively. A statistical comparison of DOR was not possible in each arm due to a low number of patients with tumor assessment data. The median progression-free survival (PFS) was 8.0 months (95% CI, 1.9-19.9) in the tafasitamab group vs 5.0 months (95% CI, 2.5-5.6) for Pola-BR (HR, 0.482; 95% CI, 0.217-1.073; P = .0689).
In the R2 comparison, the ORR was 63.6% (95% CI, 45.1-79.6) with tafasitamab plus lenalidomide compared with 30.3% (95% CI, 15.6-48.7) for R2 (P = .0130). The CR rates for each regimen, respectively, were 39.4% (22.9%-57.9%) and 15.2% (95% CI, 5.1-31.9). The median DOR was 34.8 months (95% CI, 3.6-34.8) with tafasitamab compared with 12.4 months (95% CI, 2.7-19.3) for R2. The median PFS was 5.9 months (95% CI, 3.6-36.7) vs 2.8 months (95% CI, 2.0-5.8) for tafasitamab/lenalidomide and R2, respectively (HR, 0.511; 95% CI, 0.281-0.927; P = .0272).
In the CAR T-cell comparison, the ORR was 59.5% (95% CI, 42.1-75.2) with the tafasitamab combination vs 75.7% (95% CI, 58.8%-88.2%) with the CAR T-cell therapy (P = .2140). The CR rates were 37.8% (95% CI, 22.5%-55.2%) and 43.2% (95% CI, 27.1-60.5%) and the median DOR was 26.1 months (95% CI, 4.4-NR) and 5.9 months (95% CI, 2.0-10.0), for the tafasitamab and CAR T-cell arms, respectively. The median PFS was 6.3 months (95% CI, 3.6-22.5) with tafasitamab/lenalidomide vs 4.0 months (95% CI, 3.1-12.8) with CAR T cells (HR, 0.612; 95% CI, 0.302-1.240; P = .1696).
Findings from the RE-MIND2 study were compared with real-world efficacy findings and those observed in published literature for each agent, to ensure they correlated well with existing data. Overall, there was a correlation between the median OS observed for each agent in RE-MIND2 and these data, Nowakowski noted.
“The RE-MIND2 study design used strict patient-level matching, which is very different from cross-study comparison of results. I believe this is one way we can evaluate and compare the results of the different regimens in practice,” he said. “Such studies will shed additional light on the sequence of therapies in these settings.”
Nowakowski GS, Yoon DH, Mondello P, et al. Tafasitamab plus lenalidomide versus Pola‑BR, R2, and CAR T: comparing outcomes from RE-MIND2, an observational, retrospective cohort study in relapsed/refractory diffuse large B-cell lymphoma. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 183.