Key Subgroup Analyses Supports Tafasitamab Plus Lenalidomide for High-Risk R/R DLBCL

Grzegorz S. Nowakowski, MD

Treatment with tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) demonstrated trends toward improved overall survival (OS) vs systemic regimens across key subgroups of patients with high-risk relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for transplant, according to findings from an observational, retrospective analysis of the cohort RE-MIND2 study (NCT04697160), presented at the 2022 ASCO Annual Meeting.¹

Investigators leveraged efficacy outcomes of patients who received tafasitamab plus lenalidomide in the phase 2 L-MIND trial (NCT02399085), in which treatment with the combination elicited favorable outcomes for patients not eligible for autologous stem cell transplant (ASCT).² Matched analysis sets were created for using an estimated propensity score–based method to compare outcomes of tafasitamab plus lenalidomide with patients treated with other systemic therapies for DLBCL pooled in a single cohort and cohorts comprising patients treated with common regimens.

Patients from L-MIND were closely matched with patients from 4 RE-MIND2 cohorts using estimated propensity score based 1:1 nearest neighbor matching balanced for up to 9 baseline covariates according to clinical relevance and other available patient records.

Patients in subgroups were compared for OS outcomes based on the number of extranodal sites and presence or absence of elevated lactate dehydrogenase (LDH) level.

“The hazard ratio for OS suggests a trend toward favoring tafasitamab plus lenalidomide in each matched analysis set overall, and in most patient subgroups,” said lead investigator Grzegorz S. Nowakowski, MD, of the Division of Hematology at the Mayo Clinic in Rochester, Minnesota.

“In each subgroup examined, there was a trend favoring enhanced OS with tafasitamab plus lenalidomide when compared with systemic therapies pooled, rituximab [Rituxan] plus lenalidomide [Revlimid; R2], and polatuzumab [Polivy] plus bendamustine and rituximab [pola-BR].”¹

For the tafasitamab plus lenalidomide vs systemic therapies pooled matched cohort comparison, the median OS was as follows:

• 34.1 months vs 11.6 months, respectively, in the overall cohort (HR, 0.553; 95% CI, 0.358-0.855; P = .0068)
• Not reached (NR) vs 14.5 months in those with 0 or 1 extranodal sites (HR, 0.476; 95% CI, 0.27-0.85)
• 14.8 vs 9.4 months in patients with 2 or more extranodal sites (HR, 0.803; 95 CI%, 0.40-1.61)
• NR vs 21.7 months in patients without elevated LDH (HR, 0.448; 95% CI, 0.21-0.96)
• 18.3 vs 8.3 months in those with elevated LDH (HR, 0.627; 95% CI, 0.37-1.07)

For the tafasitamab plus lenalidomide vs pola-BR matched cohort comparison, the median OS was as follows:

1. 20.1 months vs 7.2 months, respectively, in the overall cohort (HR, 0.441; 95% CI, 0.203-0.956; P = .0340)
2. 24.8 vs 8.5 months in those with 0 or 1 extranodal sites (HR, 0.573; 95% CI, 0.20-1.65)
3. 7.6 vs 6.1 months in patients with 2 or more extranodal sites (HR, 0.524; 95% CI, 0.14-2.02)
4. NR vs 8.5 months in patients without elevated LDH (HR, 0.388; 95% CI, 0.08-1.79)
5. 11.6 vs 6.7 months in those with elevated LDH (HR, 0.585; 95% CI, 0.24-1.41)

For the tafasitamab plus lenalidomide vs R2 matched cohort comparison, the median OS was:

1. 24.6 months vs 7.4 months, respectively, in the overall cohort (HR, 0.435; 95% CI, 0.224-0.847; P = .0122)
2. 31.6 months vs 9.5 months in those with 0 or 1 extranodal sites (HR, 0.491; 95% CI, 0.19-1.28)
3. 24.6 months vs 6.2 months in patients with 2 or more extranodal sites (HR, 0.478; 95% CI, 0.17-1.34)
4. NS vs NR in patients without elevated LDH (HR, 0.664; 95% CI, 0.15-3.01)
5. 13.8 months vs 5.2 months in those with elevated LDH (HR, 0.420; 95% CI, 0.19-0.95)

For the tafasitamab plus lenalidomide vs CD19-directed CAR-T cell therapy matched cohort comparison, the median OS was:

1. 22.5 months vs 15.0 months, respectively, in the overall cohort (HR, 0.953; 95% CI, 0.475-1.913; P = .8929)
2. 31.6 months vs 27.3 months in those with 0 or 1 extranodal sites (HR, 0.717; 95% CI, 0.28-1.85)
3. 7.6 months vs 14.6 months in patients with 2 or more extranodal sites (HR, 1.459; 95% CI, 0.52-4.11)
4. NR vs 14.6 months in patients without elevated LDH (HR, 0.371; 95% CI, 0.12-1.15)
5. 8.6 vs 15.9 months in those with elevated LDH (HR, 1.663; 95% CI, 0.0.66-4.19)

“The observed trend of shorter OS duration of CAR-T cells versus tafasitamab plus lenalidomide in high-risk patients warrants further investigation,” Nowakowski said. “We note that analyses between tafasitamb and comparator therapies are not powered for statistical comparison. Small sample size resulted in wide confidence intervals; therefore, those results must be interpreted with caution.”

The differences in cohort sizes reflects availability of baseline covariate data in hospital databases for therapies of interest, Nowakowski said, adding that despite small sample sizes, “these results may aid in contextualizing therapy options for treating patients with R/R DBCL.”

References

1. Nowakowski GS, Yoon DH, Joffe E, et al. Subgroup analysis in RE-MIND2, an observational, retrospective cohort study of tafasitamab plus lenalidomide versus systemic therapies in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). J Clin Oncol. 2022;40(suppl 16):7560. doi:10.1200/JCO.2022.40.17_suppl.7560.
2. Salles G, Duell J, Barca EG, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4