Introduction: Tafasitamab plus lenalidomide (TAFA + LEN) received accelerated US Food and Drug Administration approval and conditional European Medicines Agency approval for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for autologous stem cell transplant. This study investigates the relative efficacy of TAFA + LEN versus comparator treatments.
Methods: Matching-adjusted indirect comparisons (MAICs) of TAFA + LEN were performed using data from L-MIND, and comparator studies assessing rituximab-based combination therapies, including polatuzumab vedotin + bendamustine + rituximab (POLA + BR) bendamustine + rituximab (BR), and gemcitabine + oxaliplatin + rituximab (R-GEMOX) to provide relative efficacy estimates for overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and complete response rate (CRR). Patient-level data from L-MIND were weighted to match reported distributions of clinically validated prognostic factors and effect modifiers in comparator trials. MAIC results versus multiple BR studies were pooled using meta-analysis.
Results: MAICs were feasible versus POLA + BR and BR. Compared to POLA + BR, TAFA + LEN was associated with significantly longer DOR [hazard ratio (HR) 0.34 (95% CI 0.12, 0.98); p = 0.045]. Due to concerns about the proportional hazard assumption for OS and PFS, separate HRs were estimated before and after 4 months of follow-up. OS after 4 months, was significantly greater for TAFA + LEN versus POLA + BR [HR 0.41 (95% CI 0.19, 0.90); p = 0.026]. Compared with BR, TAFA + LEN was associated with significantly improved OS [GO29365 comparator trial: HR 0.39 (95% CI 0.18, 0.82); p = 0.014], PFS (pooled data: HR 0.39 (95% CI 0.29, 0.53); p < 0.001], DOR [pooled data: HR 0.35 (95% CI 0.25, 0.50); p < 0.001], and CRR [pooled data: odds ratio 2.43 (95% CI 1.33, 4.41); p = 0.004].
Conclusion: In MAIC analyses, treatment with TAFA + LEN for R/R DLBCL provided better OS and PFS outcomes than standard treatment regimens. Validation from large, randomized, phase 3 clinical trials is required to confirm these results.
Keywords: Diffuse large B-cell lymphoma; Indirect treatment comparison; Lenalidomide; Matching-adjusted indirect comparison; Relapsed/refractory; Rituximab; Tafasitamab.
Tafasitamab in combination with lenalidomide has been recently approved for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma. There are no clinical trials to directly compare the outcomes of tafasitamab + lenalidomide against other treatments for diffuse large B-cell lymphoma. Matching-adjusted indirect comparisons allow an estimate of the relative efficacy of treatments to be derived in the absence of head-to-head comparisons from clinical trials. Matching-adjusted indirect comparisons analyses utilizing data from previously published clinical trials were conducted to compare the combination of tafasitamab + lenalidomide against 3 standard treatments for relapsed or refractory diffuse large B-cell lymphoma: polatuzumab vedotin + bendamustine + rituximab, bendamustine + rituximab, and rituximab + gemcitabine + oxaliplatin. Compared to those treated with polatuzumab vedotin + bendamustine + rituximab, patients treated with TAFA + LEN maintained their response to treatment for longer and are more likely to experience long-term survival. When compared to those treated with bendamustine + rituximab, patients treated with TAFA + LEN had increased survival, a higher level of response, and maintained their response to treatment for longer. Overall, the findings suggest that treatment with TAFA + LEN for R/R DLBCL is likely to result in significantly better outcomes compared with standard rituximab-based treatments.
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