Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02094-5.

Cost‐effectiveness analysis of transplant‐ineligible relapsed or refractory diffuse large B‐cell lymphoma treatment options—Experience of the efficiency frontier approach

“…Although considering a longer time horizon over 5 years, Tafa‐L was found to demonstrate better survival outcomes than pola‐BR, whereby it incurred higher costs 58 . In a matching‐adjusted indirect comparison (MAIC), the improved survival outcomes of Tafa‐L compared to pola‐BR and BR were confirmed 59 . Furthermore, pola‐BR was found to be more cost‐effective than BR, predominantly driven by higher survival outcomes 60 .…”

“…58 In a matching-adjusted indirect comparison (MAIC), the improved survival outcomes of Tafa-L compared to pola-BR and BR were confirmed. 59 Furthermore, pola-BR was found to be more cost-effective than BR, predominantly driven by higher survival outcomes. 60 Various MAIC studies compared CAR-T therapies, indicating higher efficacy results for liso-cel and axicel than for tisa-cel.…”

Real-world outcomes of the efficacy and safety of polatuzumab vedotin combination regimen in patients with relapsed/refractory diffuse large B cell lymphoma

“…However, direct comparisons between these various agents have yet to be conducted. This emphasizes the ongoing need for research to establish the most effective treatment strategies for these patients [24].…”

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy

“…Matching-adjusted indirect comparisons of tafasitamab plus lenalidomide were performed using data from the L-MIND study and comparator studies assessing rituximab-based combination therapies, including PolaBR, showing longer duration of response and higher median OS but not differences in response rates or PFS were found. 20 Recognizing that response rates and PFS are not dissimilar to the ones obtained with other drugs, it is, however, important to underline for this reason that PolaBR has to find its place in the therapeutic algorithm of DLBCL. The challenge is to understand the right sequence of the available options, or rather if the same drugs sequence can be identified for all DLBCL patients or each patient can benefit from a personalized sequence.…”