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.

• Authors: Raul Cordoba, Thibaud Prawitz, Tracy Westley, Anuj Sharma, Sumeet Ambarkhane, Venediktos Kapetanakis, Lorenzo Sabatelli
• Journal: Advances in therapy (Adv Ther) Vol. 39 Issue 6 Pg. 2668-2687 (06 2022) ISSN: 1865-8652 [Electronic] United States
• PMID: 35403948 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. Incyte Corporation.

Chemical References

• Antibodies, Monoclonal, Humanized
• Rituximab
• Bendamustine Hydrochloride
• Lenalidomide
• tafasitamab

Topics

• Adult
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bendamustine Hydrochloride (therapeutic use)
• Humans
• Lenalidomide (therapeutic use)
• Lymphoma, Large B-Cell, Diffuse (drug therapy)
• Rituximab (therapeutic use)
• Treatment Outcome