Page 163 - Haematologica Vol. 109 - July 2024

ARTICLE - Non-Hodgkin Lymphoma
Matching-adjusted indirect comparison from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence (LEO CReWE) study to a clinical trial of mosunetuzumab in relapsed or refractory follicular lymphoma
Matthew J. Maurer,1,2 Carla Casulo,3 Melissa C. Larson,1 Thomas M. Habermann,2 Izidore S. Lossos,4 Yucai Wang,2 Loretta J. Nastoupil,5 Christopher Strouse,6 Dai Chihara,5 Peter Martin,7 Jonathon B. Cohen,8 Brad S. Kahl,9 W. Richard Burack,3 Jean L. Koff,8 Yong Mun,10 Anthony Masaquel,10 Mei Wu,10 Michael C. Wei,10 Ashwini Shewade,10 Jia Li,10 James R. Cerhan,1 Brian K. Link6 and Christopher R. Flowers5
1Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN; 2Division of Hematology, Mayo Clinic, Rochester, MN; 3Department of Medicine, Wilmot Cancer Institute, University of Rochester, Rochester, NY; 4Department of Medicine, Comprehensive Sylvester Cancer Center, University of Miami, Miami, FL; 5University of Texas, MD Anderson Cancer Center, Houston, TX; 6Department of Medicine, University of Iowa, Iowa City, IA; 7Department of Medicine, Weill Cornell Medical College, New York, NY; 8Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA; 9Department of Medicine, Washington University in St Louis, St Louis, MO and 10Genentech, Inc., South San Francisco, CA, USA
Abstract
Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for R/R FL can provide some context for interpretation of single-arm trials. We compared the results from the mosunetuzumab trial to outcomes from a cohort of patients with R/R FL from the LEO Consortium for Real World Evidence (LEO CReWE). We applied clinical trial eligibility criteria to the LEO CReWE cohort and utilized match- ing-adjusted indirect comparison weighting to balance the clinical characteristics of the LEO CReWE cohort with those from the mosunetuzumab trial. ORR (73%, 95% CI: 65-80%) and CR rates (53%, 95% CI: 45-61%) observed in the weighted LEO CReWE cohort were lower than those reported on the mosunetuzumab trial (ORR=80%, 95% CI: 70-88%; CR=60%, 95% CI: 49-70%, respectively). PFS at 12 months was similar in the weighted LEO CReWE (60%, 95% CI: 51-69%) and the mosunetu- zumab (58%, 95% CI: 47-68%) trial. Sensitivity analyses examining the impact of matching variables, selection of line of therapy, and application of eligibility criteria provide context for best practices in this setting.
Introduction
Follicular lymphoma (FL) is a highly heterogeneous dis- ease often characterized as indolent in behavior requiring intermittent systemic therapy over time.1 Although most patients with FL will experience a life expectancy com-
parable to that of the general population, a subset will have early disease-related mortality, often preceded by early relapse following initial immunochemotherapy (IC), refractoriness to alkylator therapies, or transformation to aggressive lymphoma.2 Patients with relapsed or refractory (R/R) FL have several therapeutic options available without
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Correspondence: M.J. Maurer maurer.matthew@mayo.edu
Received: Accepted: Early view:
June 14, 2023. November 17, 2023. November 30, 2023.
https://doi.org/10.3324/haematol.2023.283737
©2024 Ferrata Storti Foundation Published under a CC BY-NC license