Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma

Francesc Bosch; John Kuruvilla; Theodoros P Vassilakopoulos; Danilo Di Maio; Michael C Wei; Marie-Helene Blanchet Zumofen; Loretta J Nastoupil

doi:10.1016/j.clml.2023.09.007

Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma

Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):105-121. doi: 10.1016/j.clml.2023.09.007. Epub 2023 Sep 28.

Authors

Francesc Bosch¹, John Kuruvilla², Theodoros P Vassilakopoulos³, Danilo Di Maio⁴, Michael C Wei⁵, Marie-Helene Blanchet Zumofen⁴, Loretta J Nastoupil⁶

Affiliations

¹ Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: fbosch@vhebron.net.
² Princess Margaret Cancer Centre, Toronto, ON, Canada.
³ Department of Haematology and Bone Marrow Transplantation, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁴ F. Hoffmann-La Roche, Basel, Switzerland.
⁵ Genentech, South San Francisco, CA.
⁶ The University of Texas MD Anderson Cancer Center, Houston, TX.

PMID: 37981564
DOI: 10.1016/j.clml.2023.09.007

Abstract

Background: No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting.

Methods: A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations. Imbalances in patient characteristics between NCT02500407 and studies featuring aggregate or patient-level data availability were accounted for using matching-adjusted indirect comparison (MAIC) and propensity score-based methodologies, respectively.

Results: ZUMA-5, ELARA, DELTA, DYNAMO, UNITY-NHL, AUGMENT and NCT01897571 passed the MAIC feasibility assessment. Patient-level data were available from GADOLIN, CONTRALTO and NCT02257567. MAIC results generally favored mosunetuzumab over tazemetostat in EHZ2wild-type patients for all outcomes and over PI3K inhibitors for complete response (CR), objective response rate (ORR), discontinuations due to adverse events and progression-free survival (PFS) with umbralisib. MAICs favored CART therapies for PFS and, to a lesser extent, ORR and CR. Comparisons with anti-CD20 antibody-based regimens yielded mixed results.

Conclusions: ITCs suggest that mosunetuzumab may lead to superior outcomes over tazemetostat (in EHZ2wild-type patients) and PI3K inhibitors and may be a promising alternative to re-challenging with a different anti-CD20 regimen in patients who relapse after ≥2 prior anti-CD20 lines. Although preliminary results somewhat favored CART therapies, limitations and uncertainties remain because of intrinsic differences in study design. Mosunetuzumab could thus be a promising treatment option for patients with RR FL after ≥2 prior therapies.

Keywords: Anti-CD20 antibodies; Bispecific antibody; CART therapy; Comparative efficacy; Non-Hodgkin lymphoma.

Publication types

Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Bispecific* / therapeutic use
Antineoplastic Agents* / therapeutic use
Benzamides*
Biphenyl Compounds*
Humans
Lymphoma, Follicular* / drug therapy
Morpholines*
Neoplasm Recurrence, Local / drug therapy
Phosphatidylinositol 3-Kinases
Pyridones*

Substances

tazemetostat
Phosphatidylinositol 3-Kinases
Antineoplastic Agents
Antibodies, Bispecific
Benzamides
Biphenyl Compounds
Morpholines
Pyridones

Associated data

ClinicalTrials.gov/NCT02257567
ClinicalTrials.gov/NCT02500407
ClinicalTrials.gov/NCT01897571