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

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. 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. ZUMA-5, ELARA, DELTA, DYNAMO, UNITY-NHL, AUGMENT, NCT01897571 passed the MAIC feasibility assessment. Patient-level data were available from GADOLIN, CONTRALTO and NCT02257567. MAIC results generally favored mosunetuzumab over tazemetostat in EHZ2-wild-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. ITCs suggest that mosunetuzumab may lead to superior outcomes over tazemetostat (in EHZ2-wild-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. ITCs were conducted to compare mosunetuzumab with other ≥3L treatments for relapsed/refractory follicular lymphoma. The results suggested that mosunetuzumab is superior to tazemetostat (in patients without EZH2 mutations) and PI3K inhibitors. For anti-CD20 mAb therapies, outcomes varied depending on the efficacy endpoint. Results versus CART therapies varied depending on the technology, although mosunetuzumab's accessibility and safety should also be considered.