Mosunetuzumab 1mg/1ml solution for infusion vials

Abstract Introduction Patients with follicular lymphoma (FL) receiving third-line or later (3L +) therapy have long survival, which can make estimating long-term overall survival (OS) from trial data challenging. The objective of this study was to estimate long-term OS for mosunetuzumab from the GO29781 trial (NCT02500407) using multiple real-world databases (RWDs) in a Bayesian framework. Methods Seven RWD sources for patients with FL receiving 3L + therapy and the expansion cohort in the GO29781 trial for mosunetuzumab were used. Hazard trends from the RWD sources were analyzed, and disease-wide pointwise OS and its corresponding uncertainty were estimated using Bayesian random-effects meta-analysis from the RWD sources. Pointwise OS obtained was used as an informative prior in Bayesian survival extrapolations to data from patients receiving mosunetuzumab. Results after adjusting for background mortality were compared to equivalent frequentist extrapolations using trial data only. Results Hazard patterns from RWD sources supported a constant or linearly decreasing hazard. Mean pointwise OS for patients with FL receiving 3L + therapy was estimated at 0.52 (95% credible interval, 0.29–0.85) at 8 years. Bayesian extrapolations for mosunetuzumab produced median survival estimates of 11.6 (6.7–20.7) years to 17.0 (6.4–22.7) years depending on the distribution used, reducing uncertainty by 20% to 46% relative to the frequentist estimation. Conclusion Multiple RWD sources can be synthesized to augment the credibility of data with short follow-up, long patient survival, and few events to effectively estimate long-term survival and reduce estimated uncertainty. This method can be applied to other indications with similar characteristics. Clinical Trial Registration Number and Date of Registration NCT02500407, July 16, 2015.

Abstract licence: CC BY-NC 4.0

Paolo Lopedote,1 Mazyar Shadman2,3 1Department of Medicine, St Elizabeth’s Medical Center, Boston, MA, USA; 2Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; 3Department of Medicine, University of Washington, Seattle, WA, USACorrespondence: Mazyar Shadman, Clinical Research Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave, Seattle, WA, 98109, USA, Tel +1 206-667-5467, Email mshadman@fredhutch.orgAbstract: Follicular lymphoma is the most common indolent non-Hodgkin’s lymphoma, and because of the incurable nature of this disorder, new therapies are constantly needed. The recently approved T-cell-dependent bispecific antibody mosunetuzumab showed promising results and manageable toxicities for patients with relapsed or refractory follicular lymphoma. Namely, as opposed to cellular immunotherapy options, this agent has the potential of being effective in patients with unfavorable features with a tolerable rate and severity of cytokine release syndrome, immune effector cell-associated neurotoxicity, and infectious complications. Given the recent withdrawal from the market of PI3K inhibitors and the practical challenges in utilizing with chimeric antigen receptor T-cells (CAR-T) for some patients, mosunetuzumab represents a “breath of fresh air” for both patients and hemato-oncologists. More data are required to better define the real potential of this molecule, either alone or in combination with other agents, including antibody drug conjugates, immunomodulators, and checkpoint inhibitors. Future studies will also shed light on the efficacy of mosunetuzumab compared with CAR-T, in well-designed registries or ideally in randomized controlled trials.Keywords: mosunetuzumab, follicular lymphoma, T-cell-dependent bispecific, bispecific antibody

Abstract licence: CC BY-NC 3.0