Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial.

Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody-drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8-69.0) and 45.9% (45/98; 95% CI: 35.8-56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5-not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2-18.7). Median overall survival was 23.3 months (95% CI: 14.8-NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 .

COVID-19 Vaccine-Related Local FDG Uptake.

ABSTRACT: We present a case of increased FDG uptake in the lymph nodes after COVID-19 vaccine administration. Restaging PET/CT scan of a 70-year-old woman with a history of multiple relapsed Hodgkin lymphoma showed muscle activity in the left upper arm laterally, which is in the deep musculature of the left deltoid muscle. There was also increased activity in several normal-sized left axillary nodes as well. On further review of the patient's history, she had received her second shot of the Pfizer-BioNTech COVID-19 vaccine approximately 2 days before the restaging PET/CT scan.

Addressing Recent Failures in Immuno-Oncology Trials to Guide Novel Immunotherapeutic Treatment Strategies.

The incorporation of checkpoint inhibitors into the treatment armamentarium of oncologic therapeutics has revolutionized the course of disease in many cancers. This has spurred the evaluation of other novel immunotherapy agents in clinical trials with varying levels of success. This review explores possible explanations for differences in efficacy in clinical outcomes among currently US FDA-approved immunotherapy agents, lessons learned from clinical trial failures of investigational immunotherapies, and methods to improve success in the future. An inherent challenge of early phase immunotherapy trials is identifying the maximum tolerated dose and improving understanding of the pharmacokinetics/pharmacodynamics of immunotherapies as they exert their effects indirectly via T cells rather than directly via dose-dependent cytotoxic activity. The wide heterogeneity of the immune system among patients and within an individual patient over time largely affects the results of optimal dose- and toxicity-finding studies as well as the effectiveness of immunotherapy. Therefore, optimization of phase I/II study design is crucial for clinical trial success. These differences may also help elucidate the lack of immunotherapy benefit in certain disease subtypes despite the presence of specific biomarkers. Broader investigation of the tumor microenvironment and its dynamic nature can help in the identification of alternative pathways for targeted therapies, mechanisms of immunotherapy resistance, and more correlative biomarkers. Finally, manipulation of the tumor microenvironment via a single agonist or antagonist may be inadequate, so combination therapies and sequencing of agents must be further assessed while balancing cumulative toxicity risk.