Polatuzumab vedotin 140mg powder for solution for infusion vials

IntroductionDespite recent approvals of new treatments, relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains challenging to treat, with limited durable responses and a high proportion of patients relapsing after two or more lines of therapy. Loncastuximab tesirine (Lonca) is a highly potent CD19-targeted antibody drug conjugate with convenient dosing for patients with third-line R/R DLBCL.MethodsIn the absence of head-to-head trials, unanchored matching-adjusted indirect comparisons (MAICs) were conducted to compare the relative efficacy and safety of Lonca with polatuzumab vedotin + bendamustine and rituximab (Pola + BR).ResultsFour studies included in the MAICs were identified via systematic review and hand-searching. Lonca (LOTIS-2) was compared with three comparator studies for Pola + BR (GO29365 extension study, COTA database, Dal et al. 2023). Overall, there was no evidence of a difference in overall response and complete response (CR) rates. Despite Pola + BR demonstrating a higher CR rate in the GO29365 extension study, this did not translate into significant improvements in progression-free or overall survival. Survival analyses indicated similar efficacy between treatments across studies, with most comparisons/meta-analyses showing no statistically significant differences. Lonca had significantly lower odds of Grade 3-4 infections, any serious adverse event (SAE), and specific SAEs including febrile neutropenia, pneumonia and pyrexia. Of the safety endpoints analyzed, none indicated significant differences in favor of Pola + BR.ConclusionThese results suggest no evidence of a difference in efficacy between the two treatments and potentially more favorable safety profile for Lonca compared with Pola + BR in patients with R/R DLBCL after two or more lines of treatment.

Abstract licence: CC BY-NC

Background Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma subtype with a significant relapse rate and poor prognosis in relapsed/refractory (R/R) patients. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) has demonstrated promising efficacy and safety as salvage therapy for R/R DLBCL. This systematic review protocol aims to comprehensively evaluate the efficacy of Pola-BR for the treatment of R/R DLBCL by synthesizing data from relevant randomized controlled trials. Methods This protocol details the eligibility criteria, search strategy, study selection, data extraction, and analysis methods for the systematic review. Randomized controlled trials comparing Pola-BR with other interventions for R/R DLBCL will be included. The primary endpoint is overall survival, with secondary endpoints being progression-free survival and incidence of adverse events. A comprehensive search will be conducted across databases such as Medline/PubMed, Cochrane Library, Web of Science, Scopus, EMBASE, ProQuest, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov from the January 2000 to April 2024. To assess the potential risk of bias, the Cochrane Risk of Bias 1 tool will be used. Data synthesis will utilize fixed-effect or random-effects models, and subgroup and meta-regression analyses will examine heterogeneity. Additionally, publication bias and sensitivity analyses will be performed, and the GRADE approach will be applied to assess the certainty of the evidence. Conclusion This systematic review and meta-analysis protocol provides a rigorous framework for evaluating the efficacy of Pola-BR in the treatment of R/R DLBCL. The results will inform clinical decision-making and guideline development, addressing the unmet need for effective and tolerable treatments for this challenging patient population. Potential limitations and biases will be acknowledged, and future research directions will be discussed.

Abstract licence: CC BY 4.0

Polatuzumab vedotin (polatuzumab vedotin-piiq; Polivy™) is an antibody-drug conjugate comprising a monoclonal antibody against CD79b (a B cell receptor component) covalently conjugated to the anti-mitotic cytotoxic agent monomethyl auristatin (MMAE) via a cleavable linker. After binding to CD79b on the B-cell surface, polatuzumab vedotin is internalized and the linker is cleaved, releasing MMAE into the cell, where it inhibits division and induces apoptosis. Polatuzumab vedotin is being developed by Genentech (a subsidiary of Roche) for the treatment of haematological malignancies. In June 2019, the US FDA granted accelerated approval to polatuzumab vedotin, in combination with bendamustine plus rituximab, for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies. Use of the compound in combination with bendamustine plus rituximab is also under regulatory review for relapsed/refractory DLBCL in the EU and is in ongoing phase 1b/2 development in this setting or relapsed/refractory follicular lymphoma (FL) in several countries. Various other polatuzumab vedotin combination therapy regimens are also in phase 1b/2 development for relapsed/refractory non-Hodgkin lymphoma (NHL) [including DLBCL and FL] or in phase 2 or 3 development for previously untreated DLBCL, while polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan. This article summarizes the milestones in the development of polatuzumab vedotin leading to this first approval for its use in combination with bendamustine plus rituximab for relapsed/refractory DLBCL.

Abstract licence: CC BY-NC 4.0