CAR T-Cell therapy for the management of mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma (NHL) of mature B-cells characterized by translocation, which is typically due to excess expression of Cyclin D1. Although with the progress in our knowledge of the causes for MCL and available treatments for MCL, this cancer is still incurable. Age, male gender, rapid advancement, significant nodal involvement, elevated serum lactate dehydrogenase level, and prognostic indications including increased expression of Ki-67 and presence of TP53 mutation, are symbols of poor outcome. Advanced immunotherapy using chimeric antigen receptor (CAR)-T cells is advantageous for patients suffering from B-cell malignancies and MCL. Targeting B-cell antigens on the cell surface is a feasible approach in re-occurring (R/R) MCL because of significant responses obtained in other B-cell cancers. USFDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19), a novel CAR T-cell therapy to be used in patients with MCL who have not responded to previous treatments or have relapsed. The FDA approved this new treatment depending on the outcomes of the ZUMA-2 clinical trial. Serious adverse reactions, moderate anti-tumor activity, allergen withdrawal, antigen escape, limited tumor infiltration, and trafficking are major barriers to successful CAR T-cell therapy. This review is a brief synopsis of the development of CAR T-cell therapy for MCL.

Clinical and Genetic Analysis of Li-Fraumeni Syndrome with Novel TP53 Mutations

“…Megyesfalvi Z et al [30] found widespread inactivation of the TP53 gene in small cell lung cancer, suggesting potential e cacy of immunotherapy in this context. Chen et al [31] reported the rst case of CAR-T cell therapy in an LFS patient with hematological malignancy, suggesting that CAR-T cell therapy may be an alternative option compared to traditional chemotherapy and allogeneic hematopoietic stem cell transplantation. In our research, the CPS of PD-L1 in the proband 1 was 70%, and the patient received radical resection, postoperative chemotherapy combination with immunotherapy.…”

Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor

“…In an adjusted comparison using inverse probability weighting between ZUMA-2 and SCHOLAR-2, brexu-cel was associated with improved OS compared to non-CAR T cell standard of care (HR 0.38, 95% CI 0.23–0.61) [ 34 ]. Efficacy of CAR T cell therapy should be considered alongside potential class-specific toxicities, such as immunologic effector cell-associated cytokine release syndrome and neurotoxicity, among other potential constraints to successful CAR T cell therapy [ 35 ]. To our knowledge, pirtobrutinib has yet to be evaluated in the real-world setting; however, the therapy is currently undergoing phase 3 evaluation in the cBTKi-naive setting of MCL, with comparison to ibrutinib, acalabrutinib, or zanubrutinib (BRUIN MCL-321 trial; NCT04662255).…”

Survival Outcomes of Patients with Mantle Cell Lymphoma: A Retrospective, 15-Year, Real-Life Study

“…In a retrospective study across 15 international sites, in which 114 patients were enrolled, median OS after ibrutinib failure was only 2.9 months [ 26 ]. In this setting, promising results were recently obtained by chimeric antigen receptor (CAR) T-cells [ 27 , 28 ]. Brexucabtagene autoleucel is a CD19-directed CAR T-cell therapy approved for R/R MCL after two previous regimens; 189 cases who underwent leukapheresis were enrolled in a real-life study.…”

“…Brexucabtagene autoleucel is a CD19-directed CAR T-cell therapy approved for R/R MCL after two previous regimens; 189 cases who underwent leukapheresis were enrolled in a real-life study. ORR and CR were 90% and 82%, respectively, with an estimated 12-month PFS of 59% after a median follow-up of 14.3 months [ 27 , 28 ]. However, this approach is not consistently feasible, due to restrictive eligibility criteria, progressive disease (PD), or death while waiting for manufacturing [ 27 , 28 ].…”

“…ORR and CR were 90% and 82%, respectively, with an estimated 12-month PFS of 59% after a median follow-up of 14.3 months [ 27 , 28 ]. However, this approach is not consistently feasible, due to restrictive eligibility criteria, progressive disease (PD), or death while waiting for manufacturing [ 27 , 28 ]. Furthermore, major treatment toxicities of CAR T-cell therapy include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, prolonged cytopenia, and infections [ 27 , 28 ].…”