Treatment of Diffuse Large B-cell Lymphoma Progressing or Relapsing after Chimeric Antigen Receptor T-cell Therapy

There is no established standard treatment for diffuse large B-cell lymphoma (DLBCL) progressing or relapsing after chimeric antigen receptor T-cell therapy (CAR T-cell). While enrollment in clinical trials is ideal, unfortunately, many are not eligible to participate. Various treatment modalities exist with different efficacies. To assess the efficacy of various treatment modalities, including allogeneic hematopoietic cell transplantation (allo-HCT), Bruton's tyrosine kinase inhibitors, bispecifics, checkpoint inhibitors, chemotherapy/chemoimmunotherapy, lenalidomide-based, polatuzumab-based, radiation-based, and tafasitamab or loncastuximab-based therapy for the management of DLBCL, we performed a systematic review (SR) and meta-analysis (MA). Any prospective or retrospective study assessing the role of any of the above-mentioned treatment regimens in patients with progressing or relapsing after CAR T-cell, enrolling a minimum of 10 patients, was eligible for inclusion. A comprehensive search of PubMed and EMBASE was performed on August 14, 2024. The methodological quality of the included studies was graded using the modified Newcastle-Ottawa scale. We pooled untransformed proportions using a random-effects model to pool data from eligible studies with similar definitions relating to treated subjects, design, and outcomes. Results are reported as rates with their corresponding 95% confidence intervals. Of the 951 references identified in the initial search, 24 met the inclusion criteria. The pooled objective response rates with allo-HCT, polatuzumab-based regimens, and bispecifics were 59%, 57%, and 51%, respectively. The highest pooled complete remission rates were with allo-HCT (38%), followed by bispecifics (33%) and polatuzumab-based regimens (29%). The pooled overall survival rate was highest with allo-HCT recipients (59%), which is partly explained by the lower pooled relapse rate (27%). The results from this SR/MA aimed at providing the totality of evidence pertaining to the efficacy (or lack thereof) of various available therapies considered in relapsed and/or refractory DLBCL after CAR T-cell therapy show that treatment choice is a complex process that must consider the patient's performance status and disease-related characteristics, whether localized or systemic, and history of prior therapies, among others.