CAR T-Cell Therapy for Richter’s Transformation

In this JCO Article Insights episode, Alexandra Rojek provides a summary on "Anti-CD19 Chimeric Antigen Receptor T-cell therapy for Richter’s Transformation: An International, Multicenter, Retrospective Study by Kittai, et al published in the Journal of Clinical Oncology March 29th, 2024. 

TRANSCRIPT

The guest on this podcast episode has no disclosures to declare.

Alexandra Rojek: Hello and welcome to JCO Article Insights. I'm your host, Alexandra Rojek, and today we will be discussing an original report published in the June 10th issue of JCO titled, “Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study,” by Kittai et al. This report addresses the real world efficacy of CAR T-cell therapy for patients with Richter transformation of CLL to large B cell lymphoma, which represents a high risk group of patients with an unmet need for novel and more effective therapeutic agents than are currently available. Richter's represents the transformation of chronic lymphocytic leukemia, or CLL, to an aggressive lymphoma, most often a large B cell lymphoma, most similar to diffuse large B cell lymphoma or DLBCL. Treatment for Richters is often modeled after treatment practices for DLBCL. However, there's no clear standard of care and outcomes for these patients lag behind those of large B cell lymphoma patients otherwise.

An important advance in recent years in the DLBCL field is the approval of anti CD19 CAR T-cell therapy in the second and third line settings. However, patients with Richter transformation were largely excluded from these pivotal trials. This study in JCO thus set out to address what the real world outcomes were for patients with Richters who were treated with CAR T-cell therapy across 12 centers internationally. The study included 69 patients across these twelve sites, with a median age of 63 years at diagnosis of Richters and a median of six years after initial CLL diagnosis. Included patients received a median of four prior lines of therapy for either CLL or Richters, with a median of two prior lines of therapy for Richters, although two patients had not received any prior therapy for their Richter transformation.

The most recent prior treatments included chemoimmunotherapy in 29% of patients, followed by BTK inhibitors in 19%, as well as combinations of BTK inhibitors and BCL2 inhibitors in 12%. 17% of patients had not received prior therapy for their CLL before their diagnosis with Richters, 58% of cases had known TP53 mutations at time of transformation, and 41% exhibited deletion 17p by FISH. Prior to receiving CAR T-cell therapy, 86% of patients required additional bridging therapy, most commonly with a BTK inhibitor or chemoimmunotherapy. A diverse set of commercial CAR T-cell products were represented in this study, with the majority of patients at 64% receiving axi-cel, 25% receiving tisa-cel, 10% receiving liso-cel, and one patient received brexu-cel in an investigational setting. Median time from apheresis to CAR T infusion was 34 days, and 59% of patients continued on a BTK inhibitor throughout CAR T-cell therapy.

When we move on to look at responses, 66 out of 69 patients were available for response. Three patients died related to adverse events after infusion and before response assessment, with the best overall response of complete response or CR in 46% of patients and partial response or PR in 17% for an overall response rate of 63%. With a median follow up time of 24 months, the median PFS in the study was 4.7 months and the median OS was 8.5 months. For those who achieved a CR, the median duration of response was an impressive 27 months, and for those achieving PR, the median duration of response was only two months. The two year PFS rate was thus 28%, and the two year OS