Research by Adam S. Kittai, MD, at the Icahn School of Medicine at Mount Sinai in New York, and colleagues has documented commercial anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy as a clinically effective treatment for patients with Richter transformation (RT). An international consortium of 12 centers collected data representing the largest cohort (n=69) of patients receiving commercial CAR-T. They published the findings from the retrospective study in the Journal of Clinical Oncology.
Patients were a median age of 64 and had received a median of four previous lines of therapy for chronic lymphocytic leukemia or RT. Most (84%) had received BTK inhibitor, BCL2 inhibitor therapy, or both. Patients received different CAR-T products: 64% received axicabtagene ciloleucel, 25% received tisagenlecleucel, 10% received lisocabtagene maraleucel (liso-cel), and one patient received brexucabtagene autoleucel.
Investigators documented an overall response rate of 63% and a complete response (CR) rate of 46%, the latter of which was similar to that of the pivotal trials in large B-cell lymphoma (LBCL). For patients achieving a CR, the median duration of response was 27.6 months (95% CI 14.5 to not reached), which Dr. Kittai emphasized is “fantastic for patients with RT.” Unfortunately, the median progression-free survival was 4.7 months (95% CI 2.0-6.9), lower than that documented in pivotal studies and real-world series for commercial CAR-T in standard LBCL.
The median overall survival (OS) was 8.5 months (95% CI 5.1-25.4), and the two-year OS was 38% (95% CI 26-50). The estimated rate of non-relapse mortality at 12 months was 13%, with infection being the cause of most non-relapse deaths. Thus, while a proportion of patients derived benefits from CAR-T therapy and achieved a CR, most patients either did not respond or achieved a partial response as the best response, progressed quickly, and died of disease. Because of this, the authors recommend that clinicians perform short interval follow-up scans in patients with partial response to detect either response evolution to CR or early progression.
Even though the mostly older patient population was heavily pretreated, CAR-T therapy was associated with manageable toxicity. Sixteen percent of patients experienced grade 3 or higher cytokine release syndrome, and 37% experienced immune effector cell-associated neurotoxicity syndrome.
“Patients with RT have poor outcomes,” Dr. Kittai said. “Any new treatment that shows any benefit should be looked at as a win for this patient population.” He explained that CAR-T, specifically liso-cel, is now approved for patients with RT, as it is approved for patients with diffuse LBCL arising from indolent lymphoma. The efficacy is noteworthy, he said, given that “these patients have few options, and this treatment led to durable responses in patients who attained a CR.”
“The main predictor of outcomes is how well controlled the disease is,” Dr. Kittai said, noting lactate dehydrogenase (LDH) was the main predictor of outcome. Delays in treatment can contribute to elevated LDH, progressive disease, and worse outcomes. Additionally, the study revealed that the more lines of treatment patients received, the worse their outcomes were.
“We should be thinking of CAR-T in earlier lines of therapy and even first-line therapy for these patients,” Dr. Kittai said. While there used to be a three- to four-week delay in obtaining CAR-T therapy, companies have ramped up their manufacturing capacity, and many oncology centers are expanding their ability to provide patients access to the therapy.
“All patients with RT should be seen by a physician familiar with RT,” Dr. Kittai said. “Access is essential to receiving this high level of care.”
The authors noted that because the study was retrospective in nature, not all data collected in prospective trials of CAR-T were available. For example, the study did not include data regarding patients for whom CAR-T was intended but not infused.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Kittai AS, Bond D, Huang Y, et al. Anti-CD19 chimeric antigen receptor T-cell therapy for Richter transformation: an international, multicenter, retrospective study. J Clin Oncol. 2024;42(17):2071-2079.
