Patients in their 80s or older with B-cell lymphomas are able to receive chimeric antigen receptor (CAR) T-cell therapy safely, results of a multicenter retrospective study published in Bone Marrow Transplantation showed. These patients are usually not eligible for clinical trials of CAR T-cell products due to their age.
“The study demonstrated that CAR T-cell therapy is feasible in patients 80 and older,” stated Deepa Jagadeesh, MD, Staff Physician in the Hematology and Medical Oncology Department at Cleveland Clinic Cancer Institute, and one of the study authors. “The 1-year progression-free survival was close to 50%, which is very encouraging. This is a reminder to physicians not to use age as a single exclusion criterion. CAR T-cell therapy can produce effective, long-term remission in many patients in their 80s.”
Study Methods and Rationale
Older patients are typically not represented in pivotal clinical trials for CAR T-cell therapies for hematologic malignancies, even though approximately one-third are diagnosed when they are in their 70s or above. Clinical trials tend to prefer including more stable, healthy patients where possible so that they can more easily determine what effects are the result of the drug rather than from other comorbidities.
Patients 80 or above with refractory B-cell lymphoma are often treated with chemotherapy or bispecific antibodies rather than being offered CAR T-cell therapy, which is potentially curative.
“In most cases, older patients were excluded from CAR T-cell therapy trials due to medical comorbidities or suboptimal functional status,” Dr. Jagadeesh said. “We wanted to understand how these patients fared on this emerging treatment.”
The researchers gathered patient records for 88 patients across 16 cancer centers. These patients were all 80 years or older (median age, 82) with relapsed or refractory B-cell lymphoma that was treated with a CD19-directed CAR T-cell therapy between January 2018 and December 2023. The majority of patients had diffuse large B-cell lymphoma (68.2%) and received axicabtagene ciloleucel (46.6%).
Key Study Findings
The analysis found that the non-relapse mortality rate at 1 year was 11.6%, the relapse rate at 1 year was 40.8%, the 1-year progression-free survival rate was 57.6%, and the 1-year overall survival rate was 61.2% for patients with diffuse large B-cell lymphoma or transformed follicular lymphoma. Among patients with mantle cell lymphoma, the 1-year progression-free survival rate was 45%. Over 70% of all evaluable patients achieved a complete response and 17.9% achieved a partial response.
Cytokine-release syndrome (CRS) of any grade was observed in 77.3% of all patients and was grade 3 or 4 in 7.4%. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 58% of all patients and was grade 3 or 4 in 31.4%. Some cases of CRS or ICANS recurred.
About one-quarter of patients were re-admitted to the hospital in the first 100 days after CAR T-cell therapy administration due to CRS, ICANS, failure to thrive, atrial fibrillation, or infection.
The study authors emphasized that frailty assessment tools should be incorporated into care for these older patients receiving CAR T-cell therapy; that multidisciplinary care can help to provide these patients with additional supportive measured; and that CAR T-cell therapy should be started as soon as possible for these patients.
“There has been an explosion of new treatments for diffuse large B-cell lymphoma,” Dr. Jagadeesh said. “We need to be considering each of these at the correct time, and ensure all patients who are eligible have access to appropriate treatment.”
Disclosure: For full disclosures of the study authors, visit nature.com.
