CAR-T effective, safe for certain patients with central nervous system-involved lymphoma
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SALT LAKE CITY — Chimeric antigen receptor T-cell therapy appeared effective for patients with primary or secondary central nervous system large B-cell lymphoma, according to study results.
The findings — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR — showed no increased risk for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS) among these patients.
“Based on these results, patients with primary or secondary CNS lymphoma should be included in future CAR T-cell therapy clinical trials,” Muhammad Husnain, MD, assistant professor of medicine in the division of hematology and oncology at University of Arizona Cancer Center, told Healio.
Background and methods
Patients with large B-cell lymphoma who relapse after initial chemotherapy typically experience poor outcomes.
CAR T-cell therapy is the best treatment option for these patients, Husnain said.
Three CAR-T products are approved for relapsed or refractory large B-cell lymphoma in the United States.
However, patients with primary or secondary CNS lymphoma have been excluded from CAR-T clinical trials due to potential life-threatening toxicities, such as ICANS and CRS.
Some retrospective and prospective studies have examined use of CAR T-cell therapy in real-world settings for patients with large B-cell lymphoma who have CNS involvement.
Husnain and colleagues conducted a systematic review and meta-analysis of published literature to evaluate the efficacy and safety of CAR T-cell therapy for patients with primary or secondary CNS lymphoma. They identified 17 studies that met inclusion criteria.
These studies — six case reports, plus 11 prospective or retrospective analyses and institutional observational studies — included a combined 113 patients (47.6% male). The majority (71.8%; n = 81) had secondary CNS lymphoma and 28.3% (n = 32) had primary CNS lymphoma.
Fludarabine and cyclophosphamide were the two most commonly used lymphodepleting chemotherapies. CAR-T doses ranged from 0.6 x 108 to 6 x 108.
Key findings
More than half (56.6%) of patients achieved complete response, 8.9% achieved partial response, 3.3% had stable disease and 39.8% experienced progressive disease.
Fourteen (21.9%) of the patients who achieved complete response and six (60%) of the patients who achieved partial response later developed disease progression.
Fourteen studies reported disease status at the time of CAR T-cell therapy.
Seventy-one patients (62.8%) had active disease at the time of infusion. More than half (53.5%) achieved complete response, 14.1% achieved partial response and 36.6% experienced progressive disease.
In the overall study population, researchers reported PFS rates of 72.1% at 1 month, 57% at 3 months, 44.2% at 6 months and 37.5% at 12 months.
Sixteen studies (n = 108) reported CRS incidence. Nearly three-quarters of patients (70.1%) developed grade 1 or grade 2 CRS, and 6.5% developed grade 3 or grade 4 CRS.
Sixteen studies (n = 109) evaluated neurotoxicity. Approximately one-third of patients (31.8%) developed grade 1 or grade 2 ICANS and 21.1% developed grade 3 or higher ICANS.
No patients died due to CRS or ICANS.
“We have been seeing very good outcomes with these patients. Unfortunately, most of them were not included in clinical trials,” Husnain told Healio. “Overall, the efficacy and safety data look promising, and I think more trials will start enrolling these patients on CAR-T clinical trials.”
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Husnain M, et al. LBA 9. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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