In a retrospective study of patients with aggressive non-Hodgkin lymphoma (NHL) who received bridging radiation-containing treatment (BRT) before CAR T-cell therapy, the bridging therapy significantly reduced predictors of poor post-CAR T outcomes with minimal toxicity and may be able to “convert” patients at high risk for progression to a more favorable risk state. The study was published online in Transplantation and Cell Therapy in December.
Brandon S. Imber, MD, and colleagues at Memorial Sloan Kettering Cancer Center reviewed the medical records of all patients with aggressive NHL who were consecutively treated between 2017 and 2021, received BRT before commercial CAR T-cell therapy, and underwent interim positron emission tomography (PET) in between BRT and CAR T-cell infusion. Of 41 eligible patients, pre- and post-BRT PET imaging was available for 32.
BRT “significantly improved established high-risk parameters of post-CAR-T therapy progression,” including in-field median metabolic tumor volume (MTV), maximum standard uptake value, diameter, and lactate dehydrogenase (LDH), the authors write. ““LDH, a serologic correlate for overall disease burden, was significantly reduced after BRT,” the authors write. Sixty-one percent of patients had a complete response following CAR T therapy, while 15% had a partial response. Among the 33 patients with diffuse large B-cell lymphoma, the overall response rate was 79%, median progression-free survival 20 months, and median overall survival not reached. Toxicities possibly attributable to BRT occurred in 76% of patients; 87% of these toxicities were low grade and none were grade 4 or 5.
“Similar PFS and OS in patients with initially low MTV and those with newly achieved low MTV after BRT suggests the ability to “convert” poor-risk patients to better risk, although studies with larger cohorts are needed to confirm this finding,” Imber and colleagues write. They conclude: “Further work with larger cohorts and prospective comparison is needed to investigate the hypothesis raised here that BRT may alter post-CAR-T patterns of failure and post-CAR-T patient outcomes.”
- Hubbeling H, Silverman EA, Michaud L, et al. Bridging Radiation Rapidly and Effectively Cytoreduces High-Risk Relapsed/Refractory Aggressive B Cell Lymphomas Prior to Chimeric Antigen Receptor T Cell Therapy. Transplant Cell Ther. 2022 Dec 30;S2666-6367(22)01870-X. doi: 10.1016/j.jtct.2022.12.021. Online ahead of print.