CAR-T Therapy Efficacy Based on Transplant Status in Certain Leukemias

The transplant statuses of patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) or B-cell chronic lymphocytic leukemia (CLL) may influence the outcomes they have with chimeric antigen receptor (CAR) T-cell therapy, according to the results of a recent study by Kathleen Nagle, MS, CCRP, Global Study Manager II, Covance, Princeton, New Jersey, and colleagues (Med Oncol. 2018;35[11]:144).

“Many patients have undergone prior hematopoietic stem cell transplant (HSCT), yet effects of transplant status on CAR T-cell therapy efficacy and safety have not been reported,” explained Ms Nagle and colleagues.

To determine the probability of optimal outcomes, severe cytokine release syndrome (CRS), and neurotoxicity in patients receiving CAR-T therapy who have and have not undergone HSCT, they identified clinical trials in which patients with relapsed or refractory B-ALL or CLL received autologous CD-19–directed CAR-T therapy.

Using ClinicalTrials.gov, Cochrane Library, and PubMed, Ms Nagle and colleagues identified 6 nonrandomized, single-arm studies that took place during or after 2011 for analysis. Optimum response (ie, no minimal residual disease and complete remission) data were pooled from all 6 studies, and data regarding severe CRS and neurotoxicity were pooled from 5 and 4 trials, respectively.

According to the analysis, when compared with patents who had undergone HSCT, those who were HSCT-naïve had a higher proclivity for achieving optimum response and increased likelihood for severe CRS and neurotoxicity compared with those who had undergone HSCT.

However, Ms Nagle and colleagues posited that these findings were not statistically significant. They also reported that any differences in the efficacy and safety of CAR-T therapy use between the 2 arms cannot be attributed to transplant status.

“Due to low sample sizes and high risk of bias among included studies, trustworthy conclusions cannot be drawn from this review’s findings,” Ms Nagle and colleagues concluded.

“However, these findings are suggestive of the need for additional clinical trials to more clearly understand the relationship of prior transplant status on efficacy and safety of CAR T-cell therapy,” they added.—Hina Khaliq