Transplant Status May Affect CAR-T Therapy Outcomes in CLL and B-ALL

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Transplant-naive patients were more likely to achieve an optimal drug response — but were also more prone to severe cytokine release syndrome and neurotoxicity.
Transplant-naive patients were more likely to achieve an optimal drug response — but were also more prone to severe cytokine release syndrome and neurotoxicity.

Hematopoietic stem cell transplant (HSCT) before chimeric antigen receptor (CAR) T-cell therapy (CAR-T) may influence the likelihood of an optimal drug response and the development of severe cytokine release syndrome (CRS) and neurotoxicity, a meta-analysis showed. The study was published online in Medical Oncology on September 11, 2018.1

“Given that many potential candidates for CAR T-cell therapy will have undergone HSCT, it is important to determine whether prior transplant status impacts the efficacy and safety of CAR T-cell therapy,” the study authors wrote.

To determine the influence of transplant status, researchers identified trials that had evaluated autologous CD-19–directed CAR-T therapy in patients with relapsed/refractory B-lineage acute lymphoblastic leukemia (B-ALL) or B-cell chronic lymphocytic leukemia (CLL). Only trials that had been conducted in 2011 or later and had enrolled both HSCT-naive and prior-HSCT patients were included in the analysis.

In total, 6 nonrandomized, noncontrolled, single-arm trials were identified for analysis. Optimum response data were pooled from all 6 trials, whereas severe CRS data were pooled from 5 trials and neurotoxicity data from 4 trials.

The analysis revealed that HSCT-naive patients had an increased likelihood for achieving an optimum response (ie, minimal residual disease-negative complete remission). The result, however, was not statistically significant (OR = 1.57; 95% CI 0.54–4.61; P = 0.41). HSCT-naive patients also had a slightly increased likelihood of developing severe CRS (OR = 1.41; 95% CI 0.51–3.94; P = 0.51) or neurotoxicity (OR = 1.37; 95% CI 0.28–6.77; P = 0.70), but neither finding was statistically significant.

“Due to low sample sizes and high risk of bias among included studies, trustworthy conclusions cannot be drawn from this review's findings,” the authors cautioned. “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.”

Reference

  1. Nagle K, Tafuto B, Palladino Kim L, and Parrott JS. Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic review and meta-analysis [published online September 11, 2018]. Med Oncol. doi: 10.1007/s12032-018-1204-6
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