M-05: Effect of Transplant Status in CD19-Targeted CAR T-Cell Therapy: A Systematic Review and Meta-Analysis
Rutgers University United States
To evaluate the likelihood of achieving minimal residual disease (MRD)-negative complete remission and incidence of severe cytokine release syndrome (sCRS) and neurotoxicity for CAR T-cell subjects who had undergone prior hematopoietic stem cell transplant (HSCT) versus those who were HSCT-naive.
ORAL PRESENTATION: 1:15PM
A systematic review was conducted of studies from PubMed, the Cochrane Library, and bibliographies. Studies used CD19-directed CAR T-cell therapy for relapsed/refractory B-cell cancers and identified prior HSCT status when reporting outcomes. Six studies were included in the primary meta-analysis.
Odds ratios and 95% confidence intervals for each study and pooled estimates were calculated using binary random-effects models. The pooled odds ratios calculated for MRD-negative complete remission was 1.864 in favor of HSCT-naïve subjects (95% CI 0.622 to 5.588). The pooled odds ratios for sCRS and neurotoxicity were 1.422 (95% CI 0.59 to 3.424) and 1.236 (95% CI 0.48 to 3.189) respectfully, both in favor of HSCT-naïve subjects. The results of this review demonstrate a minor, though non-statistically significant, increased likelihood for HSCT-naïve subjects to experience MRD-negative complete remission after treatment with CAR T-cell therapy. Subgroup analyses, though also non-statistically significant, suggest that the pooled estimate favoring HSCT-naïve subjects might be further bolstered by administration of cyclophosphamide/fludarabine (Cy/Flu) lymphodepleting chemotherapy, pediatric/young adult age, and use of retroviral-based CAR T-cell products.
While the pooled estimates showed a minor advantage among HSCT-naïve subjects for achieving MRD-negative CR, as well as a slight increased likelihood for experiencing sCRS and neurotoxicity, findings were non-statistically significant. Therefore, additional trials are needed to determine whether these tendencies favoring HSCT-naïve subjects are statistically significant. The tendency for HSCT-naïve subjects to derive improved efficacy outcomes, coupled with more severe toxicities, from CAR T-cell therapy are important clinical findings that may influence treatment decision-making if validated. Likewise, the subtle disadvantage noted among prior-HSCT subjects warrants further investigation. While trustworthy conclusions cannot be drawn from this review’s findings, these findings undoubtedly support 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.