CAR-based Cellular Therapy: clinical ePoster with Audio

O035 - PRE-TRANSPLANT MRD NEGATIVITY PREDICTS FAVORABLE OUTCOMES OF CAR-T THERAPY FOLLOWED BY HAPLOIDENTICAL HSCT FOR RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: A MULTI-CENTER RETROSPECTIVE STUDY (ID 1222)

Authors
  • M. Zhao
  • G. Wei
  • Y. Hu
  • H. Zhao
  • H. Jing
  • A. Liang
  • Y. Li
  • X. Song
  • J. Chen
  • Q. Zhang
  • Q. Cui
  • J. Shi
  • X. Li
  • Y. Luo
  • M. Mohty
  • A. Nagler
  • H. Huang
  • J. Yang
  • S. Hao
  • D. Blaiser
  • A. Chang

Abstract

Background: Recently chimeric antigen receptor T cells (CAR-Ts) have been successful in improving treatment outcomes for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) by targeting CD19 or CD22, but relapse after CAR-T therapy is supposed a main obstacle. It remains controversial whether these patients could benefit from consolidative allo-HSCT after CAR-T therapy.
 

Methods: We designed a multi-center retrospective study to assess the efficacy and safety profiles of CAR-T therapy followed by haplo-HSCT from 11 domestic centers. Patients with minimal residual disease (MRD) negative complete remission (CR) after CAR-T therapy were divided into 3 groups: CAR-T treatment without transplant (Non-transplant group), haplo-HSCT with pre-transplant MRD negativity (MRD- group) and haplo-HSCT with pre-transplant MRD positivity (MRD+ group).
 

Results: 80, 41 and 17 patients were included in non-transplant group, MRD- group and MRD+ group, respectively. 2-year leukemia free survival (LFS) were 47.2%, 48.5% and 88.5% in non-transplant group, MRD+ group and MRD- group, respectively. Statistically higher LFS were found in MRD- group in contrast to non-transplant group (p=0.0019) and MRD+ group (p=0.0065), but no statistical difference were found between non-transplant group and MRD+ group (p=0.7424) (Figure 1A). 2-year overall survival (OS) were 46.7%, 50.7% and 87.8% in non-transplant group, MRD+ group and MRD- group, respectively. Statistically higher OS were found in MRD- group in contrast to non-transplant group (p=0.0048) and MRD+ group (p=0.0267), but no statistical difference between non-transplant group and MRD+ group (p=0.6066) (Figure 1B). Haplo-HSCT is the only independent factor associated with poor LFS (P< 0.05) and OS (P< 0.05) between non-transplant group and transplant group (MRD+ group and MRD- group together). MRD positivity at the time of haplo-HSCT is the only independent factor associated with poor LFS (P< 0.05) and OS (P< 0.05) in transplant patients. There were no statistical difference about cumulative incidence (CI) of grade III~IV aGVHD, CIs of cGVHD requiring systemic steroid therapy between the 2 transplant groups. The 1-year and 2-year CIs of infection including bacteria, CMV viremia and EBV viremia were not statistically significant among the 3 groups.
 

Conclusions: Haplo-HSCT after CAR-T treatment could greatly improve LFS and OS without increasing risks of treatment-related toxicity. Moreover, we confirmed that achieving pre-transplant MRD negativity after CAR-T treatment is a suitable basis for haplo-HSCT.

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