Donor derived CD19 CAR-T cell for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

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Recurrency after alloHSCT is still the most common reason for treatment failure. The salvage treatments after recurrence includes donor lymphocyte infusion(DLI) and second HSCT. However, the 1-year overall survival rates are only 20.74%1 and 23%2, respectively. There are great needs for an effective or alternative therapy. CD19 CAR-T cell therapy has produced impressive outcomes for relapsed/refractory (R/R) B cell hematological malignancies3,4. The safety and efficacy of donor derived CD19 CAR-T cell therapy to relapsed B-ALL after alloHSCT remain unclear.

Inspired by this, we designed a retrospective clinical trial which aggregated clinical data from totally nine medical centers in China, making it the largest reported case number of recurrent B-ALL (43 subjects), median follow-up of survivors was 18 months (range, 6-47 months). The outcomes are optimistic, 34 subjects (79%; 95% confidence Interval [CI], 66, 92%) achieved a complete remission. CRS occurred in 38 (88% [78, 98%]) and was ≥ grade-3 in 7. Two subjects died from multi-organ failure and CRS. Nine subjects (21% [8, 34%]) developed ≤ grade-2 ICANS with no cases > grade-2. Two subjects developed ≤ grade-2 acute GvHD. 1-year EFS and survival was 43% (25, 62%). In subjects with a complete remission 1-year probability of CIR was 41% (25, 62%; N =43) and 1-year EFS and survival was 59% (37, 81%; N =43).

Therapy of CD19-positive B-cell ALL relapsing after alloHSCT with donor-derived anti-CD19 CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes are comparable and sometimes better compared with those achieved with stopping immune suppression, DLI and/or with a second allotransplant from the same or different donor. Safety and efficacy of these strategies can only be accurately compared in a randomized trial.

 

  1. Vaezi M, Zokaasadi M, Shahsavari Pour S, et al. The Role of Donor Leukocyte Infusions in the Treatment of Relapsed Acute Leukemia after Allogeneic Stem Cell Transplantation: A Retrospective Analysis. Int J Hematol Oncol Stem Cell Res. 2018;12: 185–191.
  2. LM Poon, R Bassett Jr, G Rondon, et al. Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia. Bone Marrow Transplant.2013;48:666-70.
  3. Liu D. CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy. J Hematol Oncol. 2019;12:113.
  4. Schuster SJ. CD19-directed CAR T cells gain traction. Lancet Oncol. 2019;20:2–3.

Xi Zhang

Director of Hematology, Xinqiao Hospital

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