Clinical Outcome with Allogeneic Hematopoietic Stem Cell Transplantation after Blinatumomab or Inotuzumab Ozogamicin in Patients with B-Cell Acute Lymphoblastic Leukemia: Real World Experience

Abstract

Introduction Blinatumomab (Blina) and inotuzumab ozogamicin (Ino) have shown remarkable responses in relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL), however, a significant number of patients (pts) relapse. Prior reports suggest that allogeneic hematopoietic stem cell transplantation (SCT) consolidation after Blina/Ino may be associated with increased transplant related complications. To address this issue, we assembled a large retrospective multi-center cohort of RR ALL pts who received SCT after Blina/Ino. Methods Medical records of RR ALL pts who received SCT after Blina or Ino at 11 academic transplant centers across USA were reviewed. These pts were evaluated for response and toxicity after SCT. Results From December 2014 to May 2019, 223 and 86 pts who received Blina and Ino, respectively, for RR ALL outside clinical trials were identified. Among them 85 (38%) pts in the Blina group (gp) and 21 (25%) pts in the Ino gp who achieved remission and underwent SCT were included in this analysis. Median age of pts in the Blina and Ino gp was 59 (range [R], 18-72) and 43 (R, 20-75) years, respectively. Median number (no.) of therapies (Rx) prior to SCT in Blina and Ino gp was 2, ranging from 2-5 and 2-6, respectively. Five (6%) and 2 (5%) pts in the Blina and Ino gp, respectively, received second SCT. Median time from remission to SCT in Blina gp was 1.7 months (mo) (R, 0.20 to 13.2) and in Ino gp was 4.3 mo (R, 1-13.3). In the Blina and Ino gp: 36.5% vs. 38%, 42% vs. 42%, 15% vs. 9.5% and 6% vs. 9.5% had matched related donor (MRD), matched unrelated donor (MUD), haploidentical and cord blood SCT, respectively. Acute graft versus host disease (aGVHD), chronic (c) GVHD, veno-occlusive disease (VOD) and infectious complications post SCT were observed in 28 (33%), 14 (16.5%), 2 (2%) and 12 (14%) pts, respectively, in the Blina gp. While in the Ino gp, 8 (38%), 1 (5%), 3 (14%) and 4 (19%) pts had these complications, respectively. Six (7%) and 2 (9%) pts had TRM within 100 days of SCT in Blina and Ino gp, respectively. The median PFS and OS in Blina gp was not reached (NR); 66% were progression free and 62% were alive at 2 yrs (Fig 1 A & B). Similarly, median PFS and OS in the Ino gp was NR; 53% were progression free at 6 mo and 53% were alive at 1 yr mark (Fig 1 C & D). In the Blina gp, history of CRS (p= 0.41), no. of prior Rx (p= 0.5), time from response to SCT (p=0.48), and type of donor (p= 0.7) were not significantly associated with GVHD. Similarly, in the Ino gp, no. of prior Rx (p= 0.6), time from response to SCT (p=0.84), type of donor (p= 0.9) were not significantly associated with GVHD. Occurrence of VOD in the Ino gp was not significantly associated with type of donor (p= 0.3), second SCT (p= 0.1), no. of prior Rx (p= 0.6), myeloablative conditioning (p> 0.9) or time from response to SCT (p= 0.5). Conclusion Our real-world analysis suggests that SCT is feasible and effective after Blina or Ino in pts with RR ALL.