Consolidation with First and Second Allogeneic Transplants in Adults with Relapsed/Refractory B-ALL Following Response to CD19CAR T Cell Therapy
Authors: Aldoss Ibrahim , Shan Haoyue , Yang Dongyun , Clark Mary C , Al Malki Monzr M. , Aribi Ahmed , Sandhu Karamjeet S. , Salhotra Amandeep , Agrawal Vaibhav , Pourhassan Hoda , Koller Paul B. , Ali Haris , Artz Andrew , Amanam Idoroenyi , Karras Nicole , Pawlowska Anna , Murphy Lindsey , Palmer Joycelynne Michelle , Marcucci Guido , Stein Anthony , Pullarkat Vinod , Nakamura Ryotaro , Forman Stephen J. 
Published: December 2023

Introduction:CD19-targeted chimeric antigen receptor (CD19CAR) T cell therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR T cell therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). However, available data for post CAR T alloHCT in r/r B-ALL are limited, especially for the role of the second alloHCT post CAR T response among patients (pts) who relapsed following their first alloHCT.

Methods: We performed a retrospective analysis of adult pts with r/r B-ALL who responded to CD19CAR T cell therapy and underwent consolidation with alloHCT while in CR without interim therapy at City of Hope (COH) between 2016 and 2023. The decision to consolidate with alloHCT was based on the discretion of the treating physician and pt eligibility. We assessed overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) using Kaplan-Meier method on total pts and stratified by transplant time points (first vs. second).

Results: We identified 39 pts, of whom 24 (62%) and 15 (38%) received their firstand second alloHCT as consolidation post CAR T cells, respectively. The median age was 29 years (range: 19-67), 25 (64%) were male, 28 (72%) were Hispanic, and 25 (64%) had Ph-like ALL. Twenty-five (64%) pts received investigational CD19CAR T cell products. Disease status pre-lymphodepletion was isolated r/r (≥5% blasts) in the bone marrow (BM) in 21 (54%) pts, extramedullary disease +/- BM in 12 (31%) pts, and minimal residual disease (MRD)+ only in 6 (15%) pts. Blinatumomab and inotuzumab were administered previously to 67% and 18% of pts, respectively. At the time of alloHCT, the median number of prior lines of therapy was 5 (range: 2-7). Disease status at the time of alloHCT was CR1, CR2 or ≥CR3 in 6, 19 and 14 pts, respectively. All pts were MRD- prior to alloHCT except for 2 pts who converted to MRD+ just before alloHCT and 1 pt with unknown MRD status; all 3 pts received their first alloHCT. The median time from CAR T cell therapy until alloHCT was 91 days (range: 42-262). Conditioning regimen was myeloablative in 21 (54%) pts and specifically radiation-based in 20 (51%). Donors were unrelated in 22 (56%) and haploidentical in 9 (23%). Table 1 shows pts characteristics for those who underwent first and second alloHCT.

Overall, with a median follow up of 19.7 months, the 18-month OS, RFS, CIR and NRM were 65% (95%CI: 0.499-0.0843), 56% (95%CI: 0.407-0.765), 19% (95%CI: 0.092-0.405) and 25% (95%CI: 0.134-0.463), respectively. NRM at day 100 was 3% (95%CI: 0.004-0.192). Thirteen pts died post alloHCT; causes of death were relapsed ALL (n=4), sepsis (n=3), respiratory failure (n=2), graft-versus-host disease (n=1), HHV6 encephalitis (n=1), veno-occlusive disease (n=1) and toxoplasma encephalopathy (n=1). At 18 months, OS (59% vs. 75%, p=0.41), RFS (50% vs. 65%, p=0.49), CIR (25% vs. 1%, p=0.26), and NRM (25% vs. 25%, p=0.83) were comparable for those who underwent their first or second alloHCT post CD19CAR T cell therapy, respectively. Figure 1 shows the Kaplan-Meier analysis of OS.

Conclusions: We report low early NRM and favorable survival outcomes for alloHCT consolidation post response to CD19CAR T cell therapy in heavily pre-treated adult pts with r/r B-ALL, despite 5 median prior lines of therapy and Ph-like disease in over half of pts. Outcomes for second alloHCT were promising in this setting and comparable to first alloHCT.