Outcomes of Hematopoietic Stem Cell Transplantation (HSCT) Among Adults with Relapsed/Refractory (r/r) Acute Lymphoblastic Leukemia (ALL) Achieving Remission with Blinatumomab

Allogeneic HSCT is the only known curative therapy for patients with relapsed ALL and is most effective among those who achieve a remission to salvage therapy before transplant conditioning. However, outcomes of HSCT remain unsatisfactory in patients who are transplanted in the setting of refractory disease, relapse, 2nd or later remission or minimal residual disease (MRD) positivity. Blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct, has shown antileukemia activity in patients with r/r ALL. Here we report outcomes from a multicenter, open-label phase 2 study in patients with r/r ALL who received HSCT after achieving complete remission (CR) or CR with partial hematologic recovery (CRh) with blinatumomab. Individual patient data were reviewed for HSCT outcomes; graft-versus-host disease (GvHD) outcomes were not collected. Adults with Philadelphia chromosome-negative r/r B-precursor ALL (primary refractory, relapsed <12 months after first remission or HSCT or ≥2 salvage treatments) were eligible. Blinatumomab was given by continuous IV infusion for up to 5 cycles (1 cycle: 4 weeks on, 2 weeks off). Factors specific to HSCT were not part of the protocol. CR/CRh in the first 2 cycles was the primary endpoint. Secondary endpoints included HSCT realization rate, 100-day mortality following HSCT, overall survival (OS) and relapse-free survival (RFS). Baseline characteristics of the HSCT recipients in remission are summarized in the table. Of 189 patients treated with blinatumomab, 83 (44%) achieved CR/CRh during the first 2 cycles. Median OS follow-up was 13.4 months post-HSCT. Overall HSCT realization rate in remission was 41% (34/83): 50% (27/54) for HSCT-naïve patients, 24% (7/29) for patients with prior HSCT. HSCT recipients received a median of 2 blinatumomab cycles (range, 1–5) before HSCT. Details of conditioning regimens were provided for 28 patients (data unavailable: 6 patients): 54% myeloablative, 43% reduced intensity, and 4% unknown. Conditioning regimens were initiated a median of 23 days (range, 8–60) after the end of blinatumomab treatment. 80% of HSCT recipients had MRD response (<10-4) and 77% had complete MRD response (undetectable) before HSCT. 4 (12%) patients died within 100 days post-HSCT in remission due to infection (n=3) and GvHD (n=1). Kaplan-Meier estimates for cumulative OS and RFS at 12 months post-HSCT were 73% (95% CI, 55–85) and 53% (95% CI, 34–69), respectively. In this phase 2 study, 41% of responders to blinatumomab received HSCT in remission; 80% achieved an MRD response before HSCT. Blinatumomab can be administered in close temporal proximity to myeloablative or reduced intensity conditioning regimens without evidence of increased treatment-related mortality. In this group of patients with r/r ALL, blinatumomab served as an effective salvage regimen and bridge to transplant.TableCharacteristics of HSCT recipients in remission (N=34)Median years (range)31 (18–65)Male, n (%)19 (56)Prior relapses before blinatumomab and HSCT, n (%)04 (12)I21 (62)28 (24)>21 (3)Prior saivage therapies, n(%)09 (27)17 (50)25 (15)>23 (9)Donor, n (%)Unrelated24 (71)Related8 (24)Unknown2 (6) Open table in a new tab