Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) Following Blinatumomab-Induced Remission in Pediatric Patients with Relapsed/Refractory (r/r) B-Precursor Acute Lymphoblastic Leukemia (ALL): Preliminary Results from a Phase I/II Stud
2015-01-22

The prognosis for patients (pts) with r/r ALL is poor especially after transplantation. Blinatumomab, an investigational bispecific T-cell engager (BiTE®) antibody construct that redirects T cells to CD19+ B cells resulting in serial lysis, has shown antileukemia activity in pts with r/r ALL. We evaluated the transplantation rate after blinatumomab-induced remission, in pediatric patients with r/r ALL characterized by negative prognostic factors, such as refractory disease and prior alloHSCT. In this single-arm study, eligible pts were 2−18 yrs old and had an M3 marrow with B-precursor ALL that was refractory, in ≥2nd marrow relapse, or any marrow relapse after HSCT; and no CNS leukemia. A stepwise dose (wk 1: 5 μg/m2/d; thereafter: 15 μg/m2/d) of blinatumomab was given by continuous IV infusion (4 wks on/2 wks off) for up to 5 cycles. Primary endpoint was complete remission (CR) rate within 2 cycles. Secondary endpoints were alloHSCT rate, relapse-free survival (RFS), overall survival (OS), and adverse events (AEs). 39 pts received blinatumomab. Median (range) age was 9 (2–16) yrs. 69% of pts had ≥50% bone marrow blasts. 41% had 1 prior salvage, 41% had ≥2 prior salvages and 18% were primary refractory or had refractory relapse. 87% of pts enrolled had relapsed within 6 months after the last remission. Among pts with prior alloHSCT (64%), 16% had 1 relapse and 50% had ≥2 relapses. Of 12 pts (31%; 95% CI, 17%–48%) who reached CR within the first 2 cycles, 6 (50%) proceeded to alloHSCT. 5 pts who did not respond to blinatumomab received alloHSCT after treatment was ended. Donors included haploidentical parents (n=9), a sibling (n=1) and an unrelated donor (n=1). AlloHSCT were performed at 8 different centers. Conditioning regimens included 5 myeloablative, 5 reduced intensity, and 1 unknown regimen. Median (95% CI) RFS was 5.6 (2.6–12.1) months among blinatumomab responders and 6.5 (2.2–7.7) months among responders receiving alloHSCT (measured from the time of alloHSCT). At 6-month follow-up, median (95% CI) OS was 4.3 (3.6–8.1) months among all pts and 7.7 (0.45–NE) months among pts receiving alloHSCT (measured from the time of alloHSCT). 100-day mortality rate post alloHSCT was 10%. The most common AEs among all pts included pyrexia (74%), anemia (33%), nausea (31%), headache (28%) and hypertension (26%). Anemia (26%), pyrexia (21%), increased alanine aminotransferase or aspartate aminotransferase (18% each) and febrile neutropenia (15%) were the most common grade ≥3 AEs. 3 (8%) pts (2 with grade 3 events) had cytokine-release syndrome. In this phase I/II study, blinatumomab has shown promising antileukemia activity in pediatric patients with r/r B-precursor ALL, most of whom had prior alloHSCT and/or were refractory. Half of pts who achieved CR in response to blinatumomab proceeded to alloHSCT, suggesting that blinatumomab may provide a therapeutic option to bridge this patient population to alloHSCT.