Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis

Abstract

The safety and efficacy of blinatumomab, a CD3/CD19-directed bispecific molecule, were examined in an open-label, single-arm, expanded access study (RIALTO). Children (>28 days and <18 years) with CD19+ relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) received up to 5 cycles of blinatumomab by continuous infusion (cycle: 4 weeks on/2 weeks off). The primary end point was incidence of adverse events. Secondary end points included complete response (CR) and measurable residual disease (MRD) response within the first 2 cycles and relapse-free survival (RFS), overall survival (OS), and allogeneic hematopoietic stem cell transplant (alloHSCT) after treatment. At final data cutoff (10 January 2020), 110 patients were enrolled (median age, 8.5 years; 88% had ≥5% baseline blasts). A low incidence of grade 3 or 4 cytokine release syndrome (n = 2; 1.8%) and neurologic events (n = 4; 3.6%) was reported; no blinatumomab-related fatal adverse events were recorded. The probability of response was not affected by the presence of cytogenetic/molecular abnormalities. Median OS was 14.6 months (95% confidence interval [CI]: 11.0-not estimable) and was significantly better for MRD responders vs MRD nonresponders (not estimable vs 9.3; hazard ratio, 0.18; 95% CI: 0.08-0.39). Of patients achieving CR after 2 cycles, 73.5% (95% CI: 61.4%-83.5%) proceeded to alloHSCT. One-year OS probability was higher for patients who received alloHSCT vs without alloHSCT after blinatumomab (87% vs 29%). These findings support the use of blinatumomab as a safe and efficacious treatment of pediatric R/R B-ALL. This trial was registered at www.clinicaltrials.gov as #NCT02187354.

Graphical abstract

Figure 1.

Relapse-free survival. (A) RFS was calculated relative to the date of bone marrow aspiration when CR was detected for the first time to the event date (date of the bone marrow aspiration at which hematologic relapse was first detected, the date of the diagnosis on which the hematologic or extramedullary relapse was documented, or the date of death because of any cause, whichever occurred earlier). (B) RFS was analyzed according to MRD response using the Kaplan-Meier method. (C) RFS was analyzed according to alloHSCT status after blinatumomab using a Simon-Makuch 71-day landmark analysis..

Figure 2.

OS was censored at 18 months because only a subgroup of nontransplanted patients was followed beyond 18 months. (A) OS was defined from the start of blinatumomab infusion until death. (B) OS was analyzed according to MRD response using the Kaplan-Meier method. (C) OS was analyzed according to alloHSCT status after blinatumomab using a Simon-Makuch 60-day landmark analysis. (D) OS was analyzed according to donor type for alloHSCT after blinatumomab treatment. Vertical bars indicate censoring.

Figure 2.

OS was censored at 18 months because only a subgroup of nontransplanted patients was followed beyond 18 months. (A) OS was defined from the start of blinatumomab infusion until death. (B) OS was analyzed according to MRD response using the Kaplan-Meier method. (C) OS was analyzed according to alloHSCT status after blinatumomab using a Simon-Makuch 60-day landmark analysis. (D) OS was analyzed according to donor type for alloHSCT after blinatumomab treatment. Vertical bars indicate censoring.

Figure 3.

Cumulative incidence of transplant-related mortality for patients who achieved best response in the first 2 cycles.