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 CD191 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.

Locatelli, F., Zugmaier, G., Mergen, N., Bader, P., Jeha, S., Schlegel, P. -., Bourquin, J. -., Handgretinger, R., Brethon, B., Rossig, C., Kormany, W. N., Viswagnachar, P., Chen-Santel, C., Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis, <<BLOOD ADVANCES>>, 2022; 6 (3): 1004-1014. [doi:10.1182/bloodadvances.2021005579] [https://hdl.handle.net/10807/228374]

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

Locatelli, Franco
Primo
Writing – Review & Editing
;
2022

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 CD191 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.
2022
Inglese
Locatelli, F., Zugmaier, G., Mergen, N., Bader, P., Jeha, S., Schlegel, P. -., Bourquin, J. -., Handgretinger, R., Brethon, B., Rossig, C., Kormany, W. N., Viswagnachar, P., Chen-Santel, C., Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis, <<BLOOD ADVANCES>>, 2022; 6 (3): 1004-1014. [doi:10.1182/bloodadvances.2021005579] [https://hdl.handle.net/10807/228374]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/228374
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 15
social impact