Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia

Arend Von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M. Trippett, Carmelo Rizzari, Peter Bader, Maureen M. O'brien, Benôit Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R. Rheingold, Todd Michael Cooper, Christian M. Zwaan, Phillip Barnette, Chiara Messina, Ǵerard Michel, Steven G. Dubois, Kuolung HuMin Zhu, James A. Whitlock, Lia Gore

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

450 Citaten (Scopus)

Samenvatting

Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. Weevaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children , 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 mg/m2d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 mg/m2d for the first 7 days, followed by 15 mg/m2d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade $ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

Originele taal-2Engels
Pagina's (van-tot)4381-4389
Aantal pagina's9
TijdschriftJournal of Clinical Oncology
Volume34
Nummer van het tijdschrift36
DOI's
StatusGepubliceerd - 20 dec. 2016
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia'. Samen vormen ze een unieke vingerafdruk.

Citeer dit