A real-world multi-institution experience of standard versus alternative dosing regimens of inotuzumab ozogamicin for relapsed/refractory paediatric B-cell acute lymphoblastic leukaemia.

Inotuzumab ozogamicin (InO) is approved by the U.S. Food and Drug Administration (FDA) for relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL), with a standard schedule of 1.8 mg/m2 fractionated into three doses for cycle 1. Alternative dosing with fewer doses or lower cumulative doses may be considered to minimize toxicity or expedite transition to consolidative therapy, though data on the efficacy and toxicity of this approach are limited. We conducted a multi-institutional retrospective analysis of 72 paediatric, adolescent and young adult (AYA) patients receiving at least one InO dose; 41 with standard dosing and 31 with alternative dosing. Between the two approaches, standard dosing was associated with improved composite complete response (CRc); however, there was no difference in ability to proceed to consolidative cellular therapy, nor differences in 2-year event-free or overall survival. Ten per cent of patients experienced sinusoidal obstruction syndrome (SOS), all following haematopoietic stem cell transplant. Most cases occurred in patients receiving standard InO dosing; however, given the overall few cases, it is unclear if this is due to a difference in dosing regimen. In conclusion, this large real-world study of InO use in the paediatric/AYA R/R B-ALL population suggests using alternate InO dosing strategies can successfully bridge patients to consolidative therapy with no difference in outcomes compared with standard dosing.