Inotuzumab ozogamicin therapy for measurable residual disease in adult acute lymphoblastic leukemia

Abstract

Inotuzumab ozogamicin, an anti-CD22 antibody-drug conjugate, has demonstrated high response rates and measurable residual disease (MRD)-negativity in acute lymphoblastic leukemia (ALL). This phase 2 single-center study evaluated inotuzumab 0.6 mg/m2 day 1 and 0.3 mg/m2 day 8 (cycle 1) followed by 0.3 mg/m2 days 1 and 8 (cycles 2–6) for adults with B-cell ALL in morphologic remission with detectable MRD (≥1 × 10−4 by multiparameter flow cytometry, BCR::ABL1 transcripts ≥0.01% by polymerase chain reaction [PCR], or ≥1 × 10−6 by next-generation sequencing [NGS]). Thirty-seven patients (median age 49 years) were treated, including 17 with Philadelphia-chromosome (Ph)-negative ALL and 20 with Ph-positive ALL. Twenty-eight patients (76%) were in first remission (CR1). Overall, 26 patients (70%) achieved MRD-negativity, including 76% of patients with Ph-negative ALL and 65% of patients with Ph-positive ALL. The NGS MRD-negativity rate was 73%. With a median follow-up of 50 months, the median overall survival (OS) was 61 months, with a median relapse-free survival (RFS) of 40 months. Patients treated in CR1 vs CR2+ had a median OS that was not reached versus 14 months, respectively (p = 0.056). Three cases (8%) of non-fatal sinusoidal obstructive syndrome (SOS) were observed. Inotuzumab was safe and effective at eradicating MRD.