Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study

I was a co-author on this manuscript as I contributed to the bone marrow blast count analysis.

Link to the article: https://doi.org/10.1182/bloodadvances.2016001925

Citation: DeAngelo, Daniel J., et al. “Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study.” Blood advances 1.15 (2017): 1167-1180.

Abstract:

This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics
of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic
leukemia. In phase 1, patients received InO 1.2 (n 5 3), 1.6 (n 5 12), or 1.8 (n 5 9) mg/m2
per cycle on days 1, 8, and 15 over a 28-day cycle (#6 cycles). The recommended phase 2 dose
(RP2D) was confirmed (expansion cohort; n 5 13); safety and activity of InO were assessed in
patients receiving the RP2D in phase 2 (n 5 35) and in all treated patients (n 5 72). The RP2D
was 1.8 mg/m2 per cycle (0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15), with reduction to
1.6 mg/m2 per cycle after complete remission (CR) or CR with incomplete marrow recovery (CRi).
Treatment-related toxicities were primarily cytopenias. Four patients experienced treatmentrelated venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS; 1 fatal). Two
VOD/SOS events occurred during treatment without intervening transplant; of 24 patients
proceeding to poststudy transplant, 2 experienced VOD/SOS after transplant. Forty-nine (68%)
patients had CR/CRi, with 41 (84%) achieving minimal residual disease (MRD) negativity. Median
progression-free survival was 3.9 (95% confidence interval, 2.9-5.4) months; median overall
survival was 7.4 (5.7-9.2) months for all treated patients, with median 23.7 (range, 6.8-29.8)
months of follow-up for all treated patients alive at data cutoff. Achievement of MRD negativity
was associated with higher InO exposure. InO was well tolerated and demonstrated high singleagent activity and MRD-negativity rates. This trial was registered at www.clinicaltrials.gov as NCT01363297.