Inotuzumab Ozogamicin Outcomes in ALL Validated Outside of Clinical Trials

Reasonable remission rates were seen when inotuzumab ozogamicin was administered as a salvage therapy to patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), with mean (SD) survival rates of 51.7% (8.1%) overall and 32.4% (8.0%) event-free, according to new research in Blood Cancer Journal.¹ These real-world data are helping to fill a data gap for such evidence currently left by limited studies in this disease and medication, which have been concentrated in clinical trial settings.^2-4

Forty-nine patients with B-ALL who were treated between January 2020 and December 2024 and who received inotuzumab ozogamicin were included in this analysis. Their median age was 24 years (range, 6-68), and most were male patients (79.5%; n = 39). Twenty-four (n = 48.9%) received inotuzumab ozogamicin for very early/early relapsed disease, 9 (18.4%) for late relapsed disease, and 7 (14.3%). The remaining 9 patients (18.4%) received inotuzumab ozogamicin for refractory disease.

Forty-six of the 49 patients had cytogenetic analysis performed, and of these, 22 (44.9%) had abnormal results. From among these 22 patients, 6 had Philadelphia-positive B-ALL; 8, high-risk cytogenetics; 2, hypodiploidy, which in B-ALL is 44 chromosomes or fewer⁵; 5, complex karyotype; and 1, KMT2A-rearranged ALL.

Overall, patients received inotuzumab ozogamicin in 1 of 3 ways: fixed doses of a 1-mg vial on days 1, 8, and 15 of a treatment cycle (n = 25); fixed doses of a 1-mg vial on days 1 and 15 (n = 2); or dosed per body surface area (n = 22). Nonresponders received a lower dose compared with responders; median doses were 1.54 mg/m²/cycle (range, 0.61-1.82; P = .42) vs 1.72 mg/m²/cycle (range, 1.23-2.1). A subanalysis conducted among the patients for whom CD22 data were available showed that expression was lower in the nonresponders compared with the responders: 94.92% (range, 1.13%-99.8%; P = .46) vs 98.3% (range, 16.9%-99.9%).

More than half of patients (57.14%; n = 28) had complete remission (CR) or CR with incomplete recovery, according to European LeukemiaNet criteria. Of this group, 71.4% (n = 20) reached minimal residual disease–negative status, and 67.8% (n = 19) followed inotuzumab ozogamicin with allogeneic stem cell transplant (ASCT; n = 18) or chimeric antigen receptor (CAR) T-cell therapy (n = 1). The median time between the last dose of inotuzumab ozogamicin and transplant was 45 days (range, 30-120).

Ten patients developed hepatic sinusoidal obstruction syndrome (SOS), which is veno-occlusive disease of the liver,⁶ and 9 of these cases occurred after transplant. Patients who developed severe SOS received a median dose of 1.79 mg/m²/cycle (range, 1.51-2.00) vs 1.61 mg/m²/cycle (range, 0.75-2.10). Statistically significant correlations were not seen between the occurrence of SOS and total or cumulative doses of inotuzumab ozogamicin or the time between the last dose and transplant. The condition did resolve in 5 patients, and their median survival was 14 months (range, 2-27).

In addition to the previously mentioned overall survival (OS) rate of the entire cohort, patients who underwent ASCT had a median OS of 68.4% (10.7%). The median follow-up for this cohort was 20.1 months (range, 2.0-33.5).

Comparing their findings to previous research in which patients received fractionated doses of inotuzumab ozogamicin, the present study authors noted that it is possible to reduce the risk of SOS with the method and to combine it with less hepatotoxic chemotherapy compared with higher-dose exposure—all while maintaining antileukemic efficacy. Peak calicheamicin exposure and endothelial injury can also be mitigated.

The authors conclude that despite their positive findings, “that [inotuzumab ozogamicin] salvage in R/R B-ALL is associated with reasonable remission rates, even when less than recommended doses were used, enabling a subsequent transplant or cell therapy in these patients in our real-world cohort,” additional analyses are needed on optimal combinations of fractionated inotuzumab ozogamicin and chemotherapy. This may help to reduce posttransplant SOS and/or relapse.

Limitations on these findings are the small sample size and the short follow-up.

References

1. Ravindranath A, Pandit V, Kulkarni U, et al. Real world outcomes with the use of inotuzumab ozogamicin in relapsed/refractory B cell acute lymphoblastic leukemia. Blood Cancer J. 2025;15(1):216. doi:10.1038/s41408-025-01448-w
2. Badar T, Szabo A, Wadleigh M, et al. Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with inotuzumab ozogamicin. Clin Lymphoma Myeloma Leuk. 2020;20(8):556-560.e2. doi:10.1016/j.clml.2020.03.004
3. Moribe T, Xu L, Tajima K, Yonemoto N. Real-world treatment patterns of novel drugs in relapsed or refractory acute lymphoblastic leukemia patients in Japan. Future Oncol. 2023;19(19):1343-1356. doi:10.2217/fon-2022-1314
4. Lecat CSY, Besley C, Hough RE, et al. Inotuzumab ozogamicin versus FLAG-Ida in the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia – real-world resource use data. Leuk Lymphoma. 2020;61(2):491-493. doi:10.1080/10428194.2019.1672057
5. Molina O, Bataller A, Thampi N, et al. Near-haploidy and low-hypodiploidy in B-cell acute lymphoblastic leukemia: when less is too much. Cancers (Basel). 2021;14(1):32. doi:10.3390/cancers14010032
6. Hepatic sinusoidal obstruction syndrome (veno-occlusive disease) in adults. UpToDate. Updated February 22, 2024. Accessed February 5, 2026. https://www.uptodate.com/contents/hepatic-sinusoidal-obstruction-syndrome-veno-occlusive-disease-in-adults