Liver Elasticity Assessment and SOS Risk in ALL Patients Treated with Inotuzumab Ozogamicin

Overview

This study evaluated baseline liver elastography in 50 adults with B-cell ALL treated with Mini-HyperCVD-InO-blinatumomab, finding low incidence of sinusoidal obstruction syndrome (SOS) and severe liver toxicity. Baseline shear wave velocity (SWV) >1.7 m/s did not predict grade ≥3 hepatic adverse events, and only one patient developed SOS during follow-up.

Background

Inotuzumab ozogamicin (InO) is an anti-CD22 antibody-drug conjugate improving outcomes in relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) but is associated with hepatic toxicity, notably sinusoidal obstruction syndrome (SOS). SOS incidence post-InO exposure and hematopoietic stem cell transplantation (HSCT) has been reported up to 20%. Liver elastography, measuring liver stiffness via shear wave velocity (SWV), is a non-invasive tool that may detect early liver injury and portal hypertension related to InO and HSCT. This study explores baseline liver elastography utility in predicting InO-related liver toxicity and SOS risk factors in adult ALL patients.

Data Highlights

Key Findings

• Baseline liver elastography showed 22% of patients had SWV suggestive of compensated advanced chronic liver disease (1.7–2.1 m/s), but none had clinically significant portal hypertension (>2.1 m/s).
• Only 2% of patients developed SOS during a median follow-up of 22.4 months, indicating low incidence with the amended InO dosing regimen.
• Grade ≥3 liver toxicities occurred in 10% of patients, all with baseline SWV <1.7 m/s, suggesting baseline elastography did not predict severe hepatic adverse events.
• Univariate analysis found no significant association between age, disease status, baseline bilirubin, ALT, or SWV group and risk of grade ≥3 liver toxicity.
• Most patients (98%) achieved complete remission or CR with incomplete count recovery with the combination therapy.

Clinical Implications

Baseline liver elastography may not reliably predict severe hepatic toxicity or SOS risk in patients receiving fractionated, reduced-dose InO combined with Mini-HyperCVD and blinatumomab. The low incidence of SOS observed supports the safety of the amended dosing regimen. Regular monitoring remains essential, but baseline SWV alone should not guide clinical decisions regarding hepatic risk in this setting.

Conclusion

In adults with B-cell ALL treated with reduced/fractionated InO regimens, baseline liver stiffness measured by elastography did not predict subsequent severe liver toxicity or SOS. These findings support the safety of current dosing strategies and highlight the need for continued vigilance in hepatic monitoring.

References

1. Kantarjian et al. 2016 -- Inotuzumab Ozogamicin in Relapsed/Refractory ALL
2. MD Anderson Cancer Center Clinical Trial NCT01371630 -- Mini-HyperCVD-InO-Blinatumomab Study
3. Ravaioli et al. 2021 -- Liver Elastography and Portal Hypertension in InO-treated ALL
4. INO-VATE Trial Long-term Follow-up -- Hepatic Toxicity and SOS Rates