BESPONSA (inotuzumab ozogamicin) is approved for use in both adult and pediatric patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). To lower the risk of hepatic sinusoidal obstruction syndrome (SOS), it is recommended to limit inotuzumab ozogamicin treatment to no more than two cycles before hematopoietic stem cell transplantation (HSCT), based on findings from the Phase III inotuzumab ozogamicin -VATE trial.

The data analysis evaluated 338 adult R/R B-ALL patients, divided into two groups based on total cumulative inotuzumab ozogamicin dose: those receiving ≤3.3 mg/m² (n = 161; median dose 2.09) and those receiving >3.3 mg/m² (n = 177; median dose 4.98). Baseline characteristics were largely comparable between groups. HSCT was performed in 42.2% of the lower-dose group and 42.4% of the higher-dose group. Complete remission or remission with incomplete blood count recovery (CR/CRi) was significantly higher in the >3.3 mg/m² group (90.4%) compared to the ≤3.3 mg/m² group (50.9%), with both groups achieving remission within roughly 0.8 months.

Further analysis of patients who responded after the first treatment cycle showed HSCT rates of 74% in the lower-dose group versus 46% in the higher-dose group. Median progression-free survival (PFS) and overall survival (OS) among these early responders were 6.5 and 12.2 months for the ≤3.3 mg/m² group, vs. 6.1 and 9.2 months for the >3.3 mg/m² group, respectively.

Disease progression remained the most common cause of death in both groups, accounting for 37% and 42% of deaths in the lower- and higher-dose groups, respectively. Grade ≥3 adverse events (AEs) were more frequent with higher dosing (79.7% vs. 59.6%), as were treatment discontinuations due to AEs (19.2% vs. 14.9%). Higher-grade hematologic and liver-related toxicities were more common in the >3.3 mg/m² group, though serious AEs occurred in a similar proportion of patients in both groups (59%).

Post-HSCT SOS (any grade) occurred in 21% of the lower-dose group and 23% of the higher-dose group, with Grade 3/4 SOS in 13% and 17% of patients, respectively. Post-transplant mortality was 52% overall, with non-relapse mortality (NRM) at 38%. Among early responders, post-HSCT mortality was 39% in the ≤3.3 mg/m² group and 62% in the >3.3 mg/m² group, with corresponding NRM rates of 28% and 44%.

KOL insights

“Patients receiving lower doses of inotuzumab ozogamicin showed better tolerability with less myelosuppression and similar SOS risk compared to higher doses. Notably, survival outcomes favored the lower-dose group, though more patients proceeded to allo-HCT, influencing the results.” – Expert Opinion

Conclusion

The treatment landscape for B-cell acute lymphoblastic leukemia (B-ALL) has undergone a notable transformation with the introduction of targeted immunotherapies, leading to more personalized and stratified care. BESPONSA (inotuzumab ozogamicin), an antibody-drug conjugate targeting CD22, remains a key therapeutic option—particularly for patients who are older, heavily pretreated, or ineligible for stem cell transplant or CAR-T therapy. Its ability to induce high remission rates in relapsed or refractory settings makes it a practical and accessible choice, especially given its off-the-shelf availability. However, concerns around hepatotoxicity, particularly SOS post-transplant, underscore the need for careful dosing and patient selection.

In this evolving space, while some oncologists may increasingly favor CAR-T options like TECARTUS for appropriate adults, BESPONSA continues to hold value in real-world clinical practice—especially for patients who need prompt therapy or cannot access or tolerate cell-based treatments. As a result, the B-ALL treatment paradigm is becoming more nuanced, with ADCs like BESPONSA maintaining a strong foothold alongside newer, high-efficacy therapies, each serving distinct patient segments.