Impact of inotuzumab ozogamicin prior to allo-HSCT in adult patients with R/R B-ALL

Adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) have a poor prognosis and a low long-term survival rate of 10%. Inotuzumab ozogamicin (InO) has achieved deep remissions and measurable residual disease (MRD) negativity in patients with R/R B-ALL in the phase III INO-VATE trial (NCT01564784); however, remissions are not durable, necessitating further consolidation approaches, such as allogeneic hematopoietic stem cell transplantation (allo-HSCT) which increases the risk of sinusoidal obstruction syndrome (SOS).

Here, we summarize a retrospective study published by Kayser et al.¹ in Haematologica on the impact of InO prior to allo-HSCT in patients with R/R B-ALL, with a focus on risk for SOS.

Study methods¹

• Included patients with R/R B-ALL, aged 16−69 years, who were treated with InO between 2016 and 2022, and subsequently received allo-HSCT.

Key findings¹

• A total of 58 patients were evaluated
• The complete remission rate prior to allo-HSCT was 84%.
• Among MRD evaluable patients (n = 44), MRD negativity was achieved in 59%.
• At a median follow-up of 30.5 months, the median overall survival was 11.2 months.
• The 1-year and 2-year overall survival rates were 50% and 36.7%, respectively.
• Overall, progressive disease was reported in 20 patients, which resulted in 15 deaths. The remaining five patients are still alive.
• The cumulative incidence of relapse and death was 35.0% and 37.6%, respectively.
• The post-allo-HSCT SOS was reported in 17 patients. Nine patients died due to SOS and multi-organ failure.
• Multivariate analyses showed that double alkylators (p = 0.038), allo-HSCT during first-line therapy (p = 0.050), and in trend allo-HSCT ≤60 days from the last InO application (p = 0.07) were significantly associated with an increased risk for SOS.

Key learnings

Results show that InO is an effective approach with successful bridge-to-transplant in patients with R/R B-ALL. InO showed a high risk of SOS; therefore, careful monitoring, and identification of associated risk factors, such as double alkylating conditioning regimens prior to allo-HSCT are needed to mitigate these risks.