In a phase II trial (EWALL-INO) published in the Journal of Clinical Oncology, researchers found that inotuzumab ozogamicin combined with low-dose chemotherapy showed promising activity in the first-line treatment of older patients with newly diagnosed CD22-positive Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (ALL). The study, led by Patrice Chevallier, MD, PhD, suggests a potential new approach for treating this challenging patient population.
The trial enrolled 131 evaluable patients aged 55 years or older across multiple sites in France, the Czech Republic, and Finland between December 2017 and March 2022. Following a prephase of corticoid steroid treatment, patients received induction therapy consisting of vincristine, dexamethasone, and inotuzumab ozogamicin. Responders then received up to six cycles of chemotherapy consolidation and 18 months of chemotherapy maintenance. Allogeneic transplantation was permitted after three consolidation cycles.
The primary endpoint of the study was 1-year overall survival. The null hypothesis was a 1-year overall survival up to 60%.
Efficacy Outcomes
The study reported that 90% of patients achieved complete remission or complete remission with incomplete platelet recovery after induction 2, with 80% having measurable residual disease (MRD2) < 10–4. Overall survival at 1 year was 73%, and the 2-year rate was 55%. The estimated median overall survival was 33.7 months. The 1-year rate of relapse-free survival was 66%, and the cumulative incidence of relapse was 25%. Median event-free survival was 20.6 months, with 1- and 2-year rates of 64% and 46%. Among 10 patients undergoing allogeneic transplantation, rates of 1- and 2-year overall survival and relapse-free survival were all 90%.
Prognostic Factors
High-risk cytogenetics was associated with poorer overall survival (HR = 2.90, P < .001), poorer relapse-free survival (HR = 3.23, P < .001), and a higher risk of relapse (subdistribution HR = 4.09, P < .001). Higher CD22 expression (≥ 70%) was associated with improved overall survival (HR = 0.52, P = .03). MRD2 ≥ 10–4 was associated with poorer relapse-free survival (HR = 2.61, P = .02) and a higher risk of relapse (subdistribution HR = 3.82, P = .004).
Safety Profile
The trial reported 184 grade 3, 40 grade 4, and 5 grade 5 adverse events. The investigators concluded that the results support the use of inotuzumab ozogamicin in first-line regimens for older patients with CD22-positive Ph-negative B-cell precursor ALL.
