In a phase II trial (EWALL-INO) reported in the Journal of Clinical Oncology, Chevallier et al found that inotuzumab ozogamicin combined with low-dose chemotherapy was active in the first-line treatment of older patients with newly diagnosed CD22-positive Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (ALL).
Study Details
In the trial, 131 evaluable patients (aged ≥ 55 years) from 30 sites in France, 2 in the Czech Republic, and 1 in Finland were enrolled between December 2017 and March 2022. After a prephase of corticoid steroid treatment, patients received a first induction consisting of vincristine, dexamethasone, and three injections of inotuzumab ozogamicin (0.8 mg/m2 on day 1, 0.5 mg/m2 on days 8 and 15) followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of inotuzumab ozogamicin (0.5 mg/m2 on days 1 and 8).
Responders 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 was 1-year overall survival. The null hypothesis was a 1-year overall survival up to 60%.
Key Findings
A total of three patients died during induction 1 (two from multiple organ failure and one from hemorrhage); none died during induction 2. After induction 2, 90% of patients achieved complete remission or complete remission with incomplete platelet recovery, with 80% having measurable residual disease (MRD2) < 10–4.
Among 119 responders, 47 had disease relapse, and 14 died in complete remission or complete remission with incomplete platelet recovery. Median follow-up for surviving patients was 31.3 months (interquartile range = 20.2–37.7 months).
Overall survival at 1 year was 73%; the 2-year rate was 55%. 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%.
High-risk cytogenetics was associated with poorer overall survival (hazard ratio [HR] = 2.90, P < .001), poorer relapse-free survival (HR = 3.23, P < .001), and 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 higher risk of relapse (subdistribution HR = 3.82, P = .004).
A total of 184 grade 3, 40 grade 4, and 5 grade 5 adverse events were reported. Among grade 3 or 4 adverse events, 7% occurred during the prephase, 41% during induction 1, 8% during induction 2, 28% during consolidations, 11% during maintenance, and 5% after the last administration of treatment.
The investigators concluded: “Our results support [inotuzumab ozogamicin’s] use in first-line regimens for older patients with CD22[-positive] Ph[-negative] [B-cell precursor] ALL.”
Patrice Chevallier, MD, PhD, of the Hematology Department, Nantes University Hospital, Nantes, France, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pfizer. For full disclosures of the study authors, visit ascopubs.org.
