In a German phase II trial (INITIAL-1) reported in the Journal of Clinical Oncology, Matthias Stelljes, MD, and colleagues found that inotuzumab ozogamicin–based induction therapy followed by age-adapted chemotherapy was associated with promising outcomes in newly diagnosed patients older than age 55 with Philadelphia chromosome–negative B-cell–precursor acute lymphoblastic leukemia (ALL).
Matthias Stelljes, MD
Study Details
In the multicenter trial, 43 evaluable patients aged > 55 years with newly diagnosed, CD22-positive, BCR::ABL-negative B-precursor ALL were enrolled between June 2018 and April 2021. Patients received up to three cycles of inotuzumab ozogamicin–based induction. Patients with complete remission/complete remission with incomplete hematologic recovery could receive up to six cycles of age-adapted German Multicenter Study Group for Adult ALL consolidation and maintenance therapy.
The inotuzumab ozogamicin–based induction cycles consisted of :
- A 21-day cycle with inotuzumab ozogamicin at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15 in combination with dexamethasone at 10 mg/m2 per day on days 7 and 8 and 14 to 17, and one intrathecal injection of methotrexate at 12 mg, cytarabine at 40 mg, and dexamethasone at 4 mg
- Two 28-day cycles of inotuzumab ozogamicin at 0.5 mg/m2 on days 1, 8, and 15, plus intrathecal injection of methotrexate, cytarabine, and dexamethasone.
Key Findings
All 43 evaluable patients achieved complete remission/complete remission with incomplete hematologic recovery after one cycle (n = 38) or two cycles (n = 5) of inotuzumab ozogamicin–based induction. No measurable residual disease (10-4 threshold) was found in 23 patients (53%) after the second induction cycle and in 30 (71%) after the third cycle.
Event-free survival was 88% (95% confidence interval [CI] = 79%–98%) at 1 year and 55% (95% CI = 40%–71%) at 3 years. Overall survival was 91% (95% CI = 82%–99%) at 1 year and 73% (95% CI = 59%–87%) at 3 years. No patients died within 6 months after the start of induction.
The most common grade ≥ 3 adverse events during induction were leukopenia (74%, 19%, and 2% in cycles 1, 2, and 3, respectively), neutropenia (56%, 14%, and 0%), thrombocytopenia (49%, 7%, and 2%), anemia (37%, 5%, and 0%), and elevated liver enzymes (eg, alanine aminotransferase in 14%, 5%, and 0%).
The investigators concluded, “Inotuzumab ozogamicin–based induction followed by age-adapted chemotherapy was well tolerated and resulted in high rates of remission and overall survival. These data provide a rationale for integrating inotuzumab ozogamicin into first-line regimens for older patients with B-ALL.”
Dr. Stelljes, of University Hospital Münster, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pfizer Inc. For full disclosures of the study authors, visit ascopubs.org.
