As reported in the Journal of Clinical Oncology by Wieduwilt et al, findings in a cohort of the phase II Alliance study A041703 indicate that the chemotherapy-free regimen of inotuzumab ozogamicin followed by blinatumomab was highly active in patients aged ≥ 60 years with newly diagnosed B-cell acute lymphoblastic leukemia (ALL).
Study Details
In the U.S. multicenter study, 33 eligible patients enrolled between May 2019 and June 2021 with Philadelphia chromosome (Ph)–negative, CD22-positive, B-cell ALL received up to two cycles of inotuzumab ozogamicin followed by four or five cycles of blinatumomab with intrathecal methotrexate central nervous system prophylaxis. The primary outcome measure was 1-year event-free survival. On the basis of historical outcomes, the regimen would be deemed a failure for a 1-year event-free survival of ≤ 10% and a success for a 1-year event-free survival of ≥ 30%.
Key Findings
Patients had a median age of 71 years (range = 60–84 years) and median CD22 expression of 92% (range = 21%–100%). Eight patients (24%) had prior chemotherapy or radiation for other cancers, including six for multiple myeloma.
The composite complete remission rate was 85% after two cycles of inotuzumab ozogamicin and 97% at the end of two cycles of blinatumomab. At a median follow-up of 30 months, the 1-year event-free survival rate was 75% (95% confidence interval [CI] = 61%–92%), and the 1-year overall survival rate was 85% (95% CI = 73%–98%). Shorter event-free survival was associated with lower CD22 expression and detectable measurable residual disease at any time point.
Grade 3 or 4 adverse events occurring in ≥ 10% of patients were cytopenias and febrile neutropenia. Any-grade blinatumomab-related encephalopathy was reported in three patients (9%). Grade 3 tumor-lysis syndrome was reported in one patient (3%).
The investigators concluded: “Inotuzumab ozogamicin then blinatumomab without maintenance chemotherapy in older patients with untreated, Ph-negative, CD22-positive, B-cell ALL yields a high remission rate and excellent [event-free survival]. Given the lack of standard, safe, and effective therapies in this population, the regimen should be considered a standard treatment option.”
Matthew J. Wieduwilt, MD, PhD, of Wake Forest School of Medicine, Winston-Salem, North Carolina, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: Supported by grants from the National Cancer Institute and by Pfizer and Amgen. For full disclosure of all study authors, visit ascopubs.org.
