Effective De-Escalation of B-Cell ALL Induction Therapy

The anti-CD22 antibody-drug conjugate inotuzumab ozogamicin (InO) provides high response rates in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). To explore its efficacy and safety in the frontline setting, investigators in Germany conducted an industry-supported prospective, multicenter, phase 2 trial in 45 patients older than 55 years with newly diagnosed Philadelphia chromosome–negative, CD22-expressing precursor-B-cell ALL.

Induction therapy included 2 or 3 cycles of InO plus dexamethasone, followed by age-adapted consolidation (5 cycles), late intensification (1 cycle), and maintenance chemotherapy (up to 2 years). Intrathecal chemotherapy prophylaxis was administered during all treatment phases. Serial measurable residual disease (MRD) testing was performed by flow cytometry (minimum sensitivity, 1 in 10⁴ cells).

The 43 evaluable patients had a median age of 64 (range, 56–80); 3 had central nervous system involvement at diagnosis, and 12 had high-risk cytogenetic alterations. All patients achieved complete remission (CR) or CR with incomplete peripheral blood count recovery; 53% were MRD negative after two InO cycles, 71% after 3 cycles. With a median follow-up of 2.7 years, 1-year event-free survival (EFS; the primary study endpoint) was 88% and 3-year EFS was 55%. Toxicities during InO cycles occurred mostly in cycle 1 and included cytopenias (58%–74%; most grade 3–4), elevated bilirubin (21%, grade 3–4 in 2%), and elevated transaminases (37%, grade 3–4 in 14%). One patient developed hepatic veno-occlusive disease during cycle 2 of InO induction.