S117: CHEMOTHERAPY-FREE TREATMENT WITH INOTUZUMAB OZOGAMICIN AND BLINATUMOMAB FOR OLDER ADULTS WITH NEWLY-DIAGNOSED, PH-NEGATIVE, CD22-POSITIVE, B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: ALLIANCE A041703

Abstract

Background: Older adult patients (pts) with Philadelphia-chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) have poor survival with chemotherapy. The anti-CD22 antibody-drug conjugate inotuzumab ozogamicin (InO) and anti-CD19/CD3 T-cell engager blinatumomab (blina) were each superior to conventional chemotherapy in Phase III studies in relapsed/refractory B-ALL. Because InO induces high CR rates and blina can induce durable remissions in low burden disease, we conducted a Phase II trial of induction InO then blina for older adults with newly-diagnosed (ND), Ph-, B-lineage ALL. Aims: The primary aim was to estimate the 1-year(yr) event-free survival (EFS) in older patients with ND, Ph-, B-lineage ALL treated with sequential InO induction then blina consolidation. Methods: Eligible were pts ≥60 years old with ND, Ph-, CD22+ (≥20% of lymphoblasts) B-lineage ALL without plan for allogeneic HCT (alloHCT) at registration. Pts with CNS leukemia or liver disease were excluded. Induction IA was InO 0.8 mg/m2 day(d) 1, 0.5 mg/m2 d8, d15 IV on a 21d cycle. Pts with adequate cytoreduction (marrow blasts reduced by ≥50% or cellularity ≤20%) after IA went to IB if in CR/CRi (InO 0.5 mg/m2 d1, d8, d15 IV; 28d cycle) or IC if not in CR/CRi (InO 0.8 mg/m2 d1, d8, d15 IV; 28d cycle). Those without cytoreduction to IA proceeded directly to Course II blina. Pts without events in Induction IA/B/C received Course II blina CIV (9 mcg/d x 7d then 28 mcg/d x 21d; 14d break; 28 mcg/d x28d). Pts with CR/CRi to InO received 2 more 28d cycles of blina, others received 3 more. CNS prophylaxis was methotrexate 15 mg intrathecal x 8 doses. No maintenance was given. The primary endpoint was 1-yr EFS with a lower limit of a 90% CI for 1-yr EFS >10% defined as success. EFS was the time from therapy start to failure to achieve CR/CRh/CRi by end course II, progression on therapy prior to end course II, relapse, or death, whichever occurred first. Results: Thirty-three eligible pts were treated (1 ineligible due to 2nd active malignancy). The median age was 71 years (range 60-84). Median WBC count was 3,200/mcl (range 6-38,000). Median CD22 expression was 92% (range 21-100%). Eight pts had therapy-related ALL. The cumulative CR rates through Induction IA/B/C and Course II were 85% and 97%, respectively (Table). With median follow up of 22 mo, the 1-yr EFS was 75% (95% CI 61-92%). The 2-sided 90% CI was 63-89% for 1-yr EFS with lower bound above 10% indicating regimen success. Twelve pts had events: 9 relapses, 2 deaths in remission (1 during blina, 1 after alloHCT), and 1 death without remission from respiratory failure with reported sinusoidal occlusion syndrome of liver. The 1-yr OS was 84% (95% CI 72-98%). Nine pts have died, 6 after relapse. Common Grade 3+ adverse events occurring in >10% of pts were neutropenia (88%), thrombocytopenia (73%), anemia (42%), leukopenia (39%), lymphopenia (27%), febrile neutropenia (21%), and encephalopathy (12%). Summary/Conclusion: InO induction then blinatumomab consolidation is highly active, tolerable therapy for ND, Ph-, CD22+ B-lineage ALL with durable remissions in the majority of pts. The regimen may be considered for older adults with ND, Ph-, CD22+ B-lineage ALL and a comparator regimen for future studies. Support: U10CA180821, U10CA180882, U10CA180820 https://acknowledgments.alliancefound.org. NCT03739814 - N=33 Induction InO I A/B/C Blinatumomab Course II Composite CR* 28 (85%) 32 (97%) CR 15 (45%) 19 (58%) CRh 11 (33%) 12 (36%) CRi 2 (6%) 1 (3%) Refractory 3 (9%)᛭ - Survival 1-yr EFS 75% (95% CI 61-92%) 1-yr OS 84% (95% CI 72-92%) *CR+CRh+CRi᛭ 1 completed IA only, 2 proceeded to course II Keywords: Acute lymphoblastic leukemia, Targeted therapy, B cell acute lymphoblastic leukemia, ALL