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.
Authors: Wieduwilt Matthew Joseph , Yin Jun , Kour Oudom , Teske Rebecca , Stock Wendy , Byrd Kenneth , Doucette Kimberley , Mangan James , Masters Gregory A. , Mims Alice S. , Jamieson Katarzyna , Dinner Shira Naomi , Bseiso Ali W. , Uy Geoffrey L. , Erba Harry Paul , Litzow Mark Robert , Stone Richard M. 
Published: June 2023

7006

Background:
Older adult patients (pts) with Philadelphia-chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) have poor survival with chemotherapy. The α-CD22 Ab-drug conjugate inotuzumab ozogamicin (InO) and α-CD19/CD3 T-cell engager blinatumomab (blina) were each superior to 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-ALL.
Methods:
Eligible were pts ≥60 years old with ND, Ph-, CD22+ (≥20% of blasts) B-ALL without plan for allogeneic HCT (alloHCT). Pts with CNS leukemia or liver disease were excluded. Induction IA was InO 0.8 mg/m
2
day (d) 1, 0.5 mg/m
2
d8, d15 IV on a 21d cycle. Pts with adequate cytoreduction (marrow blasts by ≥50% or cellularity ≤20%) after IA went to IB if in CR/CRi (InO 0.5 mg/m
2
d1, d8, d15 IV; 28d cycle) or IC if no CR/CRi (InO 0.8 mg/m
2
on d1 and 0.5 mg/m
2
on d8 and d15 IV; 28d cycle). Those without cytoreduction to IA started course II blina. Pts without events in 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. The primary endpoint was 1-yr event-free survival (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, relapse, or death, whichever occurred first.
Results:
Thirty-three eligible pts were treated (1 ineligible, 2
nd
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 Course 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 after alloHCT), and 1 death without remission from respiratory failure with sinusoidal occlusion syndrome of liver. The 1-yr OS was 84% (95% CI 72-98%). Nine pts have died, 6 after relapse.
Conclusions:
InO induction then blina consolidation is highly active for ND, Ph-, CD22+ B-ALL. The regimen is an option for older adults and a comparator regimen for future studies. Support: U10CA180821, U10CA180882, U10CA180820
https://acknowledgments.alliancefound.org
.
Clinical trial information: NCT03739814
.

N=33
I A/B/C
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%)
†

-

1-yr EFS
75% (95% CI 61-92%)

1-yr OS
84% (95% CI 72-92%)

*CR+CRh+CRi † 1 completed IA only