Final results of CA180-372/COG AALL1122 phase 2 trial of dasatinib and chemotherapy in pediatric patients with newly-diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (PH plus ALL)
Hunger, S. Saha, Vaskar Devidas, M. Valsecchi, M. Gastier-Foster, J. Cazzaniga, G. Reshmi, S. Borowitz, M. Moorman, A. Heerema, N.
Hunger, S.
Saha, Vaskar
Devidas, M.
Valsecchi, M.
Gastier-Foster, J.
Cazzaniga, G.
Reshmi, S.
Borowitz, M.
Moorman, A.
Heerema, N.
Citations
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Abstract
Background and Aims: We administered EsPhALL chemotherapy plus
dasatinib 60 mg/m 2 (starting day 15) at COG (North America and Aus-
tralia) and EsPhALL (Italy and UK) sites. Patients (>1-17.99 years)
with MRD 0.05% following induction Ib or MRD-positive follow-
ing three additional high-risk (HR) chemotherapy blocks were allo-
cated to CR1 HSCT. The remaining patients received chemother-
apy plus dasatinib for 2 years. Only CNS3 patients received cranial
irradiation.
Methods: Enrollment was 109 patients (3/2012-5/2014); 3 were ineli-
gible and received no trial therapy.
Results: All 106 treated-patients achieved CR. With database lock
6/29/19, 48/106 had events including 38 relapses (24 marrow, 4
CNS, 4 marrow+CNS, 4 other, 2 marrow+other), 9 treatment-related
deaths (7 in chemotherapy-assigned patients, 2 post-HSCT), and one
malignancy. Nineteen (17.9%) patients met HSCT criteria, 15 (14.2%)
received CR1 HSCT with 9 remaining event-free, 2 transplant-related
deaths (6 weeks, 7 months), and 4 relapses (3 alive, 1 died). Among
the four not transplanted, 2 were event-free, 1 relapsed and died, and
1 had an astrocytoma. The remaining 87 patients were assigned to
chemotherapy plus dasatinib, with 47 remaining event-free. Seven died
in CR1, 5 on-therapy (3 in HR3, 1 reinduction 2, 1 continuation) and 2
post-therapy (21 and 31 months). Thirty-three relapsed, 3 on-therapy
at 16-23 months (all alive) and 30 post-therapy (18 12 months, 12
>12 months; 22 alive and 8 deceased). The primary toxicities were
febrile neutropenia and infection; one chemotherapy patient discon-
tinued dasatinib (allergy) and one discontinued post-HSCT (myelosup-
pression).
Conclusions: Dasatinib plus EsPhALL chemotherapy is safe and effec-
tive in pediatric Ph
+ALL. With only 14% of patients undergoing CR1 HSCT, as compared to 81% in the EsPhALL 2004 and 38% in the
EsPhALL2010 imatinib trials, this trial demonstrates similar outcomes
with 5-year EFS 54.6% (95% CI, 44.5-63.6) and OS 81.7% (95% CI,
82.8-87.9) versus 60.3%/71.5% in EsPhALL 2004, and 57%/71.8% in
EsPhALL 2010
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Hunger S, Saha V, Devidas M, Valsecchi M, Gastier-Foster J, Cazzaniga G, et al. Final results of CA180-372/COG AALL1122 phase 2 trial of dasatinib and chemotherapy in pediatric patients with newly-diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (PH plus ALL). Pediatric Blood & Cancer. 2020;67:S15-S6