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An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: Long-term results of the CMLALL1 trial

Citation

Lickliter, JD and Taylor, K and Szer, J and Grigg, A and Arthur, C and Hughes, TP and Durrant, S and Filshie, R and Irving, I and Seldon, M and Ellacott, J and Boyd, AW and D'Rozario, J and Rooney, K and Lynch, K and Bradstock, K, An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: Long-term results of the CMLALL1 trial, Leukemia and Lymphoma, 56, (3) pp. 630-638. ISSN 1042-8194 (2015) [Refereed Article]

DOI: doi:10.3109/10428194.2014.925547

Abstract

We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCRABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph+ ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCRABL targeting without compromising clinical outcomes.

Item Details

Item Type:Refereed Article
Keywords:Chemotherapeutic approaches; lymphoid leukemia; pharmacotherapeutics; signaling therapies
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Oncology and Carcinogenesis not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Rooney, K (Associate Professor Kim Rooney)
ID Code:119901
Year Published:2015
Web of Science® Times Cited:1
Deposited By:Medicine (Discipline)
Deposited On:2017-08-07
Last Modified:2017-08-07
Downloads:0

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