Nilotinib Combined With Multi-Agent Chemotherapy For Adult Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Final Results Of Prospective Multicenter Phase 2 Study

• Published in: Blood 2013-11, Vol.122 (21), p.55-55
• Main Authors: Kim, Dae-Young, Joo, Young Don, Kim, Sung-Doo, Lee, Jung-Hee, Lee, Je-Hwan, Kim, Dong-Hwan, Kim, Kihyun, Jung, Chul Won, Kim, Inho, Yoon, Sung-Soo, Park, Seonyang, Ahn, Jae-Sook, Yang, Deok-Hwan, Lee, Je-Jung, Kim, Yang Soo, Mun, Yeung-Chul, Kim, Hawk, Moon, Joon Ho, Sohn, Sang Kyun, Lee, Won Sik, Won, Jong-Ho, Hyun, Myoung Soo, Park, Jinny, Lee, Jae Hoon, Shin, Ho-Jin, Eom, Hyeon Seok, Lee, Gyeong Won, Lim, Sung-Nam, Kim, Young Jin, Cho, Young-Uk, Chi, Hyun-Sook, Lee, Kyoo-Hyung
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.55.55

We previously reported the interim analysis on the clinical outcome of nilotinib (Tasigna®, Novartis Pharma, Basel, Switzerland), when combined with multi-agent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) in adults. Herein, we reported the final results of the multicenter prospective phase2 trial of Adult Acute Lymphoblastic Leukemia Working Party, the Korean Society of Hematology. Newly diagnosed Ph+ALL patients aged 18 years old or more were eligible when they had adequate organ function. Diagnosis of Ph+ALL was performed via confirmation of the presence of Ph chromosome by conventional GTL-band technique, and/or positive molecular analysis with nested RT PCR for detection of BCR-ABL fusion transcripts. Written informed consent was obtained from all subjects. All patients received induction treatment consisting of vincristine, daunorubicin, oral or parenteral prednisolone, and nilotinib. After achieving complete remission (CR), subjects received either 5 courses of consolidation followed by 2-year maintenance with nilotinib, or allogeneic hematopoietic cell transplantation (alloHCT) depending on the donor availability, his/her tolerability, and patient's wish. Nilotinib was administered twice a day with a single dose of 400mg (800mg per day) from day8 of induction until the initiation of conditioning for alloHCT or the end of maintenance therapy. Minimal residual disease (MRD) monitoring was performed at the central lab with quantitative RT-PCR assays for peripheral blood BCR-ABL RNA using LightCycler® Technology in serial; at the time of diagnosis, at hematologic CR(HCR), and every 3 months thereafter. BCR-ABL quantification was expressed relative to the amount of glucose-6-phosphate dehydrogenase (G6PDH) mRNA. The molecular response was defined as complete (MCR, MRD-negative) if the BCR-ABL/G6PDH ratio was less than 1x10-6. Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (version 2.0). Subjects had been followed up for 2 years after alloHCT or during maintenance therapy. Data were frozen up in June, 2013. A total of 91 subjects (male: female = 45: 46) were enrolled onto the study between January 2009 and May 2012. The median age was 47 (range 18-71) years old. Type of BCR breakpoint was minor (e1a2) in 71% of patients. The median BCR-ABL/G6PDH ratio was 6.09 (bone marrow) and 3.28 (peripheral blood) at diagnosis. During induction, all subjects required blood product tr