-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4256 Intermittent Imatinib Mesylate in Children with Chronic Myeloid Leukemia: Results and Outcome

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster III
Hematology Disease Topics & Pathways:
Diseases, Biological, CML, Therapies, Pediatric, Study Population, Myeloid Malignancies, TKI
Monday, December 3, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Francesco Malaspina, MD1*, Maria Caterina Putti, MD2*, Michelina Santopietro, MD1*, Saverio Ladogana, MD3*, Rosamaria Mura, MD4*, Roberta Burnelli, MD5*, Nadia Vacca, MD6*, Lorenzo Rizzo1*, Maria Luisa Moleti, MD1*, Anna Maria Testi, MD1*, Andrea Biondi7, Franco Locatelli8, Giuseppe Saglio9, Robin Foà, MD1 and Fiorina Giona, MD1

1Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy
2Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Padova, Padova, Italy
3Department of Pediatrics, "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
4Pediatric Hemato-Oncology Unit, Ospedale Regionale per le Microcitemie, Cagliari, Italy
5Pediatric Hemato-Oncology Unit, Sant'Anna Hospital, Ferrara, Italy
6Pediatric Unit, Ospedale di Sassari, Sassari, Italy
7University of Milano-Bicocca, Department of Pediatrics, San Gerardo Hospital/Fondazione MBBM, Tettamanti Research Center, Monza (MB), Italy
8Department of Hematology/Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
9Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy

Imatinib mesylate (IM) has demonstrated to be highly effective in children with chronic myeloid leukemia (CML). The main issues remain the long-term side effects in pre-pubertal children and the poor compliance in adolescents. The aims of this study were: a) to evaluate the feasibility and efficacy of IM given intermittently to molecular responder (MR) CML children in chronic phase (CP), b) to reduce the long-term side effects of MR patients (pts) who started IM in pre-pubertal age, c) to improve compliance of poorly compliant adolescents in major MR (MMR).

Among CP-CML pts aged <18 years at diagnosis treated with IM at a dose of 340 mg/m2/day and with a follow-up ≥36 months, those with a persistent MR4.5-MR5 or in MR with long-term side effects, and those in MMR who were poorly compliant to continuous IM, were considered eligible for an intermittent IM (int-IM) administration. The intermittent schedule consisted of IM administered at the same dose for 3 weeks monthly (3 weeks on, 1 week off). Quantitative molecular analysis of the BCR-ABL1 transcript levels was carried out monthly on peripheral blood and every 3 months on bone marrow, along with cytogenetics. Long-term side effects (bone and mineral metabolism, growth rate and pubertal development) were regularly monitored. Re-treatment with IM given continuously or with other tyrosine kinase inhibitors (TKI) was planned if there was a loss of MMR in two consecutive samples or a cytogenetic relapse. IM discontinuation was considered for patients with a persistent MR4.5-MR5.

Fifteen of 58 CP-CML pts diagnosed between March 2001 and June 2015 received IM given intermittently for a median of 40 months(range: 14-86). Before starting int-IM, 5 pts had been in persistent MR4.5-MR5 for a median of 39 months (Group I), 4 pts had been in MR for a median of 28.5 months and had been suffering from long-term side effects (Group II), and 6 pts had been in MMR and were poorly compliant to treatment (Group III). Features and outcome of the 15 pts are shown in Table 1. Group I: 3/5 pts in MR4.5-MR5 discontinued int-IM after 16, 34 and 36 months and remain in continuous MR after 89, 90 and 107 months; 2 pts are still receiving int-IM for 14 and 36 months, respectively. Group II: 2/4 pts achieved a deeper MR (1 from MR4 to MR4.5 and 1 from MR4.5 to MR5) while on int-IM. However, 3 pts lost the response after 24 (cytogenetic relapse), 40 and 77 (molecular) months from the beginning of int-IM; all of them were successfully treated with IM given continuously. One pt is still receiving int-IM. Group III: 2/6 pts achieved a deeper MR (1 from MR3 to MR4.5 and 1 from MR3 to MR4) while on int-IM. However, 5/6 patients lost their response after a median time of 69 months (57-74). Four of them were treated with IM given continuously and 1 received dasatinib; all obtained a response. One, who achieved a deeper MR (MR3 to MR4), is still on int-IM after 86 months. Overall, 4/15 (26.7%) pts improved their molecular response while on int-IM and 3/15 pts (20%) successfully discontinued treatment. On the other hand, 8/15 pts (53.3%) failed int-IM after a median of 63 months (range 24-77) from the beginning (6 pts lost MMR and 2 pts had a cytogenetic relapse). No pt underwent a stem cell transplantation. Long-term side effects (bone metabolism, growth rate and pubertal development) progressively improved during IM given intermittently. At the last follow-up, 6 pts (4 MR5, 1 MR4.5, 1 MR3) are still receiving int-IM, 5 (3 MR4, 2 MR2) are receiving continuous IM, 3 (MR4.5-MR5) are treatment-free and 1 (MR3) is being treated with dasatinib. All patients are alive at a median time from diagnosis of 151 months (range 52-266).

Our experience suggests that an intermittent schedule of IM given 3 weeks a month could be an effective strategy before stopping IM in CP-CML children in persistent deep MR. Moreover, this approach is capable of improving the molecular response in poor compliant pts and is useful to reduce IM-related long-term side effects. The relatively high number of relapses in group III (5/6, 83%) is indicative of its poor efficacy in pts not compliant to IM given continuously. Based on these data, a prospective cooperative study has been planned.

Disclosures: Malaspina: Sapienza University, Rome: Other: Resident in Hematology. Rizzo: Sapienza University, Rome: Other: Resident in Hematology. Foà: CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; NOVARTIS: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau.

*signifies non-member of ASH