Abstract 5552: Extremely high rate of complete hematological response of elderly Ph+ acute lymphoblastic leukemia (ALL) patients by innovative sequential use of Nilotinib and Imatinib. A GIMEMA Protocol LAL 1408
Authors: Martinelli Giovanni , Papayannidis Cristina , Piciocchi Alfonso , Vitale Antonella , Iacobucci Ilaria , Soverini Simona , Raimondo Francesco D. , Paolini Stefania , Bonifacio Massimiliano , Carella Angelo Michele , Cazzola Mario , Cuneo Antonio , Leoni Pietro , Luppi Mario , Morra Enrica , Specchia Giorgina , Elia Loredana , Foà Robin , Baccarani Michele 
Published: May 2015

Abstract
Background: We have explored if the administration of two TKIs, Nilotinib (NIL) and Imatinib (IM) can improve the results without increasing the toxicity in the elderly Ph+ Acute Lymphoblastic Leukemia (ALL) patients. We investigate the type and number of BCR-ABL kinase domain mutations developing during and after the study.
Methods: We have designed a study (ClinicalTrials.gov. NCT01025505) in which patients more than 60 years old or unfit for intensive chemotherapy and SCT where treated with two TKIs, NIL 400 mg twice daily, and IM 300 mg twice daily, alternating for 6 weeks for a minimum of 24 weeks (study core) and indefinitely in case of response. The 6-weeks rotation schedule was respected, irrespectively of temporary discontinuations. The primary end-point was the rate of Disease Free Survival (DFS) at 24 weeks (4 courses of treatment); the secondary end points included the evaluation of CHR, CCgR and CMR rates.
Results: 39 patients have been enrolled in 15 Italian hematologic Centers (median age 66 years, range 28-84). Among these, 8 patients were unfit for standard chemotherapy or SCT (median age 50 years, range 28-59). 27 patients were p190, 5 were p210 and 7 were p190/p210. After 6 weeks of treatment, 36 patients were evaluable for response: 34 were in CHR (94%) and 2 in PHR (6%). 23 patients have already completed the study core (24 weeks), 87% were in CHR and 17 are currently continuing therapy in the protocol extension phase.
Thus, the OS at 1 year is 79%, and 64% at 2 years. Overall, 1 patient was primarily resistant and 13 patients have relapsed, with a median time to relapse of 7.6 months (range 0.8-16.1 months), for a DFS of 51.3% at 12 months. Conclusions: In this small cohort of Ph+ ALL elderly/unfit patients, the rates of relapse and progression were not likely to be different from the rates observed with Imatinib alone. Acknowledgements: ELN, AIL, AIRC, PRIN, FP7 NGS-PTL project.
Citation Format: Giovanni Martinelli, Cristina Papayannidis, Alfonso Piciocchi, Antonella Vitale, Ilaria Iacobucci, Simona Soverini, Francesco Di Raimondo, Stefania Paolini, Massimiliano Bonifacio, Angelo Michele Carella, Mario Cazzola, Antonio Cuneo, Pietro Leoni, Mario Luppi, Enrica Morra, Giorgina Specchia, Loredana Elia, Robin Foà, Michele Baccarani. Extremely high rate of complete hematological response of elderly Ph+ acute lymphoblastic leukemia (ALL) patients by innovative sequential use of Nilotinib and Imatinib. A GIMEMA Protocol LAL 1408. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5552. doi:10.1158/1538-7445.AM2014-5552