Short Chemotherapy-Phased Imatinib (IM) Pulses Improve Long-Term Outcome of Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL).
Authors: Bassan Renato , Rossi Giuseppe , Pogliani Enrico Maria , Di Bona Eros , Angelucci Emanuele , Cavattoni Irene , Cortelezzi Agostino , Gianfaldoni Giacomo , Levis Alessandro , Ciceri Fabio , Mattei Daniele , Borlenghi Erika , Terruzzi Elisabetta , Borghero Carlo , Romani Claudio , Spinelli Orietta , Tosi Manuela , Oldani Elena , Intermesoli Tamara , Rambaldi Alessandro 
Published: October 2019

Abstract
Abstract 2029
Poster Board II-6
In a prospective NILG (Northern Italy Leukemia Group) study, short IM pulses were added to chemotherapy in order to 1) reduce incidence of early failures, 2) obtain higher transfer rates to stem cell transplantation (SCT), and 3) improve survival in comparison with a prior patient cohort treated with the same chemotherapy program without IM. IM 600 mg/d was given orally for 7 consecutive dd. with each chemotherapy block, starting from day 15 of induction (IDR/VCR/PDN±ASP) and day –3 of the following consolidation courses (5x IDR/VCR/CY/DEXA; 2x HD-MTX/ARA-C). All pts. received CNS chemoradioprophylaxis and were eligible to allogeneic SCT, or alternatively to HD therapy with autologous SCT and long-term maintenance with 6MP/MTX and intermittent IM. Between April '00 and November '08, 100 out of 404 pts. registered in NILG study 09/00 had Ph+ ALL (Ph chromosome and/or BCR-ABL rearrangement). M/F ratio was 1.17 and median age 46 years (range 19-66). 35 pts. constituted the control cohort (IM-) while, starting December '02, 59 pts. were included in the modified protocol (IM+), and 6 were excluded from analysis because treated on a continuous IM schedule. Of 59 IM+ pts., 53 received IM during induction/consolidation as planned and 6 during consolidation only (included in IM- group for remission induction analysis). Outcome to induction therapy of IM+ vs. IM- group was: CR 49/53 (92%) vs. 33/41 (80%), NR 2 (3.7%) vs. 5 (12%), ED 2 (3.7%) vs. 3 (7%) (P=NS). With a median observation interval from diagnosis of 5 years (range 0.6-9.2 years), 21 IM+ vs. 6 IM- pts. are alive in remission (CR1 pts.: 43% vs. 18%, P=0.02), and both OS (Figure) and DFS (0.39 vs. 0.21, P=0.044) rates at 5 years are significantly improved in IM+ group, especially when IM was administered from the induction cycle. The ability to perform a SCT increased from 53%(n=15: 11 allogeneic, 4 autologous) to 68%(n=37: 22 allogeneic, 5 autologous), partly owing to lower incidence of early relapse (26% vs. 56% at 1 year, P=0.005). SCT-related mortality was not different (P=0.58) and postgraft survival probability at 5 years was 0.45 overall, again with no difference related to SCT source or IM. Use of IM was not associated with greater reduction of BCR-ABL transcripts: by PCR analysis of BM samples taken at weeks 10, 16 and 22 in pretransplantation pts., a major response (absent/<10-4 PCR signals) was documented in 13/27 (48%) determinations from 13 evaluable IM- pts. vs. 16/49 (33%) from 25 IM+ pts.(P=NS). The short IM schedule used in this multicentric study demonstrated synergy with chemotherapy, resulting for the first time in NILG studies in improved long-term survival for this adverse subset. Problems of SCT-related toxicity and postgraft relapse need to be addressed further, to confirm curability of Ph+ ALL in a greater proportion of cases.

Disclosures:
No relevant conflicts of interest to declare.