Attempt to Discontinue Imatinib Following Interferon Alfa Pre-Treatment In Chronic Phase CML Patients Achieving Stable Complete Cytogentic Responses (CCyR)
Authors: Hardan Izhar , Volchek Yulia , Tohami Tali , Amariglio Ninette , Trakhtenbrot Luba , Koren-Michowitz Maya , Nagler Arnon 
Published: October 2019

Abstract
Abstract 4898
Imatinib (IM) has been shown to induce sustained clinical responses and stable remissions resulting in improved survival in chronic phase (CP) CML patients (pts.). Currently the state of the art is life long continuation of IM therapy which raises issues like the emergence of drug resistance, long-term safety and tolerability, compliance and costs. Interferon Alfa (IFNα), which has anti-CML activity and may induce major cytogenetic responses (MCyR), has in contrast to IM, immunoregulatory properties including the induction of anti-CML cytotoxic T-cell activity. Moreover, in initial studies of IM discontinuation it seemed that previous IFNα exposure was beneficial for the maintenance of molecular remission after IM cessation. We, therefore, hypothesized that adding IFNα to IM prior to IM discontinuation will increase the proportion of pts. remaining in continuous molecular response. We report on the long term, median follow up of 40 months (range, 33–41), outcome of CP CML pts. who discontinued IM after the addition of IFNα. CP CML pts. in CCyR for ≥2 years on IM were included. Study pts. received a combination of PegIFN (Pegasys, Roche) (180 μg/week, sc) and IM (400 mg) for 9 months followed by 3 months of PegIFN monotherapy, and were followed up thereafter without any anti leukemia therapy. Twelve CP CML pts. were included, 9 males and 3 females. Median age was 50.5 years (range, 33–67). Disease duration was 67 (18-96) months. Eight of the pts. (67%) received IFNα prior to IM as first line therapy. Eight of the patients had a major molecular response (MMR), 2 were in complete molecular response (CMR) (of 48 and 10 months duration) and 2 had less than a MMR. Of the evaluable pts. only 1 had a BCR ABL KD mutation (E373D). IFNα dose had to be reduce to 90–135 μg/week, sc due to intolerance in 10/12 pts. Median duration of CCyR (n=12) and MMR (n=8) at the time of IM discontinuation was 47.5 (21-86) months and 19.5 (9-84) months, respectively. Cytogenetic relapse occurred in 8 pts. 8 (2-38) months after IM discontinuation. Loss of molecular responses could be detected in all 8 pts. during follow up, and prior to the cytogenetic relapse at 8 (1-25) months post IM discontinuation. An additional 1 pt. had a molecular relapse but has maintained his CCyR 20 months post IM discontinuation. IM (400 mg/day) was reintroduced in all 8 pts. with loss of CCyR and they all re-achieved a CCyR 3.5 (3-7) months after IM re initiation. Five of the 8 pts. (62%) achieved also a MMR at 5, 7, 8, 10, and 11 months post IM re- administration, respectively. After a median follow up of 40 (range 33–41) months, 4 of the 12 study pts. (33.3%) are in persistent molecular remission. These 4 pts. achieved a CMR (n=1) (of 10 months duration) or MMR (n=3) (of 8, 14 and 19 months, respectively) prior to IM discontinuation. Notably, 2 of these 4 pts. had IFNα exposure as front line therapy pre-IM initiation. In summary, only a minority of CML pts. with stable MMR or CMR have a long lasting remission and will not relapse following IM discontinuation. Pts. having a cytogenetic relapse after IM discontinuation respond to IM re-administration by re-achieving CCyR and mostly MMR. The role of IFNα pre treatment, as well as the depth of molecular response needed to be achieved pre-IM discontinuation, should be further evaluated in a well designed 2 arms controlled randomized studies.

Disclosures:
No relevant conflicts of interest to declare.