A 20-Year Review of Imatinib in Chronic Phase Chronic Myeloid Leukemia Patients after Failure with Interferon Therapy

INTRODUCTION The introduction of 20 years ago of imatinib, the first tyrosine kinase inhibitor (TKI), has drastically improved the survival of patients (pts) with Chronic Phase (CP) Chronic Myeloid Leukemia (CML), with a life expectancy similar to that of the general population. First used in patients after interferon (IFN) failure, imatinib and other TKIs have become standard frontline therapy. This analysis was done to investigate a 20-year outcome of Imatinib in pts Interferon-alpha failure. METHODS The long term outcome of 154 patients treated at our Institution with imatinib 400 mg after interferon failure from 1999-2000 was analyzed. RESULTS The median age was 44 (16 to 79yrs). 16 pts (11%) had prior malignancies 6 (38%) breast cancer, 3 (19%) skin cancer, 2 (12%) each prostate cancer and lymphoma, and 1 patient (6%) each lung cancer, colon cancer, and hairy cell leukemia. At the time of this analysis, 26 pts (17%) remained on imatinib of whom 22 pts (85%) had decreased their dosage. The median dose at last follow-up (FU) was 400mg (100-400mg). 128 pts (83%) discontinued imatinib permanently. Among them, 47 pts (37 %) changed to second generation TKIs, including 27 pts (58%) to dasatinib, 13 pts (28%) to nilotinib, and 7 (15%) to bosutinib.28 (60 %) received therapy with only 2 TKIs, and 19 (41%) received more than two TKIs. 81 pts (64%) did not receive a second TKI. Of these, 29 (36%) died, 23 (29%) were lost to follow up, 4 pts (12%) transformed to blast phase, 6 (8%) had stem cell transplant, 6 (8%) received farnesyltransferase inhibitor, 2 (3%) hyper-CVAD, 2 (3%) gemtuzumab ozogamicin, 1 (2%) homoharringtonine, 1(2%) with decitabine, and 7 (9%) had elective treatment discontinuation. All these 7 pts have remained treatment-free with a median follow up after discontinuation of 11.8 months. At baseline 13.6% had cardiac/vascular comorbidities and none had renal comorbidities. At 5-years, 8.4% had cardiac/vascular adverse events (AEs) and 1.2% had renal AEs. At last follow up, 13.4% had developed cardiac/vascular AEs and 3.8% renal AEs. 12 pts (8%) acquired second cancers after the start of imatinib. Of those, 2 pts each (16%) had esophageal, prostate, breast, and pancreatic cancers, and one each glioblastoma, basal cell cancer, lung cancer, and melanoma each had 1 patient (6%). At the time of this report, intention to treat (ITT) responses are available for 63 patients. The median FU for these pts was 232 months, with a median overall survival (OS)