Efficacy and Safety of Imatinib Treatment in Elederly Patients with Chronic Myeloid Leukemia.
Authors: Martino Bruno , Vincelli Iolanda , Ronco Francesca , Modafferi Bruno , Princi Domenica , Morabito Fortunato , Izzo Barbara , Pane Fabrizio , Nobile Francesco 
Published: October 2019

Abstract
The increase of median survival of the general population results in a higher incidence of Chronic Myeloid Leukemia (CML) in the elderly. In our series of 260 cases from a single institution the mean age of CML cases was 52.5 from 1977 to 1987 and 61.9 from 1999 to 2003; in other words, in the last 5 years 39.6% of our CML cases was over 70 years of age. The introduction of Imatinib (STI) has changed the treatment strategy in CML elderly patients, previously treated with hydroxyurea (HU). Efficacy, tolerability and cost of STI therapy in this CML setting are worth to be considered. For this purpose we retrospectively evaluated our elderly CML patients treated with STI. Our series consists in 24 cases, M/F 18/6, with a median age at diagnosis of 70.1 yrs (60–83), and 73.4 (65–83) at time of STI therapy; Co-morbidity included hypertension (5 cases), renal failure (2), cardiovascular diseases (4), diabetis (1), psoriasis (1), B-cell chronic lymphocytic leukaemia (B-CLL) (1).
The mean interval from diagnosis to STI was 2.6 yrs (0-7). Sokal index was low in 4 cases, intermediate in 18, high in 2; Euro index was low in 15, intermediate in 7, high in 2. All cases were bcr/abl positive (p210), 19 Ph1+, 4 Ph1-. Four patients, one in AP, were untreated. Six cases had received HU, 3 in accelerate phase (AP). Out of 14 cases previously treated with interferon (IFN) for 1 to 43 months, 5 patients were intolerant, 7 resistant (1 in AP), while 2 patients obtained haematological and cytogenetic complete response and received IFN treatment for 24 and 29 months, respectively. STI was administered at 400 mg/day in CP and 600 mg/day in AP, for a mean period of 2 yrs (1 to 46 months). All cases but 3, 2 in AP and 1 in chronic phase (CP), either obtained or maintained the hematological response. After 6 to 12 months of STI therapy, out of 24 cases, 11 obtained complete cytogenetic (CG) response (1 case in AP), 1 minor, 3 no CG response; in the remaining cases CG response was not evaluable, in 2 cases because CG response was already obtained after IFN therapy, in 3 because of short period of therapy, and in 4 because Ph1 negative at onset. Quantitative molecular response, evaluated in 9 out of 11 patients achieving CG response, was obtained in 8 cases; notably, in 4 cases bcr/abl was so low to become undetectable. Tolerability was generally good in all but 2 cases, requiring STI permanent withdrawal; one patient presented subdural hemorrage needing surgery, the other one presented hepatic failure The remaining toxicity consisted of grade 3 cough, scrotal oedema, reversible lethargy because of cerebral oedema; and fatigue requiring temporary withdrawal or dose reduction in 7 patients. Also hematological toxicity required temporary drug withdrawal 2 cases. Out of 4 patients requiring permanent dose reduction to 300 mg/day, 3 are maintaining CG and molecular response, while one patients lost CG response. In detail, out of 5 cases in AP, 3 died of progressive disease, one maintains haematological and the last CG complete response. Interestingly the patients affected by psoriasis demonstrated a clear improvement of skin lesions and the patient with concomitant B-CLL achieved a response at phenotypic level.
At the time of the present report 3 patients died, all in AP because of disease progression. According to the present data STI therapy is indicated in CML elderly patients.