Background. Imatinib, a TKI inhibitor that revolutionized CML therapy, is now approaching ten years since its commercialization. Until now, even in complete durable molecular response, discontinuation of imatinib is not recommended, and imatinib remains a life-saving drug to be taken chronically. For this reason an important issue is represented by long-term side effects and among these the incidence of second malignancies. Roy et al. (Leukemia 2005) reported an unexpected incidence of second neoplasms in patients treated with imatinib after interferon (6/189 patients, 3.2%; urinary tract cancer: 4/6); in contrast, an analysis performed by Novartis in 9518 patients treated with imatinib all over the world did not provided evidence for an increased overall incidence of second malignancies (Leukemia 2006). However few data are available from independent studies, and particularly in imatinib-only treated patients. Aims. to evaluate the incidence of second malignancies in patients treated with imatinib frontline, enrolled in 3 multi-centre independent trials. Methods. overall, 559 patients have been enrolled in 3 concurrent clinical studies of the GIMEMA CML Working Party: CML/021, Imatinib 800 mg in intermediate Sokal risk patients (Clin Trials Gov. NCT00514488); CML/022, Imatinib 400 mg vs. 800 mg in high Sokal risk patients (Clin Trials Gov. NCT00510926); CML/023, observational, Imatinib 400 mg. The median age was 52 (extr.18 - 84) years; 308 patients (55%) were ≥50 years; the median follow-up is currently 54 months. Results. during the follow-up, 14 patients (2.5%) developed a second malignancy at a median distance of 16.5 months (range 2 - 52) from the start of imatinib therapy (Table 1); 4 of these tumors (2 colon cancer and 2 NHL) were diagnosed within 6 months. All patients were older than 50 years (median 64, extr. 53 - 77) at the diagnosis of the second malignancy. Eleven out of the 559 (2%) patients died due to second neoplasm progression. According to epidemiologic data (Registro Tumori) in Italy, the annual incidence of neoplasm varies from 1% in the range of age between 50 and 69 years and 3% for patients over 70 years. Conclusion. in this population of CML patients imatinib-treated, the incidence of second neoplasm do not differ from the observed incidence of neoplasm in the national population. In particular, in contrast to what previously reported, no increased incidence of urinary tract cancer was observed.
SECOND MALIGNANCIES IN 559 PATIENTS WITH CHRONIC MYELOID LEUKEMIA TREATED WITH IMATINIB FRONTLINE: DATA FROM THE GIMEMA CML WORKING PARTY
CAVAZZINI, Francesco;
2010
Abstract
Background. Imatinib, a TKI inhibitor that revolutionized CML therapy, is now approaching ten years since its commercialization. Until now, even in complete durable molecular response, discontinuation of imatinib is not recommended, and imatinib remains a life-saving drug to be taken chronically. For this reason an important issue is represented by long-term side effects and among these the incidence of second malignancies. Roy et al. (Leukemia 2005) reported an unexpected incidence of second neoplasms in patients treated with imatinib after interferon (6/189 patients, 3.2%; urinary tract cancer: 4/6); in contrast, an analysis performed by Novartis in 9518 patients treated with imatinib all over the world did not provided evidence for an increased overall incidence of second malignancies (Leukemia 2006). However few data are available from independent studies, and particularly in imatinib-only treated patients. Aims. to evaluate the incidence of second malignancies in patients treated with imatinib frontline, enrolled in 3 multi-centre independent trials. Methods. overall, 559 patients have been enrolled in 3 concurrent clinical studies of the GIMEMA CML Working Party: CML/021, Imatinib 800 mg in intermediate Sokal risk patients (Clin Trials Gov. NCT00514488); CML/022, Imatinib 400 mg vs. 800 mg in high Sokal risk patients (Clin Trials Gov. NCT00510926); CML/023, observational, Imatinib 400 mg. The median age was 52 (extr.18 - 84) years; 308 patients (55%) were ≥50 years; the median follow-up is currently 54 months. Results. during the follow-up, 14 patients (2.5%) developed a second malignancy at a median distance of 16.5 months (range 2 - 52) from the start of imatinib therapy (Table 1); 4 of these tumors (2 colon cancer and 2 NHL) were diagnosed within 6 months. All patients were older than 50 years (median 64, extr. 53 - 77) at the diagnosis of the second malignancy. Eleven out of the 559 (2%) patients died due to second neoplasm progression. According to epidemiologic data (Registro Tumori) in Italy, the annual incidence of neoplasm varies from 1% in the range of age between 50 and 69 years and 3% for patients over 70 years. Conclusion. in this population of CML patients imatinib-treated, the incidence of second neoplasm do not differ from the observed incidence of neoplasm in the national population. In particular, in contrast to what previously reported, no increased incidence of urinary tract cancer was observed.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
