09:00–09:05Escalated Dasatinib Dose up to 60 Mg O.D. in Elderly Patients with Chronic Myeloid Leukemia in Late Chronic Phase Resistant to or Intolerant of Imatinib-12 Months Follow-up

Background: Dasatinib (SPRYCEL^®, formerly BMS-354825) is a novel, oral, multitargeted kinase inhibitor of BCR-ABL, SRC, and other kinases that is approximately 300 times more potent than Imatinib in vitro. Dasatinib has been shown to be effective and safe in pts with CML resistant or intolerant to Imatinib, As might be expected, older patients experienced more adverse events, both hematologic and non-hematologic with the standard dosage of 100 mg once daily. Data regarding tolerability in elderly pts are scanty The aim of this study is to test if escalated dasatinib dose up to 60 mg once daily is as effective as standard dose of 100 mg QD with a better toxicity profile in elderly patients with chronic myeloid leukemia in late chronic phase resistant to or intolerant of Imatinib.

Patients and Methods: As of July 2007, 4 eligible patients have been enrolled and treated :4F ; median age 77 y [range 73–82]; 1 imatinib-resistant, 3 imatinib-intolerant). Dasatinib was given at 20 mg once daily (QD) starting dose with dose escalation to 40 mg QD or 60 mg QD in pts tolerant or lacking response. Complete blood counts were obtained weekly for the first 12 weeks; bone marrow cytology and cytogenetics every 1 months, and molecular monitoring of BCR-ABL transcript levels by real-time qPCR every 12 weeks. The primary endpoint was toxicity. Median time from diagnosis of CML was 62 months (range 36 – 88). Prior therapy included interferon-alpha in 1/4. 50 percent of pts had 400 mg of prior imatinib. 25% had 600 mg. 100 % of pts received imatinib for >3 yrs. Best response to prior imatinib therapy was a CHR in 100, and partial (PCyR) cytogenetic responses in 75 % of pts. No BCR-ABL baseline mutations were found.

Results: The analyses with a median follow-up of 12 months (7–12) months show hematologic toxicity (grade 3 thrombocytopenia and leukopenia) at 60 mg OD in 2 out 4 pts. Dose interruptions occurred in 1/4 pts at 60 mg One pts was intolerant to dasatinib and switched to HU Patients received an average daily dose of 40 mg/day (range 20–60 mg). Non-hematologic toxicity consisted mainly of grade 1 diarrhea, headache 2 patients experienced grade II muscolo-skeletal toxicity and fatigue at 60 mg/day.) 100% pts had a CHR, and 50% a PCyR.

Conclusions: Dasatinib demonstrated substantial hematologic activity in elderly patients with late CP-CML. Despite the maximum dose reached was 60 mg QD only the 75% of pts were able to continued the treatment. because of toxicity. The novel TKIs therapies constitute an important therapeutic challenge in this particularly subset of patients when compared with younger patients