12th Congress of the European Hematology ... - Haematologica

Results. From July 2005 through March 2006, 662 patients (median age
55 years; 47% male) were randomized and received treatment. Median
time from CML diagnosis to randomization was 54 months. With a
median duration of treatment of 8 months, marked and similar hematologic
and cytogenetic response rates were seen across all four treatment
groups (Table 1). Duration of CyR and progression-free survival were
also similar across all treatment groups. Toxicities identified as being of
special interest were fewer for the 100-mg QD regimen (Table 1); pleural
effusions (p=0.024) and thrombocytopenia (p=0.004) were both
markedly reduced in the 100-mg QD group compared with the 70-mg
BID arm. There were fewer dose interruptions and reductions and the
lowest number of patients discontinuing treatment for drug-related toxicity
in the 100-mg QD treatment group. Summary and Conclusions. Dasatinib
100 mg QD offers the most favorable overall benefit-risk assessment
in this CP-CML patient population.
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DASATINIB IS SAFE AND EFFECTIVE IN PATIENTS WITH PREVIOUSLY UNTREATED
CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE
A. Quintas-Cardama, 1 H. Kantarjian, 1 S. OBrien, 1 D. Jones, 1
G. Borthakur, 1 C. Nicaise, 2 J. Cortes1 1 2 MD Anderson Cancer Center, HOUSTON; Bristol-Myers Squibb Co.,
WALLINGFORD, CT, USA
Background. Dasatinib is a multi-targeted kinase inhibitor of BCR-ABL
and SRC. Based on its high level of activity in patients with imatinibresistant
or -intolerant CML-CP, the present phase-II trial was designed
to assess the efficacy and safety of dasatinib in previously untreated
CML-CP patients. The primary objective was to estimate the proportion
of patients attaining major molecular response (BCR-ABL/ABL ratio
30%, ZAP-70 >20%,
unfavourable cytogenetics (trisomy 12 or del11q or del17p). Seventy-nine
CLL patients, median age 60 years (range 37-74) received six monthly
courses of Flu (25 mg/m 2 for 5 days) and four weekly doses of rituximab
(375 mg/m 2 ) starting after completion of Flu therapy. According to modified
Rai stages, 9 patients had a low stage, 67 an intermediate stage and
3 a high stage. Based on NCI criteria, 63/79 (80%) patients achieved a
complete remission (CR), 12/79 (15%) a partial remission (PR) and 4/79
(5%) a stable disease (SD) or no response or progression. Three patients
presented grade 3 (WHO) infective lung toxicity and 1 patient acute fatal
B hepatitis. Hematologic toxicity included mainly neutropenia (grade 3
and/or 4 in 41 pts) and thrombocytopenia (grade 3 and/or 4 in 4 pts).
Thirty-five patients in clinical CR or PR, either with CD5 + CD19 + CD79b _
(MRD) bone marrow (BM) cells >1% (n=20 pts) or with MRD peripheral
blood lymphocytes (PBL) >1000/mL (n=15 pts) within 1 year after completion
of the induction treatment, underwent consolidation/maintenance
therapy with four monthly cycles of rituximab at 375 mg/m 2 followed by
twelve monthly low doses of rituximab at 150 mg/m 2 . The median follow-up
duration was 38 months. Noteworthy, all B-CLL pts experienced
a long progression-free survival (PFS) from treatment (69% at 6 years).
Nevertheless, CLL patients that underwent consolidation therapy (n=35)
showed a significant longer duration of response in comparison with the
subset of not consolidated and BM or PBL MRD positive (n=13) patients
(85% vs 20% at 5 years, p=0.00001, Figure 1).
Figure 1. Duration of response in consolidated vs unconsolidated pts.
haematologica/the hematology journal | 2007; 92(s1) | 129