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

0862
COMPARISON OF DASATINIB TO HIGH-DOSE IMATINIB IN PATIENTS W320HO
EXPERIENCE IMATINIB FAILURE: RESULTS FROM A RANDOMIZED, PHASE-II TRIAL
(CA180017, START-R)
G. Martinelli, 1 P. Rousselot, 2 T. Robak, 3 T. Masszi, 4 A. Skotnicki, 5
A. Hellmann, 6 T. Hughes, 7 A. Countouriotis, 8 D. Dejardin, 8 B. Druker 9
1 Universita Di Bologna, BOLOGNA, Italy; 2 Hôpital Saint-Louis, PARIS, France;
3 Medical University of Lodz, LODZ, Poland; 4 National medical Center,
BUDAPEST, Hungary; 5 Jagiellonian University, KRAKOW, Poland; 6 Gdansk
Medical School, GDANSK, Poland; 7 Inst. of Medical & Veterinary Science,
ADELAIDE, Australia; 8 Bristol-Myers Squibb Co., WALLINGFORD, USA;
9 Oregon Health & Science University, OREGON, USA
Background. Relapses on imatinib at doses of 400-600 mg/d are a wellrecognized
problem occurring in approximately 13% of newly-diagnosed
chronic-phase (CP) CML patients with 5 years of follow-up. Effective
therapeutic options for these patients are limited. Escalating imatinib doses
to 800 mg/d may overcome resistance in some cases and dasatinib, a
novel BCR-ABL kinase inhibitor, has also been shown to be safe and
effective in this population. Unlike imatinib (and its analog nilotinib),
dasatinib binds to the active, oncogenic conformation of BCR-ABL. Aims.
To assess the relative efficacy and safety of dasatinib and high-dose imatinib
in patients with imatinib-resistant CP-CML. Methods. Patients with
CP-CML with primary or acquired resistance to conventional doses of
imatinib (400-600 mg/d) were randomized on a 2:1 basis to dasatinib 140
mg (70 mg bid) (N=101) or imatinib 800 mg (400 mg bid) (N=49) as part
of this international, multicenter study. Primary resistance was defined as
a lack of complete hematologic response (CHR) at 3 months, lack of any
cytogenetic response (CyR) at 6 months, or lack of major CyR (MCyR)
at 12 months. Relapse after a HR or MCyR was considered as acquired
resistance. Crossover to the alternate regimen was permitted following
confirmed progression, lack of MCyR at Week 12, or intolerance (Grade
3-4 non-hematologic toxicity or hematologic toxicity requiring multiple
dose modifications). Dose escalation of dasatinib to 90 mg bid or reduction
to 50 mg bid or 40 mg bid were allowed for inadequate response or
adverse events, respectively. A 600-mg dose of imatinib was permitted
for toxicity for patients who had not previously received imatinib 600 mg.
Results. Patient characteristics were well balanced at baseline (median age
51 years; median time form diagnosis 59 months), with one exception;
BCR-ABL mutations were 2-fold more frequent for the dasatinib treatment
group (45% vs. 22%). With follow-up now extending to 21 months,
results are consistently in favor of dasatinib over high-dose imatinib in
terms of: CHR (93% vs. 82%; p=0.034), MCyR (52% vs. 33%; p=0.023),
complete CyR (CCyR) (40% vs. 16%; p=0.004), major molecular response
(16% vs. 4%; p=0.038), time to treatment failure (hazard ratio [HR], 0.16;
p1 adverse factors according to stage-modified IPI (MIPI) were more frequent.
The commonest treatment was a short course of anthracyclinebased
chemotherapy (CHT) + involved field radiotherapy (IFRT). Fortytwo
percent of T patients also underwent surgery. Only 28/428 (6.5%)
received CNS prophylaxis. The CR rate ranged from 79% (CS) to 95%
(OC), while relapse was most common in SG (31%) and prevailed in distant
sites (60%). Four patients (1 WR, 1 SG, 2 NPS), without CNS prophylaxis,
relapsed in CNS (0.8%) and 4 WR patients (0.8%) in GI tract.
After a median follow-up of 49 months (range 1-219 months), 5-yr OS,
EFS and DFS were 72%, 59% and 74%, respectively. OS varied among
different locations from 51% (T) to 89% (OC). It is noteworthy that CS
patients did not fare worse than those with disease presenting in single
sites. In all presentations with the exclusion of T patients, 5-yr EFS differed
according to MIPI (MIPI 0-1, 68% vs. MIPI >1, 49%; p=0.0001) and
CHT+IFRT (combined treatment) (CHT 43% vs. CHT+IFRT 71%;
p=0.0001) as confirmed by Cox multivariate analysis (MIPI, p=0.012;
combined treatment, p=0.0001). However, in thyroid involvement MIPI
seems to be not predictive of survival due to a high mortality unrelated
to disease. Moreover, T patients seem to benefit more from surgery in
combination with chemotherapy and/or IFRT than from other treatments
not including partial or complete thyroid resection (p=0.04). Conclusions.
patients with DLBCL of different head and neck sites represent a heterogeneous
group regarding clinical characteristics, prognostic factors and
outcome. A low MIPI and a combined treatment with addition of radiotherapy
influence the outcome favorably. Moreover, a very low rate of
CNS recurrence suggests that CNS prophylaxis may not be mandatory
for these patients.
0864
THE CHARACTERISTICS AND CLINICAL COURSE OF MALT-LYMPHOMA:
THE UNIVERSITY OF VIENNA EXPERIENCE
M. Raderer, M. Troch, S. Woehrer, B. Streubel, A. Puespoek,
K. Turetschek, M. Formanek, U. Jaeger, W. Hauff, J. Drach, A. Chott
University of Vienna, VIENNA, Austria
Background. A prospective assessment of clinical characteristics and
potential risk factors affecting outcome in patients with MALT lymphoma
was performed at our institution. Patients and Methods. Between 1997-February
2007, a total of 173 consecutive patients with histologically verified
MALT lymphoma (101 female / 72 male) underwent uniform staging and
assessment of clinical characteristics including assessment of genetic
changes, presence of autoimmune disease (AD), Helicobacter pylori (HP)-
haematologica/the hematology journal | 2006; 91(s1) | 321