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

is 85%. Seven out of the 25 relapsed patients are considered to have a
biological but asymptomatic relapse and remains untreated with a median
follow-up from the biological progression of 2,5 months (range: 1-8).
We analyzed the influence of variables with known prognostic factors
in MM in TTP and we observed that hypoalbuminemia (0,05). Toxicity was
manageable and predictable; principal toxicities were haematologic, gastrointestinal,
and peripheral neuropathy and were more evident during
early cycles and in patients older than 75 years old. In conclusion, prognostic
factors such as hypoalbuminemia, poor Karnofsky performance
status and high S-phase were associated with a shorter TTP; by contrast,
VMP overcomes the adverse prognosis conferred by age and cytogenetics
abnormalities.
0405
POOR PROGNOSIS ASSOCIATED WITH GAIN OF CHROMOSOME 1Q21 IN MULTIPLE
MYELOMA MAY BE OVERCOME BY TREATMENT WITH A BORTEZOMIB COMBINATION
V. Sagaster, 1 V. Odelga, 1 H. Kaufmann, 1 J. Ackermann, 1 M. Galhuber1 N. Zojer, 2 H. Ludwig, 2 R. Wieser, 1 C. Zielinski, 2 J. Drach1 1 2 Medical University of Vienna, VIENNA; Wilhelminenspital, Dept. of Medicine
I, VIENNA, Austria
Background. Bortezomib is an active agent for treatment of multiple
myeloma (MM) and may even be effective in patients (pts) with adverse
prognostic factors including unfavorable cytogenetic abnormalities.
However, it is unknown whether or not bortezomib may overcome the
negative prognostic impact of a chromosome 1q21 (CKS1B) gain, which
has recently been reported as a negative prognostic factor even in the setting
of a total therapy approach. Aims. We therefore evaluated chromosome
1q21 among other abnormalities in 46 pts with relapsed/refractory
MM who were treated with single-agent bortezomib (1.3 mg/m 2 on
days 1, 4, 8, and 11 every 3 weeks) and in 28 pts treated with a bortezomib
combination (bortezomib/dexamethasone in 43%, bortezomib/
chemotherapy in 46%, bortezomib/ thalidomide/dexamethasone in
11%). Patients and Methods. Median age of pts was 63 years (range, 40 -
82 ) and median time to bortezomib therapy was 40 months (median
number of prior therapies: 3; 96% of pts had high-dose pulsed dexamethasone,
61% thalidomide, 85% alkylating agents, and 41% high-dose
melphalan). Chromosome 1q21 was evaluated by interphase FISH with
a CKS1B-specific probe. Results were correlated with clinical outcome.
Results. Among patients treated with single-agent bortezomib, gain of
1q21 was observed in 20 of the 46 pts (43.5%). Treatment outcome after
bortezomib was negatively affected by presence of a 1q21 gain: The
overall response rate was 30% (versus 58% in pts with normal 1q21;
p=0.06) and the CR/near-CR rate was 10% (versus 23%). Moreover,
gain of 1q21 was associated with shortened time to treatment failure
(TTF) (median, 2.4 versus 6.6 months; p=0.043) and overall survival (OS)
(median, 4.4 versus 19.8 months; P = .003) compared to pts with normal
1q21. β-2-microglobulin and 14q32 translocations were unrelated to
treatment outcome after single-agent bortezomib, but median OS was
short in the presence of low serum albumin (4.8 versus 17.8 months;
p=0.036). In the group of pts treated with a bortezomib-combination, 11
of the 28 pts had a 1q21 gain (39%). There were no significant differences
between pts with 1q21 gain and normal 1q21 regarding overall
response (54.5% versus 64.7%), CR/near-CR rate (27% versus 29%),
median TTF (8.2 versus 6.9 months; p =0.57) and median OS (not
reached versus 17.8 months; p=0.49). Conclusions. FISH-defined gain of
1q21 is associated with poor response, short TTF and short OS after single-agent
bortezomib; however, these differences disappeared in the
context of a bortezomib-combination therapy. These results provide further
evidence for the efficacy of bortezomib-combinations in MM
patients with high-risk features.
Non-Hodgkin's lymphoma - Clinical I
0406
PROSPECTIVE, MULTICENTER RANDOMIZED GITMO/IIL TRIAL COMPARING INTENSIVE
(R-HDS) VERSUS CONVENTIONAL CHEMOIMMUNOTHERAPY (CHOP-R) IN HIGH-RISK
FOLLICULAR LYMPHOMA AT DIAGNOSIS: THE SUPERIOR MOLECULAR REMISSION (MR)
RATE OF R-HDS EXPLAINS ITS BETTER CLINICAL PERFORMANCE
M. Ladetto, 1 F. De Marco, 1 F. Benedetti, 2 U. Vitolo, 3 C. Patti, 4
A. Rambaldi, 5 A. Pulsoni, 6 M. Musso, 7 A.M. Liberati, 8 A. Olivieri, 9
A. Gallamini, 10 E. Pogliani, 11 D. Rota Scalabrini, 12 V. Callea, 13
F. Di Raimondo, 14 V. Pavone, 15 A. Tucci, 16 S. Cortelazzo, 17 A. Levis, 18
M. Boccadoro, 1 I. Majolino, 19 A. Pileri, 1 A.M. Gianni, 20 R. Passera, 3
P. Corradini, 20 C. Tarella1 1 Università di Torino, TORINO; 2 Policlinico Borgo Roma, VERONA; 3 A.O San
Giovanni Battista, TORINO; 4 Ospedale V.Cervello, PALERMO; 5 Ospedali
Riuniti, BERGAMO; 6 Università La Sapienza, ROMA; 7 Ospedale La Maddalena,
ROMA; 8 Policlinico Monteluce, PERUGIA; 9 Ospedale Torrette,
ANCONA; 10 A.O Santa Croce, CUNEO; 11 A.O Gerardo de Tintori, MON-
ZA; 12 IRCC, CANDIOLO; 13 A.O Bianchi-Melacrino-Morelli, REGGIO CAL-
ABRIA; 14 A.O Ferrarotto, CATANIA; 15 Policlinico, BARI; 16 Ospedali Civili,
BRESCIA; 17 A.O S. Maurizio, BOLZANO/BOZEN; 18 A.O SS.Antonio e Biagio,
ALESSANDRIA; 19 Ospedale S. Camillo, ROMA; 20 Istituto Nazionale
Tumori, MILANO, Italy
Background. The superiority of intensified chemotherapy with autologous
stem cell transplantation (ASCT) as the first-line treatment in follicular
lymphoma (FL) is uncertain, particularly since the introduction of
rituximab. The GITMO-IIL trial evaluated if an intensified treatment with
ASCT is better than conventional chemotherapy (both supplemented
with Rituximab) in high-risk FL at diagnosis. Objectives. This is a multicenter
randomized open-label phase III trial. The analysis was intention
to treat with event-free survival (EFS) as the primary endpoint. Crossover
from CHOP-R to R-HDS was allowed. Centralized PCR-based molecular
analysis was performed. The whole patient (pt) population is now
evaluable for analysis with a median follow-up of 39 months. Methods.
Eligibility required a FL with aaIPI>1 or IIL>2 score and an age of 18-60.
Secondary endpoints were PFS, DFS, OS, rate and prognostic value of MR.
R-HDS and CHOP-R have been already described (Ladetto et al ASH
2005, Rambaldi et al Blood 2002). Planned sample size was 240 to detect
a 20% absolute increase in the 3-years EFS. However the trial was
stopped at 136 pts due to R-HDS EFS superiority at a planned interim
analysis. Cross-over was allowed after CHOP-R failure. Centralized PCRbased
molecular analysis was planned on BM cells.
Figure 1.
12 th Congress of the European Hematology Association
haematologica/the hematology journal | 2007; 92(s1) | 149