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

12 th Congress of the European Hematology Association
and prednisone (CHOP) alone, or Rituximab + CHOP (EORTC 20981
study). Aims. To determine, from a Spanish perspective, if the maintenance
treatment with Rituximab is cost-effective alternative compared to the
current clinical practice of OA for the described population. Methods. Incremental
cost-effectiveness of Rituximab maintenance therapy (375 mg/m 2
every 3 months until progression or for 2 years) versus OA was assessed
through a deterministic, three health states (progression-free, progression
and death) transition model. Base case assumptions for the model included:
clinical evidence based on EORTC 20981 trial (extrapolation of PFS and
OS data using a Weibull distribution), Rituximab maintenance benefit to
last 5 years, 10 years time horizon, 3,5% discount rate on costs and benefits,
and Spanish National Health Service perspective (direct costs only).
Resource use (study drug, adverse events, treatments at relapse, surveillance/monitoring)
was estimated from a Spanish expert panel and EORTC
20981 trial. Unit costs were obtained from local databases (€ May 2,006).
Health states utility values were derived from an ad hoc study. Sensitivity
analyses were performed for all mentioned variables. Results. For the
base case (Table 1), more quality-adjusted life years (QALY), life-years (LY)
and progression-free survival years per patient on maintenance therapy
were obtained versus OA (incremental values of 0.85, 0.94 and 1.46,
respectively). Total cost per patient was higher with Rituximab than with
OA (+8,026 €). Incremental cost per QALY gained was 9,358 €, with a cost
per LY gained of 8,493 € and a cost per PFS year gained of 5,485 €. Sensitivity
analyses demonstrate results remains cost-effective for all variable
tested. Conclusions. Rituximab maintenance therapy, when compared to
observation alone, improves overall survival and progression free survival,
and is a cost effective strategy in patients with relapsed or refractory follicular
lymphoma who attain a response with further therapy.
Table 1. Results for base case (€ May 2, 2006)
Input Rituximab Observation Difference
Cost per patient(€) 22,458.20 14,432.40 8,026.06
Quality adjusted life years (QALY) 4,1133 3.2557 0.8576
Cost per QALY(€) 9,358.49 - -
Lyfe Years (LY) 5.6891 4.7441 0.9450
Cost per LY gained (€) 8,493.18 - -
Progression free survival (PFS) years 3.1952 1.7320 1.4632
Cost per PFS year gained (€) 5,485.39 - -
0304
ACTIVITY OF SINGLE-AGENT FLUDARABINE IN GASTRIC MALT LYMPHOMA: IMPACT OF
T(11;18)(Q21;Q21) IN MOLECULAR RESPONSE RATE
A. Salar, 1 B. Bellosillo, 2 A. Seoane, 3 A. Ferrer, 2 C. Pedro, 4
A. Alvarez-Larrán, 4 S. Serrano, 2 C. Besses4 1 2 Hospital del Mar, BARCELONA; Pathology Department, BARCELONA;
3 4 Endoscopy Department, BARCELONA; Clinical Hematology Department,
BARCELONA, Spain
Background. Fludarabine (F) is an active agent for the treatment of indolent
lymphoma. However, its clinical activity in the treatment of gastric
MALT lymphoma has not been studied in depth. Moreover, there is
scarce information regarding molecular response (MR) in gastric MALT
lymphoma treated by purine analogs and the prognostic value of t(11;18)
in this setting. Aims. The current study was undertaken to determine the
activity of single-agent fludarabine in gastric MALT lymphoma and to
analyze if these patients achieve molecular remission after this treatment.
Methods. Treatment consisted of fludarabine (25 mg/m 2 IV) given
on days 1-5, every 4 weeks, for 6 cycles; after the first cycle, oral fludarabine
was allowed to be given orally at 40 mg/m 2 with the same schedule.
Molecular response (MR) was assessed by RT-PCR analysis of
t(11;18) or by PCR assays for analysis of IgH gene rearrangements analyzing
FR1, FR2 and FR3 in endoscopic biopsies. Results. Eight consecutive
patients were entered on this trial. All but one patient were chemonaïve.
Median follow-up was 26 months (range 12-46 mo); median age
was 60 years (range: 45-77). Three pts were in stage I, 2 stage II-1 and 3
stage IV according to Lugano system. Four out of 5 (80%) pts achieved
a CR after three cycles and all eight cases achieved a CR after six cycles,
for an overall response rate of 100%. No patient has shown clinical or
endoscopic relapse at last follow-up. Hematological toxicity occurred in
75% of pts, mainly mild neutropenia and generally after the third cycle.
Three cases received G-CSF (after the 2nd, 3rd and 6th cycle) and three
patients required dose modification or delay (3-7 days) in the delivery
of the following cycle. No cases of autoimmune hemolytic anemia
developed. No blood transfusions were required. Only one patient had
to be admitted because of non-neutropenic fever that resolved with
110 | haematologica/the hematology journal | 2007; 92(s1)
broad-spectrum antibiotics. Four out of 8 pts (50%) achieved MR during
the study-period. Four out of 5 (80%) pts without t(11;18) achieved
MR (Figure 1). However, none case carrying t(11;18) achieved MR.
Sequencing of PCR products will be presented. Conclusions. Monotherapy
with intravenous or oral fludarabine is safe in gastric MALT lymphoma
and achieves a high response rate (100%). Only pts without
t(11;18) achieved MR and all those pts carrying t(11;18) had evidence of
clonal residual disease by PCR.
Figure 1.
0305
RITUXIMABS IMPACT ON LARGE B CELL LYMPHOMA TREATMENT
(ANALYSIS OF 116 PATIENTS OF A LYMPHOMA UNIT)
J. Alonso, 1 A. Canovas, 1 G. Barreiro2 1 2 Hospital Cruces.SVS.UPVVizcaya, BILBAO; Hospital de Cruces.UPV, BIL-
BAO, Spain
Background. A possible selection bias occurring in multicentric trials could
cause their outcomes not to be appliable to the real, nonselected population
of patients or to different environments. Aims. To validate the results
of chemotherapy added Rituximab in a population of non selected large B
cell lymphoma patients. Methods. We perform a comparative analysis of
response, time to first treatment failure and survival among all large B cell
lymphoma patients who received CHOP or alike chemotherapy in our
Lymphoma Unit since January 1997 until March 2002 (Historical
Cohort:HC) and the same outcomes in patients treated with Rituximab
added to similar schedules of chemotherapy since April 2002 until January
2007 (Rituximab Cohort: RC). Suspension due to intolerance, progression,
relapse or death was considered primary treatment failure. Complete remission
was defined by disappearance of disease or long term observation and/or
PET validated inactive residual mass. Different outcomes were defined as
non response. Demographic and prognostic variables, primary chemotherapy
response, time to primary treatment failure and overall survival were
analysed. Statistical Methods. Student’s T, chi*2, Kaplan-Meier’s survival
tables and log-rank test. Results. 116 patients were included: 57 in the first
period and 59 in the second one. No significant differences in the distribution
of sex (male/female ratio: 1,19 in HC and 0,69 in RC) or age (58 years
mean,15-84 years range in HC; 63 years mean, 17-88 years range in RC)
were observed between the two cohorts. The clinical stage (1-2 versus 3-
4: 23/34 in HC and 27/32 in RC) and IPI score were also similar (0-2/3-
5:26/31 in HC and 27/32 in RC). A non significant higher number of
patients with AIDS (5 versus 2) and mediastinal lymphoma (9 versus 1)
were detected in HC. A lower, non significant number of grade three follicular
lymphoma (2 versus 7), was found in HC. The extranodal lymphoma’s
rate was balanced (ten patients each). High dose chemotherapy
and stem-cell autotransplantation was administered as consolidaton therapy
in ten patients of HC and one of RC. A significantly higher proportion
of patients achieved complete remission in RC (93 versus 79%; p