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

0306
RISK-ADAPTED IMMUNOCHEMOTHERAPY OVERCOMES THE NEGATIVE PROGNOSTIC
IMPACT FCGRIIIA OF THE RECEPTOR GENOTYPE IN PATIENTS WITH FOLLICULAR
LYMPHOMA
V. Prochazka, S. Rozmanova, M. Jarosova, T. Papajik, K. Indrak
Teaching Hospital, OLOMOUC, Czech Republic
Background. Antibody (rituximab) dependent cellular cytotoxicity
(ADCC) is a key mechanism in killing CD20 + lymphoma cells. The Fc
portion of the rituximab molecule is bound by Fc receptors on the surface
of cytotoxic lymphocytes (NK cells). FCGR3A-158 V/F gene polymorphism
leads to expression of 3 variants of the FcγIIIa receptor (FcγRIIIa)
with different receptor affinity. The published studies with FL patients
treated with rituximab monotherapy demonstrated better outcomes of
patients with the V/V or F/V genotypes over the F/F genotype. Aims. To
assess whether the FcγIIIa receptor genotype influences the treatment
response quality (molecular remission) in newly diagnosed patients with
FL treated with risk-adapted immunochemotherapy. Methods. We studied
34 patients with newly diagnosed FL (grades I-IIIa) who had detectable bcl-
2/IgH (using standard or long-distance PCR) rearrangement in bone marrow
and/or peripheral blood. The median age was 55 years (31-84), 31 out
of 34 patients had advanced (III/IV) clinical stages. The FLIPI scores were
as follows: low 4/34, intermediate 13/34 and high 17/34. The first-line
treatment was stratified according to the generally used risk factors (FLIPI,
GELF, β-2-m level, bulk disease). Patients under 60 (65) years of age with
high-risk disease (FLIPI equal or more than 3, or additional risk factors)
were indicated to autologous stem cell transplantation (ASCT). Whereas
16 patients underwent ASCT, 18 patients were treated conventionally (R-
CHOP- or R-fludarabine-based regimens). The treatment response was
classified according to the standard Cheson criteria (1999). Patients who
achieved CR/CRu plus PCR bcl-2/IgH negativity were classified as CRm
(molecular CR). Genotyping of the FCGR3A-158 V/F gene was performed
using the PCR followed by allele-specific restriction enzyme digestion.
Results. Complete or unconfirmed complete response with Bcl-2/IgH negativity
(molecular remission) was achieved in 83.5% of patients, 1 patient
achieved CR, 4 patients had partial remission and one patient stable disease.
The frequencies of FcγRIIIa 158 V/V, V/F and F/F were 8.2%, 47.3%
and 44.7%, respectively. Homozygous FcγRIIIa 158 F/F carriers had higher
FLIPI index (chi square p=0.05), compared to V/F+V/V carriers. The
treatment modalities (conventional versus ASCT) had the same distribution
in V/V+V/F vs F/F patients (chi square p=0.38). The distribution of
CRm rate was not significantly different in the subgroups of V/V+V/F vs
F/F patients (chi-square, p=0.92). Summary. We found no difference in the
quality of treatment response (molecular remission) after first-line
immunochemotherapy among the FcγRIIIa subgroups. Risk-adapted intensive
concomitant immunochemotherapy overcomes the negative prognostic
impact of the FcγRIIIa genotype. The following question is whether
patients with the F/F genotype will have the same benefit from rituximab
maintenance treatment.
Supported by the grant of the Ministry of Education, Youth and Sports of the
Czech Republic (MSM 6198959205).
0307
90Y-IBRITUMOMAB TREATMENT FOR RELAPSED AND/OR REFRACTORY B CELL TYPE
NON-HODGKIN`S LYMPHOMA. MULTIINSTITUTIONAL ARGENTINIAN STUDY
R. Cacchione, J. Dupont, J. Milone, J. Bordone, L. Riera, M. Ardaiz,
M. Castro-Rios, M. Iabstrebner, G. Pombo, A. Basso, G. Avila,
S. Rodríguez, N. Tartas, J. Plana, G. Garay, D. Riveros, A. Carrasco,
F. Bezares
CEMIC, BUENOS AIRES, Argentina
Abstract. The radionucleid conjugate with monoclonal antibodies
(antiCD20/90Y-ibritumomab tiuxetan) have been approved for the treatment
of relapsed, refractory and transformed (high grade) follicular lymphomas.
Between September 2005 and February 2007, 27 patients with
refractory/relapsed lymphoma were enrolled. Median age was 58 yrs old
(45-76). Fourteen were women and 13 were men. Twenty-two were follicular
and 5 were mantle cell lymphoma. Ten patients had bulky disease,
5 had bone marrow involvement and 16 had stage III-IV disease. Time
from diagnosis was 0-3 years in 5 pts, 3-6 in 8 pts and over 6 years in 13
pts.. Eight pts had received 1-2 previous treatments, and 18 pts had
received 3-5 previous treatments including 5 pts with autologous bone
marrow transplantation. All had previously received anti-CD20 monoclonal
antibody therapy. Two pts. received previous radiotherapy. 90Y-
Ibritumomab (Zevamab TM Schering Argentina) was administered at 0,3
or 0,4 mCi, based on initial platelet count. Seven days before, and the same
12 th Congress of the European Hematology Association
day of the inmunoconjugate administration, pts received rituximab 250
mg/m 2 . Fifteen pts responded, (11 CR, 4 PR) and 10/11 CRs continued in
remission between 3 and 15 months of follow-up. Eleven pts required filgrastim
administration for neutropenia, 8 pts required platelet transfusions,
6 pts had neutropenia plus fever, 4 pts required red blood cells transfusion,
and only 5 pts had to be admitted for complicated pancytopenia.
One patient died 40 days after treatment with hypoplastic bone marrow
complicated with septicemia. Five pts with previous bone marrow transplantation,
required filgrastim, transfusions and 2/3 had febrile neutropenia.
Our experience shows 41% CR. Even heavily treated pts, that had
previous bone marrow transplantation were able to receive the radioimmunoconjugate,
although they required extra support. Our experience
favours the use of 90Y-Ibritumomab tiuxetan in relapsed and refractory
lymphomas even if they had received previous autologous bone marrow
transplantation.
0308
RITUXIMAB COMBINED WITH DEXABEAM SALVAGE THERAPY FOLLOWED BY HIGH DOSE
THERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY B-NHL: FIRST RESULTS OF A
PHASE II MULTICENTRE STUDY
G. Hess, 1 F.T. Flohr, 2 S.K. Kirschey, 1 H.W. Wolf, 3 N.F. Frickhofen, 4
W.R. Roesler, 5 H.L. Link, 6 N. B. Basara, 7 N.P: Peter,8 N.S. Schmitz, 9
E.W. Weidmann, 10 A.G.B Banat, 11 A.S. Schulz, 1 K.K. Kolbe, 1
G.D. Derigs, 2 C.H. Huber1 1 Johannes Gutenberg-University, MAINZ; 2 Städtisches Klinikum, FRANK-
FURT HÖCHST; 3 Uniklinik Halle, HALLE; 4Dr. Horst-Schmidt-Kliniken,
WIESBADEN; 5 Uniklinik Erlangen, ERLANGEN; 6 Westpfalz Klinikum,
KAISERLAUTERN; 7 Städt. Kliniken, IDAR-OBERSTEIN; 8 Carl-Thieme-
Klinikum, COTTBUS; 9 Asklepios Klinik St. Georg, HAMBURG; 10 Krankenhaus
Nordwest, FRANKFURT; 11 Uniklinkik Gießen-Marburg, GIEßEN
Background/Aims. HDT is an established treatment for relapsed aggressive
B-NHL (aNHL) and its use in indolent lymphoma (iNHL) is supported
by several trials. In a phase I study we could demonstrate the safety/feasibility
of the combination of Rituximab with Dexa-BEAM followed
by HDT with R-BEAM or R-TBI/CY for treatment of relapsed
lymphoma. Here we present the results of a prospective multicentre
phase II study testing the efficacy of this treatment. Methods. After
informed consent, patients aged 18-65, ECOG 0-2 with relapsed/refractory
B-NHL after at least 3 cycles of anthracycline-containing chemotherapy
were eligible. Rituximab (R) pre-treatment, but no prior HDT was
allowed. Treatment consisted of 2 cycles of R-Dexa-BEAM (dexamethasone
8 mg *3, day 1-10; BCNU 60 mg/m 2 , day 2; etoposide 75 mg/m 2 ,
day 4-7; cytarabinoside 200 2 mg/m 2 , day 4-7; melphalan 20 mg/m 2 , day
3; Rituximab 375 mg/m 2 , day 1). Stem cell mobilization was performed
after the second cycle. HDT-regimens were BEAM (BCNU: 300 mg/m 2 ,
day -7, etoposide 100 mg/m 2 day -6 - -3, cytarabinoside 400mg/m 2 in two
doses, day -6 - -3; melphalan 140 mg/m 2 day -2) or TBI/CY (total body
irradiation 12Gy, day -6 - -4; cyclophosphamide 60 mg/kgbw, day -3 - -
2;) in combination with 2 doses of Rituximab 375 mg/m 2 , day -7/-2.
Results. After ethics approval the study started 2001 and finished 2005.
Overall, 103/107 patients are evaluable for analysis. For 67 patients with
aNHL (DLCL 55, MCL 7, FL °3: 5) median age was 54 years (21-65) and
median number of pre-treatments was 1(1-2). A low/low intermediate
IPI was present in 74% and ECOG was 0 or 1 in 90% of aNHL patients.
The corresponding figures for 36 iNHL patients (FL °1-2: 29, MZL 6, IC
1) are: median age 55 (22-64), pre-treatments 1 (1-3), low/low intermediate
IPI and ECOG < 2 in 86 and 94%. Premature discontinuation: 28
patients did not proceed to HDT: treatment related mortality (sepsis,
cerebral hemorrhage) (3, aNHL), progression (12, aNHL), mobilization
failure (10, 8 aNHL, 2 iNHL), refusal (2, iNHL) or secondary cancer (1,
iNHL). Therefore, 66% of patients with aNHL and 86% with iNHL
underwent HDT. HDT (R-BEAM in 84% of aggressive and 75% of indolent
NHL) could be performed with manageable toxicity, 1 patient died
due to MOF. Recovery occurred timely (ANC > 500 median 11 days (8-
27). Restaging at day 60 revealed an ORR of 80% (59% CR, 21% PR) in
patients with aNHL and 90% (81, 10%) with iNHL. With a median follow
up of 2.2 years post HDT, PFS and OS for patients with aNHL are
63 and 83%. Corresponding figures for iNHL are: 63 and 100%. There
were no statistical differences between patients with or without R-pretherapy.
Conclusions. The inclusion of Rituximab in salvage therapy and
HDT resulted in high response rates and sustained remissions. R-containing
pre-therapy was not associated with inferior outcome, underlining
the continuous importance of HDT for relapsed/refractory lymphoma,
which seems to be further improved with the inclusion of R. With no
comparative studies available R-DexaBEAM followed by HDT can be
considered as an established relapse therapy for NHL.
haematologica/the hematology journal | 2007; 92(s1) | 111