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

12 th Congress of the European Hematology Association
0402
ORAL MELPHALAN, PREDNISONE AND LENALIDOMIDE FOR ELDERLY NEWLY
DIAGNOSED MYELOMA PATIENTS
A. Palumbo, 1 P. Falco, 1 P. Corradini, 2 C. Crippa, 3 F. Di Raimondo, 4
A. Falcone, 5 N. Nicola, 6 L. Canepa, 7 A. Gozzetti, 8 F. Morabito, 9
R. Knight, 10 J.B. Zeldis, 10 M. Boccadoro, 1 M.T. Petrucci 11
1 Az. Osp. S. Giovanni Battista, TORINO, Italy; 2 Istituto Nazionale Tumori,
MILANO, Italy; 3 Università di Brescia, Spedali Civili, BRESCIA, Italy;
4 Ospedale Ferrarotto, CATANIA, Italy; 5 IRCCS Casa Sollievo della Sofferenza,
SAN GIOVANNI ROTONDO (FG), Italy; 6 Università degli Studi di Parma,
PARMA, Italy; 7 Ospedale S. Martino, Univ. di Genova, GENOVA, Italy;
8 Az. Osp. Senese, Ospedale A. Sclavo, SIENA, Italy; 9 Az. Osp. di Cosenza,
COSENZA, Italy; 10 Celgene, SUMMIT (NJ), USA; 11 Università La Sapienza,
ROMA, Italy
Background. Lenalidomide plus dexamethasone is an effective treatment
in advanced and newly diagnosed multiple myeloma (MM). In
newly diagnosed patients the addition of thalidomide to the standard
oral melphalan and prednisone (MP) significantly increase response rate
and event free-survival (EFS) compared with MP. No data are available
on the potential additive and synergistic effect of the combination of MP
plus lenalidomide. Aims. This trial was a phase 1/2 multicenter, doseescalating,
open-label study designed to evaluate the dosing, safety and
efficacy of the association of MP plus lenalidomide (MPR) in newly diagnosed
symptomatic elderly MM patients. Primary end points were definition
of the maximum tolerated dose (MTD) and response rate; secondary
objectives were EFS and overall survival (OS). Methods. Fiftyfour
patients (median age 71 years, range 57-77) were enrolled in the
study and received 9 cycles of lenalidomide (5-10 mg/day for 21 days)
plus melphalan (0.18-0.25 mg/kg for 4 days) and prednisone (2 mg/kg
for 4 days) every 4-6 weeks, followed by maintenance therapy with
lenalidomide alone (10 mg/day for 21 days every month). Four different
dose-levels were tested. All patients received aspirin (100 mg/day),
as antithrombotic prophylaxis. Results. The MTD was lenalidomide 10
mg/day for 21 days and melphalan 0.18 mg/kg for 4 days every 4-6
weeks. At this dose-level partial response (PR) was observed in 81% of
patients, including 47.6% with at least a very good partial remission
(VGPR) and 23.8% who showed immunofixation negative complete
response (CR). The 1-year EFS and OS rates were 92% and 100%,
respectively. The presence of deletion of chromosome 13 or chromosomal
translocation (4;14) did not affect response rate and survival, while
high values of β2-microglobulin predicted a shorter EFS. Seventy percent
of patients received maintenance treatment with Lenalidomide alone
(median follow-up on maintenance 3,8 months). Major grade 3'4 adverse
events consisted of hematological toxicities (69.8%); major grade 3'4
non-hematological toxicities included febrile neutropenia (9.4%), cutaneous
rash (7.5%), and thromboembolism (5.7%); two of three thromboembolic
events occurred after aspirin discontinuation. Conclusions.
Oral MPR is a promising first-line treatment for elderly patients with
multiple myeloma. Hematological adverse were manageable and nonhematological
adverse events showed a low incidence. Aspirin appears
to be an effective antithrombotic prophylaxis. Un update of these data
will be presented at the meeting.
0403
TANDEM AUTOGRAFTING-NONMYELOABLATIVE ALLOGRAFTING FOR NEWLY DIAGNOSED
MULTIPLE MYELOMA: THE GITMO EXPERIENCE
L. Giaccone, 1 F. Patriarca, 2 M. Rotta, 1 N. Mordini, 3 D.G. Maloney, 4
M. Casini, 5 A. Rambaldi, 6 F. Carnevale-Schianca, 7 B. Allione, 8
D. Soligo, 9 P. Bavaro, 10 A.P. Iori, 11 R. Sorasio, 1 F. Fiore, 1 V. Montefusco, 12
A. Busca, 1 A. Parma, 13 L. Castagna, 14 E. Benedetti, 15 R. Fanin, 2
A. Gallamini, 3 P. Corradini, 12 A. Levis, 8 M. Aglietta, 7 E. Pogliani, 1
M. Falda, 1 M. Massaia, 1 A. Palumbo, 1 B. Sandmaier, 16 R. Storb, 16
M. Boccadoro, 1B. Bruno17 1 Azienda Ospedaliera San Giovanni Battist, TORINO, Italy; 2 University of
Udine, UDINE, Italy; 3 Azienda Ospedaliera Santa Croce e Carle, CUNEO,
Italy; 4 Fred Huthcinson Cancer Research Center, SEATTLE, USA; 5 Azienda
Ospedaliera San Maurizio, BOLZANO, Italy; 6 Ospedali Riuniti, BERGAMO,
Italy; 7 IRCC, CANDIOLO, Italy; 8 Azienda Ospedaliera SS Antonio e Biagio,
ALESSANDRIA, Italy; 9 IRCCS, Ospedale maggiore, MILANO, Italy;
10 Ospedale civile, PESCARA, Italy; 11 Università La Sapienza, ROMA, Italy;
12 Istituto Nazionale Tumori, MILANO, Italy; 13 Ospedale san Gerardo, MON-
ZA, Italy; 14 Istituto Clinico Humanitas, ROZZANO, MI, Italy; 15 Università di
148 | haematologica/the hematology journal | 2007; 92(s1)
Pisa, PISA, Italy; 16 Fred Hutchinson Cancer Research Center, SEATTLE, USA;
17 Azienda Ospedaliera San Giovanni Battist, TORINO, Italy
Background. Allografting induces long-term molecular remissions and
possibly cure in myeloma patients. The development of nonmyeloablative
conditionings has reduced the transplant-related mortality (TRM)
and extended the eligible age for transplantation up to 65-70 years. However,
prior cytoreductive high-dose chemotherapy appears to play a key
role in the achievement of high response rates. Aims. We report the
results of a GITMO (Gruppo italiano trapianto midollo osseo) multicenter
trial which evaluated efficacy and safety of a hematopoietic stemcell
autograft followed by a nonmyeloablative allograft from an HLAidentical
sibling in patients with newly diagnosed myeloma. Methods.
One hundred and six patients from 15 Italian centers were enrolled.
Four patients did not complete the program because of consent withdrawal
and were then excluded from the analysis. The median age was
54 years (range 30-65), 70 patients out of 102 had stage III myeloma and
β2microglobulin was greater than 3,5 mg/dL in 33. All patients were
initially treated with vincristine, doxorubicin, and dexamethasone, after
which peripheral-blood stem cells (PBSC) mobilized by cyclophosphamide
and granulocyte colony-stimulating factor (G-CSF) were collected.
Upon recovery, patients were treated with 200 mg/m 2 melphalan
followed by autologous stem-cell rescue. About 2 months later, they
received 2 Gy total-body irradiation and infusion of G-CSF mobilized
PBSC from an HLA-identical sibling. Graft-vs-host disease (GVHD) prophylaxis
included cyclosporin and mycophenolate mofetil. Results. After
autologous transplantation overall response rate was 77% (79/102), with
7/102 complete remission (CR). Following allografting, all patients
promptly achieved donor engraftment. The overall response rate was
91% (93/102), with 56 patients achieving CR. Among patients progressed
after allografting, 16 were treated with donor lymphocyte infusion,
8 of them received prior cytoreductive therapy, and 4/16 obtained
a transient disease response. Incidence of grade 2-4 acute GVHD was
40% (41/102), including 4 patients with grade 4. Overall, chronic GVHD
was observed in 74% (73/99) of patients alive at least 3 months after allografting,
GVHD was graded as extensive in 50 of them. After a median
follow-up of 48 months (range, 14-103) from diagnosis, median overall
survival was not reached with follow-up extending to 7 years. Causes
of deaths were TRM in 14 patients, disease progression in 6 and second
tumor in 3. Median event-free-survival (EFS) was 38 months (range 10-
103). Summary and conclusions. This reports shows that the combination
of autologous transplant followed by allografting from an HLA-identical
sibling is feasible in patients with newly diagnosis myeloma up to
65 years of age and demonstrates efficacy in terms of disease control and
reduced toxicity by separating the cytoreductive effect of high dose
chemotherapy from the graft-versus-myeloma effect of allografting.
0404
BORTEZOMIB PLUS MELPHALAN AND PREDNISONE (VMP) IN ELDERLY UNTREATED
PATIENTS WITH MULTIPLE MYELOMA: PROGNOSTIC FACTORS INFLUENCING TIME TO
PROGRESSION
M.-V.M. Mateos, 1 J.-M. Hernández, 2 M.-T. Hernández, 2
N.-C. Gutiérrez, 2 L. Palomera, 2 M. Fuertes, 2 P. García, 2 J.J. Lahuerta, 2
J. De la Rubia, 2 M.J. Terol, 2 A. Sureda, 2 J. Bargay, 2 P. Ribas, 2
F. De Arriba, 2 A. Alegre, 2 A. Oriol, 2 D. Carrera, 2 J. García-Laraña, 2
R. García-Sanz, 2 J. Bladé, 2 F. Prosper, 2 D.-L. Esseltine, 3 H. Van de Velde, 4
J.-F. San-Miguel2 1 2 University Hospital of Salamanca, SALAMANCA, Spain; Hematology Division,
Grupo Español de MM, SPAIN, Spain; 3Millennium Pharmaceuticals,
Inc., CAMBRIDGE, MA, USA; 4Johnson & Johnson Pharmaceutical Researc,
BEERSE, Belgium
Between January 2004 and April 2005, the Spanish PETHEMA group
conducted a phase I/II trial in which 60 newly diagnosed MM patients
older than 65 years were included and received four 6-weeks cycles of
bortezomib 1.0 or 1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29 and 32 followed
by a 10-day rest period, in combination with oral melphalan 9
mg/m2 and oral prednisone 60 mg/m2 , both on days 1 to 4. This was followed
by five cycles of weekly bortezomib in combination with melphalan
and prednsone. No Dose Limiting Toxicity occurred during the
phase I; therefore, the 1.3 mg/m2 dose was expanded to the phase 2.
With a median follow-up of 26 months (range: 15-38) we confirm the
response rate of 88% previously reported including 32% of IF-negative
CRs, 11% IF-positive CRs and 45% of PR. The median time to progression
(TTP) time was 27,2 months (95% CI: 22-32) and the median overall
survival (OS) time has not been reached and the estimated 3-year OS