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

Response was defined according to EBMT criteria. Patients with PD
were removed from the study, the others continued until best response
for a maximum of 6 cycles. LVEF was evaluated before and at the end
of treatment. Time to response was from the date of study entry to the
first evidence of response, time to progression (TTP) from the date of first
response to progression. Results. as of February 28 th 2007, 65 patients
were enrolled, 28 received LD-VTD (group1) and 36 LD-VTD+My
(group2). 13(20%) pts did not receive thalidomide due to previous neurotoxicity.
Patients characteristics and results are reported in Table 1. As
expected, haematologic toxicity was more frequently recorded in group2
and resulted in a major incidence of infections. Extra-haematologic toxicity
was negligible in both groups and no patient experienced progression
of PN. No case of DVT or cardiac failure was recorded and most
patients were treated on an outpatient basis. Median time to response
was 2 and 1,2 months, ORR 50% and 73% (p=0,04), median TTP 7 and
16 months (p=0,02) in group1 and 2, respectively. OS of the two groups
was comparable. At the day of last follow-up, 11 group1 and 27 group2
patients were alive. Conclusions. liposomal doxorubicin increases the
antimyeloma efficacy of bortezomib, thalidomide and dexametasone
combination regimen with acceptable toxicity in elderly and heavily
pre-treated patients. This might translate in a prolonged OS but an
extended follow-up is needed.
0260
FEASIBILITY AND EFFICACY OF BORTEZOMIB RE-TREATMENT IN MULTIPLE MYELOMA
S. Ciolli, F. Leoni, C. Casini, A. Bosi
Azienda Universitaria Ospedaliera Caregg, FLORENCE, Italy
Background. despite improved response and survival, multiple myeloma
(MM) still relapse and remain an incurable disease. Safety and efficacy
of bortezomib in previously treated MM, either as single agent or
with thalidomide or standard chemotherapeutics, have been well established.
However, no therapy is curative and upon relapse myeloma cells
develop resistance to therapies that had been previously effective. Until
recently, few data are available on the feasibility and benefits of re-treatment
with bortezomib which is a weak substrate for multi-drug resistance
efflux pumps and has the potential to avoid resistance. To assess
the safety and efficacy of bortezomib re-treatment in advanced MM, we
reviewed the outcome of patients who were re-challenged with bortezomib
after a previous response in our institution. Methods. since January
2005, all myeloma patients previously treated with a bortezomib
based therapy and achieving at least a stable disease were considered
suitable for re-treatment. They were required a measurable disease and
a life expectancy >1 months. Planned therapy was: bortezomib (Velcade
® ) 1.0 mg/m2 i.v. bolus days 1, 4, 8 and 11 of a 28-d cycle, oral dexamethasone
24 mg on the day of and the day following each Velcade
dose. Patients receiving thalidomide (50/100 mg) as maintenance continued
the drug, if not contraindicated. Adverse events were assessed at
each visit and graded according to NCI criteria. Efficacy was assessed
after each cycle and response defined according to EBMT criteria.
Patients with PD were removed from the study, the others continued
until best response for a maximum of 8 cycles. Overall survival (OS)
was from the date of bortezomib re-treatment to the date of death or last
follow-up. Time to progression (TTP) from the date of first response to
progression. Results. as of February 28th 2007, 11 were the patients retreated.
They all had a progressive disease, were heavily pre-treated and
in most of them neuropathy of any grade was present. Patients characteristics:
median age 64 yrs (42-80), 8 stage III (2 stage IIIB), 5
β2microglobulin >4 mg/L, WBC 3.7×109 /L ((2.0-9.7), haemoglobin 10
gr/dL(7,8-14,5), platelets 135×109 /L(10-258). Median time from diagnosis
to first bortezomib was 4 yrs (1-15,8) and a median of 4 (1-8) were
the previously delivered therapy lines. 4 were the patients relapsed after
a bone marrow transplant prior to first bortezomib. Toxicity was negligible,
not increased in comparison with first bortezomib therapy. Grade
1 neutropenia was recorded in two patients, grade 2 thrombocytopenia
in 2. A negative impact on haemoglobin level was never registered. Overall,
the most commonly reported adverse events of grade >1 were fatigue
(50%) and nausea (22%). There was not a clinical progression of preexisting
neuropathy. At the date of last follow-up, 10 patients were valuable
for response. 6 patients, who had achieved a response with first
bortezomib, again responded (4 nCR , 2 PR) while 4 SD with the previous
bortezomib, again achieved a SD. After a medium follow-up of 13
months, 5 patients were alive. Median TTP was 9 (2-12) months. Conclusions.
bortezomib re-treatment is safe, effective and not associated
with new or cumulative toxicity. Responsive patients may benefit from
re-challenging the drug.
12 th Congress of the European Hematology Association
0261
SALVAGE THERAPY WITH INTRAVENOUS BORTEZOMIB, MELPHALAN AND
DEXAMETHASONE IN PREVIOUSLY TREATED MYELOMA PATIENTS
F. Di Raimondo, 1 A. Chiarenza, 1 V. Del Fabro, 1 L. Schinocca, 1
P. Fiumara, 1 G.A. Palumbo, 1 C. Conticello, 2 G. Amato, 2 R. Giustolisi1 1 Hematology Dept, Univ.of Catania, CATANIA; 2 Mediterranean Institute of
Oncology, VIAGRANDE, CATANIA, Italy
Background. Bortezomib, Melphalan, and Steroids are among the most
effective drugs for treatment of multiple myeloma and their combination
has already tested in elderly myeloma patients. However, so far the
contemporary administration of these drugs has not been explored. Aims.
We therefore designed a protocol with monthly courses of contemporary
intravenous administration of these drugs in patients with advanced
multiple myeloma. Methods. Bortezomib was given at dosage of 1.3
mg/m 2 i.v. days 1,4,8,11, Melphalan 5 mg/m 2 i.v. days 1,4,8,11, Dexametasone
40 mg days 1-2, 4-5, 8-9, 11-12. So far, 21 patients have been
enrolled. Median age was 64.5 (range 53-82). All patients had been
already treated with a median of 2 previous lines of treatment (range 1-
6) including autologous bone marrow transplant in 7 patients and and
Bortezomib alone or in combination in 5 patients. All patients included
in this study were no longer eligible for a bone marrow transplant procedure.
Fourteen patients were resistant to previous therapies while 7
were considered as relapsed. Results. Hematological toxicity grade 3 and
4 occurred in 38%, 36%, 33%, and 50% after I, II, III, and IV cycle
respectively of patients after the first cycle. Three patients developed also
grade 3 non-hematological toxicity (Herpes zoster, vomit). So far, 4
patients have stopped treatment for toxicity after 1, 3, 3, and 4 courses.
All of these patients were in stable disease. Five patients achieved a very
good partial remission (M-protein not detectable at electrophoresis), 5
patients a partial remission (reduction of M-protein > 50%) while in two
other patients reduction of the M-protein was associated with increase
of bone marrow plasmacells. Two patients were in stable disease, one
was in progression and 2 are not yet evaluated. Conclusions. The contemporary
intravenous administration of Bortezomib, Melphalan, and Dexametasone,
appears to be an highly effective treatment even for heavily
pretreated patients. However, in these patients, haematological toxicity
was the limiting factor. Therefore, the dosage of the drugs or their
schedule has to be modified.
0262
SALVAGE TREATMENT WITH MELPHALAN 100 MG/M2 IN FULMINANT PROGRESSION OF
MULTIPLE MYELOMA
R. Hajek, 1 M. Krejci, 2 A. Krivanova, 2 L. Pour, 2 Z. Adam, 2 L. Zahradova, 2
E. Vetesnikova, 2 J. Mayer, 2 J. Vorlicek2 1 2 Czech Myeloma Group, BRNO; IHOK University Hospital and IHOK LF
MU, BRNO, Czech Republic
Background. Patients with a rapid fulminant progression of multiple
myeloma (PGMM) have poor prognosis. The treatment options are very
limited due to a pancytopenia and/or a general poor status of patients.
The treatment with melphalan (MEL) 100 mg/m 2 as a salvage therapy up
front followed by infusion of stored autologous peripheral blood stem
cells (PBSCs) can stop PGMM almost immediately. This strategy provides
a window of opportunity for the application of new immunomodulatory
or targeted drugs, such as thalidomide and bortezomib as consolidation
treatment. Aims. The aim of our analysis was to evaluate the
efficacy and toxicity of MEL 100 mg/m 2 (MEL 100) with PBSC support
in the PGMM after the first autologous transplantation. Methods. We
have retrospectively evaluated 18 patients with fulminant PGMM treated
with MEL 100 in our centre from 2004 to 2006. Median follow-up
from MEL 100 was 5 months (range: 3-14 months). The baseline characteristics
of the patients are as follows: median age 58 years (range: 40-
68); median number of relapse 1 (range: 1-4); clinical stages according to
Durie and Salmon 17%-II/83%-III; clinical stages according to ISS 1-
28%/2-44%/3-28%; extramedullary disease in 40% (7/18), renal impairment
in 22% (4/18), high degree of bone marrow infiltration with
peripheral pancytopenia in 61% (11/18). Following the MEL 100 salvage
regimen, the patients were treated mostly with bortezomib (5/18) or
with thalidomid based regimen (10/18). Results. There was no treatmentrelated
mortality. The median time to the neutrophils engraftment
(above 0.5×10 9 /L) was 11 days (range: 7-12 days); the median duration
of hospitalization after MEL 100 was 21 days (range: 13-90). Mucositis
grade 3-4 developed in 27% (5/18) of patients, and febrile neutropenia
occurred in 44% (8/18) of patients. Overall response rate (ORR) was
61% (11/18) and only 1 patient had continuous progression. Very rapid
haematologica/the hematology journal | 2007; 92(s1) | 95