Haematologica 2003 - Supplements

PURPOSE: To evaluate the outcome of 35 consecutive patients
with a novel total myeloma multiple protocol and its relation with
classic prognosis features at diagnosis.
PATIENTS AND METHODS: Between January 2000 and
December 2002 we studied 35 consecutive patients with multiple
myeloma. Patients younger 60 years old were treated with i.v.
chemotherapy (regimens containing cis-platin, etoposide,
anthracyclines, vincristine and corticosteroids). Chemotherapy
responders and refractory patients with response to oral
thalidomide plus dexamethasone and/or rituximab were
underwent to autologous transplantation followed of oral
thalidomide. Patients with resistance were treated with a dosescalating
schedule of thalidomide. Patients between 60 and 65
years old were aleatorized into i.v. chemotherapy followed of
thalidomide or melphalan-prednisone; patients older 65 years old
were given the Alexanian protocol. Response was assessed by
monoclonal protein quantitation, bone marrow plasma cells
percentage and lytic lesions evolution.
RESULTS: Response and survival: Five patients(18,5%) had
obtained complete reponse (CR), 15 (55,5%) patients had partial
response, 7 patients (25,9%) were non responders. Only 4
patients underwent autologous transplantation and 12 patients
were given thalidomide (3 of 5 responders). 8 patients died
(22,8%); patients between 55-60 years aged had higher mortality,
probably because the chemotherapy related toxicity (median age
alive vs died was 62 vs 58); neutropenia infections were the
cause of superior mortality in this group. No death was registered
in patients with melphalan/prednisone, though higher
chemoresistence was observed (40% vs 22%).
Prognosis factors at diagnosis: No significative difference was
observed between outcome and initial evaluated features
(hemoglobin level, platelets cipher, beta-2 microglobulin, renal
failure, state at diagnosis, lytic lesions, tumoral mass, bone
marrow plasma cell percentage, previous treatment and age).
However,poorer responding patients had lower hemoglobin levels
( median 12,5 g/dl in CR vs 9,6 g/dl in NR ) and higher beta-2
microglobulin levels (median 3,5mg/dl in CR vs 8,8 mg/dl in
NR).Supervivence was influence by clinic stage at diagnosis
(11% mortality in IIA stadied patients vs 22% in III-A stage).
CONCLUSIONS: Despite of short following up, high reponse
rate is obtained being thalidomide an effective drug in
maintenance of remission. Patients 55-60 years aged are more
vulnerable to infections in postchemotherapy neutropenia, a cause
of higher mortality; a new i.v. chemotherapy strategy should be
planned for them.
No classic features as renal failure are clearly correlate with
patients outcome. Previously treated patients have the same
probability of response that newly diagnosed patients.
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The diversity of relapse and refractory disease in
multiple myeloma indicates an urgent need for larger
randomized studies of more homogenous populations.
P Gimsing, M Salomo, C Geisler
Rigshospitalet, DK 2100 Copenhagen Ø, Denmark (E-mail:
rhlpgim@rh.dk )
In spite of the improved survival and increased knowledge of the
biology of multiple myeloma all patients will eventually relapse
and later meet the problem of refractory disease to any type of
treatment. The physician of such patients has to meet the
challenge of having to choose between several regimens of
treatment from combination chemotherapy (CCT), a second or
third course of high-dose chemotherapy with stem cell support,
high-dose or continuous steroids, thalidomide and soon newer
treatment principles as IMIDs and proteasome inhibitors. From
reviewing the literature only few randomized studies have been
found and a ‘gold standard’ is missing. Most of the phase II
studies are relatively small and include a heterogeneous
population of relapse, refractory disease, and even some after
multiple treatment regimens including both autologous and
allogeneic transplantations.
The major reason for the lack of help from evidence based studies
is this heterogeneity of the patients. The Mayo clinic
demonstrated the importance of the number of prior treatment
regimens at the recent ASH meeting1, while the Spanish registry
underlines the diversity of relapse after high-dose therapy with
stem cell support 2.
We have looked at the significance of the time for relapse after
stem cell transplantation among our 159 patients who were
treated according to standard condition of the Nordic Myeloma
Study Group3. We found a significant shorter survival after
relapse among patients progressing within the first year of
transplant (median OS 7,5 months, N=21) compared to patients
progressing later (median OS 30,2 months, N=31) (p=0.03).
We therefore request that future studies on the treatment of
relapsing and refractory disease are designed to either unveil the
heterogeneity by narrowing the inclusion criteria e.g. by
including a larger number of centers or by ensuring a stratified
inclusion in randomized studies with enough patients to draw
conclusions for subgroups too.
We recommend that the included patients are as homogenous as
possible with respect to:
Relapse vs. refractory disease
Number of prior treatment regimens
Relapse after high-dose therapy with stem cell support
Time to progression after stem cell transplantation
Pattern of relapse (insidious form, classical form, plasmacytoma
form and the leukaemia form2)
This is an important precondition for informing the patients in a
proper way instead of giving a professional judgment.
Reference List
(1) Kumar S, Larson DR, Therneau TM, Kyle RA, and
Greipp PR. Natural history of relapsed multiple myeloma
[abstract #2352]. ASH. 2002.
(2) Alegre A, Granda A, Martinez-Chamorro C et al.
Different patterns of relapse after autologous peripheral blood
stem cell transplantation in multiple myeloma: clinical results of
280 cases from the Spanish Registry. Haematologica.
2002;87:609-614.
(3) Lenhoff S, Hjorth M, Holmberg E et al. Impact on
survival of high-dose therapy with autologous stem cell support
in patients younger than 60 years with newly diagnosed multiple
myeloma: a population-based study. Nordic Myeloma Study
Group. Blood. 2000;95:7-11.
238
VECD for refratory and resistant multiple myeloma
M.Badea, Daniela Badea
University of Medicine and Pharmacy ,Craiova, Romania
Background. The VAD regimen (infusional vincristine,
doxorubicin and intermittent high-dose dexamethasone) is widely
considered the standard salvage chemotherapy for multiple
myeloma resistant to alkylating agents and is increasingly used
for induction in previously untreated patients prior to high-dose
chemotherapy. VAD chemotherapy needs 4 - days continuous
intravenous (CIV) infusion of vincristine and doxorubicin.
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