Haematologica 2003 - Supplements

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Melphalan and Dexamethasone- Is it choice of therapy
in Patients not willing for ABMT in Multiple Myeloma ?
Sharma A, Raina V, Bedi N, Kumar R, Mohanti B K,
Kochupillai V
Institute Rotary Cancer Hospital, All India Institute of Medical
Sciences, New Delhi, India
Multiple myeloma (MM) is conventionally treated with
combination chemotherapy using oral melphalan, prednisolone (
MP) or infusional vincristine, adriamycin, and dexamethasone
(VAD) followed by autologous bone marrow/ stem cell
transplant ( ABMT). Even though VAD doesn’t offer any
survival advantage it is preferred because of less stem cell
toxicity and faster responses. The faster response with VAD
regimen is because of dexamethasone. For patients who are not
candidates for autologous transpalnt combination of melphalan
and dexamethasone (MD) may be a good oral alternative to MP
or VAD if it results in comparable responses and time to
responses. It is all the more important for country like us where
many patients are unable to bear cost of VAD. From November
2000 to September 2002, 22 newly diagnosed patients who were
not willing to undergo ABMT, were enrolled onto this study.
Patients characteristics: Median age- 55 years ( 27-75 years),
Sex- males 12, Stage distribution- IIIA- 16, and IIIB- 6 patients.
Sixteen patients had bone marrow plasma cells > 25%.
Monoclonal band – IgG –13, IgA- 2, pure light chain myeloma-
7 patients. Beta 2 microglobulin was done in 13 patients and it
was high in 9. Treatment – melphalan 6 mg/m 2 PO day 1-4,
dexamethasone 40 mg PO day 1-4 and 9-12 every 4 weeks with
PCP prophylaxis using Septran. Therapy was discontinued if;
patient became intolerant, disease progressed, or 12 cycles were
completed in responding patients. Results- results are shown in
table 1. Two patients achieved CR after 2 cycles.
Response
n=22
CR PR SD PD Non evaluable
(LFU before
assessment)
5 9 4 0 4
After 4
cycles
Best 6 8 4 0 4
response
Toxicity- Treatment was generally well tolerated, still,
dexamethasone was stopped in 3 patients because of proximal
myopathy. Survival- Currently 5 patients are alive without
evidence of disease, 10 are surviving with disease, 6 have died of
disease progression, and in 1 patient follow up information is not
available. Median survival has not reached. Two years OS and
PFS is 63% and 70% respectively. Conclusion- Combination of
melphalan and dexamethasone is safe, may be effective oral
alternative to infusional VAD in patients not willing to undergo
ABMT, and probably superior to MP in time to responses. We,
plan to start a randomised trial between MP and MD in patients
not willing for ABMT.
235
A 15 years experience in the treatment of multiple
myeloma patients with conventional chemotherapy –
the end of one era?
J.Bila, I.Elezovic, D.Tomin, M.Gotic, N.Suvajdzic,
M.Sretenovic, V.Cemerikic, D.Boskovic.
Institute of Haematology, Clinical Center of Serbia, Belgrade,
Serbia.
Despite all the advances in systemic and supportive therapies,
multiple myeloma (MM) is still currently an incurable plasma
cell malignancy.The aim of study was to present results of a longterm
follow up (15yrs) of MM patients treated with conventional
chemotherapy followed with Interferon-Alpha (IFN-a)
maintenance therapy.
Patients and methods: The study included 120pts with de novo
diagnosed MM between 1988 and 2003. The group consisted of
63 male and 57 female pts, mean age 65yrs (range 27-79).
According to the clinical stage (CS) of disease, distribution of
MM pts was as follows: I 8pts (6,7%), II 44pts (36,7%), III 68pts
(56,7%). Renal impairment existed in 29pts (24,2%). There were
48pts (40%) with IgG kappa monoclonal (M) protein, 36pts
(30%) with IgG lambda, 22pts (18,3%) with IgA, 2pts (1,7%)
with IgD, and 12pts (16%) with secretion of kappa/lambda light
chains. None secretory MM was diagnosed in 4pts (3,3%).
Elevated Beta2-microglobulin was registered in45/60 analyzed
pts (75%). Imunohistochemical staining of bone marrow revealed
high expression of VEGF, BFGF and Ki-67 in 20/45 analyzed pts
(44,4%).
Results: Chemotherapy according to the MP/VMCP regimen was
applied through 2-15 cycles (Me 9) at 100pts (83,3%) as the
initial MM treatment. Plateau phase was achieved in 55pts (55%)
with duration 1-90m (Me 21). During plateau phase, 65/100pts
(65%) relapsed and therefore were treated with second line
regimen (VAD,M2, Z-Dex). The overall survival for this group of
MM pts was 1-142m (Me 42) with five-year survival obtained in
20% of MM pts.Two pts (2%) died due to secondary malignancy.
Twenty MM pts (16,7%) in the II and IIICS with renal
impairment were treated with 2-9 cycles (Me 6) of VAD
protocol. Five pts (25%) died during the treatment. Responses
according to the EBMT/IBMTR criteria were as follows: 3/15
complete responses (20%), 9/15 partial responses (65%), 2/15
minimal responses (13,3%) and 1/15 stable disease (6,7%).
Average duration of remission was 18m (7-29). Relapses were
observed in 10/15pts (66,7%). Median overall survival (24m) was
similar to the survival of MM pts treated with MP/VMCP
protocol. During plateau phase 29pts (24,2%) received IFN-a
maintenance therapy which resulted with evidently longer
duration of plateau phase compared to MM pts without IFN-a
therapy (Me 21m vs. Me15m).
Conclusion: Treatment results of different chemotherapy
protocols for MM, followed by IFN-a maintenance therapy, are
very similar and not satisfactory.
Is it the end of one era? A great improvement is achieved
applying high-dose therapy with stem-cell support, but without
definitive curable effect. New treatment options which target is
the MM cell, the MM cell-host interaction offers a great promise
to improve patient outcome in MM.
236
A NEW PROTOCOL OF MULTIPLE MYELOMA:
RESULTS OF A PRELIMINARY EVALUATION.
Puertas A, Montero I, Martino ML, Campo T, Vaquero A,
Parody R, Rodriguez ,JM
Division of Haematology. University Hospital "Virgen del Rocío".
Seville (Spain).
INTRODUCTION: Multiple myeloma (MM) is a clonal plasma
cell proliferative disorder that accounts for 10% of malignant
hematologic neoplasms. Combinations of different chemotherapy
regimens have not improved survival significantly in relation
with the combination of melphalan-prednisone. Others alternative
treatments as autologous stem cell transplantation, thalidomide
and inmunotherapy have been proposed. We followed up a group
of 35 patients with active MM treated with a novel total therapy
protocol during a two years period.
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