PRIMARY TREATMENT WITH PULSED MELPHALAN, DEXAMETHASONE, THALIDOMIDE (MDT)
FOR SYMPTOMATIC PATIENTS WITH MYELOMA >75 YEARS OF AGE
M.A. Dimopoulos, P. Repoussis, E. Terpos, M.C. Kyrtsonis, A. Zomas, E. Katodritou, S. Delibasi, A. Vassou,
A. Anagnostopoulos, A. Pouli, K. Zervas, D. Margaritis, N. Anagnostopoulos, A. Maniatis,
on behalf of the Greek Myeloma Study Group (GMSG)
BACKGROUND
PURPOSE OF THE STUDY
· Thalidomide is usually administered orally continuously once daily and has shown remarkable activity in
To design a phase II study for the primary treatment of elderly patients (>75 years of age) with MM based on
about 30% of patients with heavily pretreated multiple myeloma (MM). Moreover, there is considerable
intermittent oral administration of melphalan, dexamethasone and thalidomide.
interest in the administration of thalidomide-containing combinations as primary treatment of MM. With such
regimens 60-80% of patients achieve an objective response. Thalidomide can cause a variety of side effects
whose incidence and severity may be related to the maximum dose and duration of thalidomide treatment.
STUDY DESIGN
Furthermore, this drug may be poorly tolerated by older patients.
· Multicenter phase II study initiated in February 2003 which included 50 previously untreated patients >75
· We have previously shown that intermittent administration of thalidomide combined with cyclophosphamide
years of age with symptomatic MM.
and dexamethasone pulses is effective and well tolerated in previously treated patients with MM (MA
· Patients were included regardless of performance status, renal function and comorbidities.
Dimopoulos et al. Hematology Journal, 2004;5(2):112-7
· Palumbo et al recently reported that the combination of melphalan with prednisone and low dose continuous
TREATMENT PLAN
thalidomide induces responses in 93% of previously untreated elderly patients with MM. Deep vein
· Melphalan 8 mg/m2 po days 1-4
thrombosis and especially peripheral neuropathy were significant side effects in this study (A Palumbo et al.
· Dexamethasone 12mg/m2 po days 1-4 and 14-18
Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition) Vol 22, No 14S
· Thalidomide 300 mg po days 1-4 and 14-18
(July 15 Supplement), 2004: 6549)
This regimen is repeated every 5 weeks for 3 courses. Patients without evidence of progressive disease are
scheduled to receive 9 additional courses of MDT (but without DT on days 14-18) every 5 weeks
Assessment of response and progression
PATIENTS' AND DISEASE FEATURES
EBMT criteria , Blade et al, BJH 1998
Patient No
50
· Complete response (CR) was defined as disappearance of the monoclonal protein by immunofixation.
Male/female
29/21
Median age (range)
77 years (75-85)
· Partial response (PR) was defined as >50% reduction in serum monocloncal protein levels and/or >90%
Percent
reduction of the urinary monoclonal protein for at least 6 weeks.
Myeloma Type
IgG
56
· For nonsecretory myeloma, >50% reduction of bone marrow plasma cells or <5% bone marrow plasma
IgA
36
cells were required for partial or complete responses, respectively.
Light chain only
4
IgD
2
· Progression was defined as >25% increase of the serum or urinary paraprotein on at least two occasions,
Non secretory
2
increase in number or size of osteolytic lesions, or development of hypercalcemia.
Performance status
0,1
42
· Patients with CR were considered as progressed in all the above cases and in the case of reappearance of
2,3,4
58
a positive serum or urine immunofixation test
Hemoglobin <8.5 g/lt
14
Calcium >11.5 mg/dl
18
LDH >250 IU
17
ISS
1
10
232
358
1,0
RESPONSE AFTER MTD
TOXICITY AFTER MTD
0,8
percent with
· 44 patients are evaluable so far
Neutropenia (G3,4)
15
· Response assessment was performed on an intent-
Thrombocytopenia (G3,4)
10
0,6
to-treat basis
Somnolence
35
Alive
Constipation
30
PR
27 (61.4%)
Tremor
25
0,4
CR
3 (6.8%)
Xerostomia
15
Total response
30 (68.2%)
Headache
10
0,2
Deep Vein Thrombosis
10
Median time to response:
2 months
Peripheral Neuropathy
10
range:
0.5-14 months
0,0
25 infectious episodes (one fatal)
5
1015
2025
Months
Time to Progression for responding patients
Overall Survival. Three deaths were not
related to myeloma (brain tumor, cerebral
bleeding, non-pathologic hip fracture)
CONCLUSIONS
· This is one of few prospective studies designed specifically for myeloma patients with advanced age (>75 years) i.e. patients who
are not candidates for high-dose therapy and who are frequently excluded from trials.
· The pulsed MTD regimen appears to be a well tolerated and active primary treatment for elderly patients with symptomatic MM.
Responding patients are usually identified early (median time to response: 2 months).
· The incidence of DVT and of peripheral neuropathy appears lower than that seen when thalidomide is administered continuously.

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