Multiple Myeloma: A Practical Guide to Current Management

Multiple Myeloma: A Practical Guide to
Current Management
POSTTRANSPLANTATION MAINTENANCE
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Is posttransplantation maintenance therapy of value
in multiple myeloma?
There were divergent opinions on maintenance therapy
for patients with multiple myeloma. Therapy in this
setting is being actively investigated, and the panel did not
arrive at any consensus regarding the agent(s) of choice
in this setting. In one study [Berenson 2002], alternateday
oral prednisone was evaluated at two dose levels (10
mg or 50 mg) in 250 patients with previously untreated
multiple myeloma following induction chemotherapy
with the VAD regimen. Although treatment-related
adverse events were similar in patients receiving either
10 or 50 mg alternate-day prednisone, the 50-mg dose was
associated with significantly longer progression-free
survival compared to the 10 mg dose (14 months vs. 5
months p=0.003) and median survival (37 months vs.
26 months p=0.05).
The National Cancer Institute of Canada (NCIC):MY-9
was a multi-center, randomized phase II trial that
evaluated the tolerability of combined thalidomide and
prednisone maintenance in multiple myeloma [Stewart
2004]. Patients were eligible if they had received
melphalan 200 mg/m 2 with autologous stem cell
transplants within one year of treatment onset.
Maintenance therapy was initiated within 60 to 100 days
after stem cell transplantation. In the maintenance arms
of the trial, patients were randomized to receive
prednisone 50 mg/day on alternate days and thalidomide
at a dose of either 200 mg/day or 400 mg/day. Therapy
discontinuation or toxicity-associated dose reductions in
thalidomide or prednisone within six months of therapy
initiation were endpoints of the trial. With 67 patients
enrolled and a median follow-up of 36.8 months, the
primary endpoint of the trial was observed in 31% and
64% of patients receiving thalidomide 200 mg/day and
400 mg/day, respectively. After allowing for dose
reduction, 76% and 41% of patients receiving
thalidomide 200 mg/day and 400 mg/day, respectively,
remained on any maintenance therapy 18 months after
registration. Dose reductions in thalidomide and
prednisone were observed in 88% and 72% of patients,
respectively, within two years of initiating maintenance
therapy. This trial established an appropriate dosing
schedule for phase III trials, utilizing the thalidomide
200 mg/day.
The Intergroupe Francophone du Myelome (IFM) 99 02
[Attal 2005] is the first trial evaluating the impact
of maintenance treatment with thalidomide on the
duration of response obtained after high-dose therapy.
Multiple myeloma patients (under 65 years at diagnosis)
with no or with only one adverse prognostic factor
(β 2 -microglobulin >3 mg/L or deletion of chromosome
13) were enrolled in the trial. Patients were treated with
the following:
• Three to four cycles of the VAD regimen;
• A first autologous transplantation after preparation with
melphalan 140 mg/m 2 ;
• A second autologous transplantation after preparation
with melphalan 200 mg/m 2 .
Patients without progressive disease three months
after the second transplantation were randomized to Arm
A (no maintenance treatment), Arm B (maintenance
treatment with pamidronate 90 mg/month), or Arm C
(maintenance treatment with thalidomide 100 mg/day
and pamidronate 90 mg/month). Updated data as of April
2005 are summarized in Table 4. The mean follow-up
from diagnosis was 36 months. Conclusions from this
trial are that thalidomide is an effective maintenance
therapy that prolongs duration of response after high
dose therapy and that pamidronate is effective
maintenance to decrease the incidence of bone events in
these patients.
Because there are no definitive data from phase III
clinical trials, routine maintenance therapy is not
currently recommended until current clinical studies
mature.