NANTES, FranceAs the conditioning regimen for autologous
transplantation in multiple myeloma, high-dose melphalan (Alkeran)
200 mg/m² is as effective as, but less toxic than, melphalan 140
mg/m² plus total body irradiation. This approach should be
considered as the standard conditioning regimen, French investigators
contended at the ASH meeting.
Jean-Luc Harousseau, MD, of the University Hospital Hotel-Dieu,
Nantes, France, presented preliminary results from a 42-center study
of 442 patients age 65 and younger with newly diagnosed multiple
myeloma. The patients were randomized to high-dose melphalan 140
mg/m² plus total body irradiation (TBI) with 8 Gy, or
higher-dose melphalan 200 mg/m² alone (HDM200).
Patients first received three cycles of vincristine, Adriamycin , and
dexamethasone (VAD), then underwent collection of peripheral blood
progenitor cells (PBPC) after priming with G-CSF alone or with
cyclophosphamide (Cytoxan, Neosar) plus growth factors. At the time
of PBPC harvest, patients were randomly assigned to one of the two
conditioning regimens, followed by PBPC autologous transplantation.
The analysis included 221 evaluable patients. The two treatment
groups were well balanced for initial characteristics, response to
VAD, type of PBPC mobilization, and growth factors. Median number of
CD34+ cells in the graft was slightly higher in the TBI group.
Hematologic toxicity for the HDM200 group was significantly less than
for the TBI group (see Table 1).
For extra-hematologic toxicity, the only significant difference was
the incidence of grade 3 or higher mucositis (51.5% after TBI versus
29.5% after HDM200; P = .003). There was also more pulmonary and
cardiac toxicity with TBI.
There were no toxic deaths with HDM200, but, perhaps because of
higher toxicity, four toxic deaths occurred with TBI. The difference
was not statistically significant. Clinical outcomes were not
significantly different for the two regimens, including percentage of
complete remissions (30% for TBI and 33% for HDM200) or complete
remissions plus very good partial remissions (41% for TBI and 53% for HDM200).
At a median follow-up of 26 months, median event-free survival was 22
months for TBI and 18 months for HDM200 (not significant). There were
no significant differences in 2-year event-free survival (20 months
for HDM200 and 30 months for TBI) or overall survival at 26 months
(70% for HDM200 and 80% for TBI), Dr. Harousseau reported.
We concluded there is no significant difference in outcome
between these regimens, but the hematologic and extrahematologic
toxicities are lower with high-dose melphalan 200. We feel that
high-dose melphalan alone should be the standard conditioning regimen
for autologous transplantation in patients with newly diagnosed
multiple myeloma, and in future protocols we will abandon total body irradiation.
Since high-dose melphalan 200 is well-tolerated, the investigators
have explored higher doses and have shown that 220 mg/m² is
feasible, the only adverse event being a high incidence of severe
mucositis. A new strategy that combines high-dose melphalan 220
mg/m² with anti-interleukin-6 and dexamethasone, has had
very encouraging results in 18 relapsed patients, Dr.