SEATTLE--French researchers have recently concluded a study of
multiple myeloma in which high-dose chemotherapy combined with
autologous bone marrow transplantation (HDC/ABMT) resulted in
a significant improvement in response rate and overall survival,
compared with conventional chemotherapy.
Michel Attal, MD, PhD, head of the Bone Marrow Transplantation
Unit, Purpan Hospital, Toulouse, presented the study results at
the American Society of Hematology's 37th Annual Meeting.
Dr. Attal said that conventional chemotherapy for multiple myeloma
has proved disappointing, with a median overall survival rate
of only 2 to 3 years and few, if any, complete remissions.
To improve these results, a high-dose chemotherapy regimen using
melphalan (Alkeran) was developed for the treatment of aggressive
multiple myeloma, and has been anecdotally reported to induce
an improved response, including some complete remissions, in patients
refractory to conventional dosages. This improved response was
achieved at the expense of serious myelotoxicity, but use of ABMT
has reduced this toxicity.
A direct comparison of this method with that of conventional treatment
modalities has not previously been possible, due to patient selection
bias (including young age and normal renal function), Dr. Attal
said. The 5-year prospective trial, conducted by the Intergroupe
Français du Myelome (IFM 90) in Toulouse, was designed
to remove this selection bias.
At diagnosis, 200 patients under age 65 with intermediate or high
tumor mass (stage II/III DS), previously untreated multiple myeloma
were randomized to receive either a conventional chemotherapeutic
regimen of VMCP/BVAP or high-dose therapy, consisting of melphalan
(140 mg/m²) and total body irradiation, supported with unpurged
autologous bone marrow, collected after two cycles of VMCP/BVAP.
Maintenance with alpha-interferon was used in both arms.
The response rate was significantly better in the high-dose arm
(22% complete response) than in the conventional arm (5%) (P less
than .001). For the category of "very good partial response"
(ie, greater than 90% response), the numbers were 16% vs 9%, respectively.