Double Transplant Increases Survival in Myeloma Patients

PHILADELPHIA—Final data from a French prospective randomized trial show that high-dose therapy and double autologous transplantation improves survival of younger patients with multiple myeloma.

The results were reported in the plenary session at the 44th Annual Meeting of the American Society of Hematology (abstract 7). 

Michel Attal, MD, reporting for the Intergroupe Francophone du Myelome (IFM), said that double transplant increased 7-year event-free survival to 20% and 7-year overall survival to 42%, twice the results seen in patients randomized to single transplant.

Subgroups most likely to benefit from double transplant include those who fail to achieve at least a partial response after the initial regimen and those who fail to achieve at least a good partial response (defined as more than 90% reduction of the M component on electrophoresis) after the first graft, said Dr. Attal, of the Hopital Purpan, Toulouse.

"After high-dose therapy supported with a single autologous stem cell transplant, almost all patients ultimately relapse," Dr. Attal said. "In order to improve these results, the role of double transplantation has been evaluated in uncontrolled studies, but these cannot be directly compared to the results after single transplant because of selection bias such as age, performance status, and renal function. Our multicenter, prospective, randomized trial was designed to avoid these sources of bias and to compare the effects of single transplant and double transplant."

The investigators enrolled 399 previously untreated myeloma patients under the age of 60 years. Patients were randomized at diagnosis to receive either single transplant or double transplant.

Single transplant patients were prepared with melphalan (140 mg/m²) and total body irradiation (TBI) at 8 Gy. Patients randomized to double transplant were prepared with melphalan alone (140 mg/m²) for the first transplant and with melphalan (140 mg/m²) and TBI (8 Gy) for the second transplant. All patients were initially treated with three to four cycles of vincristine/Adriamycin/dexamethasone (VAD).

78% Had Both Transplants

Dr. Attal said that 85% of patients randomized to single transplant actually underwent transplantation, and 78% of patients randomized to double transplant had both of the planned transplants. Toxic deaths were 5% on both arms, compared with 2% after conventional VAD treatment.

The response rate was not significantly different between the two groups (see Table). Dr. Attal reported that 42% of patients enrolled in the single transplant arm achieved a complete response or a good partial response, compared with 50% of patients enrolled in the double transplant group (P = .15).

With a median follow-up of 75 months, the 7-year postdiagnosis probability of event-free survival was 20% in the double-transplant arm vs 10% in the single-transplant arm (P < .03).

Double transplant produced a notable increase in overall survival. Dr. Attal said that the double-transplant patients had a 42% probability of surviving for 7 years postdiagnosis, while the single-transplant patients had only a 21% probability of surviving that long (P < .01). "However, patients who achieved a good response after the first graft did not have additional benefit from the second one," Dr. Attal said.

Longer survival was associated with a low beta-2-microglobulin level at diagnosis (P < .01), younger age (P < .05), low lactate dehydrogenase (LDH) at diagnosis (P < .01), and randomization to the double-transplant treatment arm (P < .05).

"We conclude that double transplant improves overall survival in multiple myeloma and should be recommended for patients under 60 years of age," Dr. Attal said.