Double Autologous Transplantation Improves Survival of Multiple Myeloma Patients: Final Analysis of a Prospective Randomized Study of the "Intergroupe Francophone du Myelome" (IFM-94).

Reviewer: Tracy d'Entremont, MD
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Last Modified: December 8, 2002

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Presenter: Michel Attal
Presenter's Affiliation: Hopital Purpan; Toulouse, France
Type of Session: Plenary

Background

  • Multiple Myeloma has been a challenging disease with little change in the Median Survival (MS) in the past 20 years; MS averages 30-36 months.
  • With the introduction of high dose chemotherapy with autologous stem cell transplantation, there have been reports from single institutions, case-controlled and randomized studies of CR of 40%.
  • Unfortunately, most of these patients are still at risk for relapse and the 7-year event free survival (EFS) is only 10%.
  • In order to improve these results, double transplantation (DT) has been evaluated in uncontrolled studies.
  • This is a multicenter, prospective randomized trial designed to compare the results of single transplant to DT for multiple myeloma.

Materials and Methods

  • From October 1994 to March 1997, 399 untreated myeloma patients, under the age of 60, were randomized at the time of diagnosis to one of 2 arms:
    ST with the following preparative regimen: Melphalan 140mg/m2 + TBI (8 Gy)
    DT with a melphalan alone initial preparative regimen for the 1st transplant followed by Melphalan 140mg/m2 + TBI for the 2nd transplant.
  • All patients were initially treated with VAD for 3 cycles prior to stem cell harvesting.

Results

  • The results reported were on an intention to treat basis and represent a median follow-up of 70 months.
  • The response rates were similar in both arms:
    42% of ST patients achieved CR or very good partial response (VGPR) which was defined as mort than 90% reduction of the M component on electrophoresis
    50% of the DT patients achieved CR or VGPR (p=0.15)
  • However the 7-yr EFS was significantly better in the DT arm (20% vs. 10%; p<0.03)
  • The 7-yr Overall Survival was also higher in the DT arm (42% vs. 21%; p<0.01)
  • 4 factors were found to be associated with a longer survival:
    low beta-2-microglobin at diagnosis (p<0.01)
    young age (p<0.05)
    low LDH at diagnosis(p<0.01)
    DT vs ST (p<0.05)
  • Further analysis lead to differentiation of two subgroups of patients who tended to have a higher chance of benefiting from DT:
    patients who achieved less than 50% RR after VAD therapy
    patients not acheiving a VGPR after the first transplant.

Author's Conclusions

  • DT improves the EFS and OS at 7 years in patients under the age of 60 with multiple myeloma.
  • This regimen should be offered to patients and in particular to those patients failing to achieve a PR after VAD or failing to achieve a VGPR after ST.

Clinical/Scientific Implications

    Despite the introduction of melphalan and high dose therapy to the treatment of multiple myeloma, long term survival is rare. This study from France provides evidence that double transplant is feasible in patients under age 60 without significant increase in toxicity. The subset of patients they identified who seem to benefit from DT are the ones who have failed conventional therapy. It would be helpful to be able to identify additional patients who may be at high risk of relapse after ST perhaps through genetic profiling.

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