Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial.
OBJECTIVE
The Dutch-Belgian HOVON group performed a randomized phase 3 trial to compare single non-myeloablative intensive treatment with double, intensive treatment in previously untreated patients with multiple myeloma (MM).


METHODS
Three hundred and three patients with stage II/III MM were randomized after VAD induction chemotherapy to receive two cycles of non-myeloablative intermediate-dose melphalan (70 mg/m2) (single treatment) or the same regimen followed by cyclophosphamide 120 mg/kg iv plus total body irradiation (TBI) 9 Gy and autologous stem cell transplantation (double, intensive treatment). In both treatment arms interferon .IIa was given as maintenance until relapse/progression.


RESULTS
A significantly higher proportion of patients achieved a complete remission (CR) on protocol treatment with double, intensive therapy (32 % vs 13 %, p<0.001). Double treatment produced better outcome in terms of event-free survival (median 22 vs 21 months, 28% vs 14% at 4 years and 15% vs 7% at 6 years after randomization; logrank p=0.013; univariate HR 0.74, 95% CI, 0.58-0.94), progression-free survival (median 27 vs 24 months, 33% vs 16% at 4 years, and 17% vs 9% at 6 years after randomization; logrank p=0.006; HR=0.71, 95% CI 0.56-0.91), but not overall survival (median 50 vs 55 months, 52% vs 56% at 4 years and 39% vs 36% at 6 years after randomization; logrank p=0.51; HR=1.10, 95% CI 0.83-1.46). The achievement of a CR had a favorable prognostic impact on event-free survival (HR=0.60 , 95% CI=0.44 -0.82 , p=0.001) and progression-free survival (HR=0.62 , 95% CI=0.45 -0.84, p=0.002).


CONCLUSIONS
Double, intensive treatment resulted in a better CR rate, event-free survival and progression-free survival but not overall survival compared to single non-myeloablative treatment in previously untreated patients with multiple myeloma.
Sonneveld
Pieter
P
Erasmus Medical Center Rotterdam, The Netherlands. p.sonneveld@erasmusmc.nl
van der Holt
Bronno
B
Segeren
Christine M
CM
Vellenga
Edo
E
Croockewit
Alexandra J
AJ
Verhoe
Gregor E G
GE
Cornelissen
Jan J
JJ
Schaafsma
Martijn R
MR
van Oers
Marinus H J
MH
Wijermans
Pierre W
PW
Westveer
Petra H M
PH
Lokhorst
Henk M
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D005500:Follow-Up Studies; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D009426:Netherlands; D012074:Remission Induction; D016019:Survival Analysis
D019653:Myeloablative Agonists; D008558:Melphalan