Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies.
BACKGROUND
Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification.


METHODS
256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials.


RESULTS
The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance.


CONCLUSIONS
Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.
Ludwig
H
H
1st Department of Medicine and Oncology, Wilhelminenspital, Vienna, Austria.
Cohen
A M
AM
Polliack
A
A
Huber
H
H
Nachbaur
D
D
Senn
H J
HJ
Morant
R
R
Eckhardt
S
S
Günczler
P
P
Seewann
H L
HL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage; D011994:Recombinant Proteins; D012074:Remission Induction; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014750:Vincristine; D003520:Cyclophosphamide; D008558:Melphalan; D011241:Prednisone