To the Editor:

The role of interferon maintenance treatment in patients with multiple myeloma (MM) is still debated. In 1990, the Italian Multiple Myeloma Study Group published the results of the first randomized study on the role of interferon a2-b (IFN) as maintenance treatment in patients responding to induction therapy.1 One hundred one MM patients responding to traditional first-line induction chemotherapy were randomized to receive (n = 50) or not receive (n = 51) IFN maintenance. Patients were recruited from a group of 202 symptomatic MM patients observed in the three university institutions of Rome, Bari, and Turin, Italy. The results originally demonstrated that a maintenance treatment with IFN prolonged response and survival duration in patients with MM who have responded to conventional induction therapy.

After this experience, five large randomized studies were published comparing IFN maintenance versus untreated control: two of them did not demonstrate any advantage as for response and survival duration2,3; one showed a clear advantage in response duration but not in survival duration4; and two demonstrated a significant improvement both in response duration and in survival duration.5 6 

The updated results of the Italian study 9 years after the randomization of the last patient confirm a significant prolongation of response duration in IFN maintained patients: the median response duration (from time of randomization to maintenance treatment) is 24 months in patients receiving IFN and 13 months in untreated patients (P = .0016). The results in terms of prolongation of survival are less significant: the median overall survival is of 50 and 39 months, respectively (P = .21); among patients who had an objective response to induction chemotherapy (>50% reduction in M protein), the median survival was 50 and 35 months, respectively (P = .07; Fig 1). However, 9 patients are still alive and in response in the IFN-maintained group versus 2 in the unmaintained group.

Fig. 1.

Kaplan-Meier curves for response and survival after randomization of patients to the interferon maintenance group or control group.

Fig. 1.

Kaplan-Meier curves for response and survival after randomization of patients to the interferon maintenance group or control group.

Close modal

In conclusion, the majority of randomized studies on IFN maintenance in MM as well as our results demonstrate that IFN maintenance significantly prolongs the response duration phase in MM patients responsive to previous induction therapy, whereas the efficacy on survival prolongation is less clear. Despite the uncertain effect on survival duration, IFN maintenance is still appropriate in responding myeloma patients, because delaying relapse appearance allows a higher quality of life in patients with MM. Nevertheless, accurate quality of life evaluation is required in these patients to confirm this assumption.

1
Mandelli
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VM
Marmont
F
Petrucci
MT
Tribalto
M
Vegna
ML
Dammacco
F
Pileri
A
Maintenance treatment with recombinant alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy.
N Engl J Med
322
1990
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2
Peest
D
Deicher
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Coldewey
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Leo
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Bartl
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Bartels
H
Braun
HJ
von Broen
IM
Fisher
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Gramatzky
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Hein
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Kreuser
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Meier
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Oertel
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Selbach
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Melphalan and prednisone (MP) versus vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAM Dex) induction chemotherapy and interferon maintenance treatment in multiple myeloma.
Onkologie
13
1990
458
3
Salmon
SE
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JJ
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Pugh
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B
Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: A South West Oncology Group Study.
J Clin Oncol
12
1994
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4
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Roedjer
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I
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Hajorth
M
Zador
G
Interferon alfa-2b versus no maintenance therapy during the plateau phase in multiple myeloma: A randomized study.
Br J Haematol
89
1995
561
5
Browman
GP
Bergsagel
D
Sicheri
D
O’Reilly
S
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KS
Rubin
S
Belch
A
Shustik
C
Barr
R
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I
James
K
Zee
B
Johnston
D
Randomized trial of interferon maintenance in multiple myeloma: A study of the National Cancer Institute of Canada clinical trials group.
J Clin Oncol
13
1995
2354
6
Ludwig
H
Cohen
AM
Polliak
A
Huber
H
Nachbaur
D
Senn
HJ
Morant
R
Eckhardt
S
Gunczler
P
Seewann
HL
Shuller
J
Rheiner
K
Cavalli
F
Fritz
E
Interferon alpha for induction and maintenance in multiple myeloma: Results of two multicenter randomized trials and summary of other studies.
Ann Oncol
6
1995
467
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