Randomized trial of ?-interferon or dexamethasone as maintenance treatment for multiple myeloma

Abstract

In order to assess the role of alpha-interferon or dexamethasone as maintenance therapy for multiple myeloma, 172 consecutive, previously untreated patients with disease of low or intermediate tumor mass received primary therapy with oral melphalan and intermittent, high-dose dexamethasone (MD), repeated monthly. Within 5 months, 84 responding patients were assigned at random to maintenance treatment with alpha-interferon (3 mU s.c. 3 x weekly) or dexamethasone (20 mg/m2 p.o. each morning for 4 days) repeated monthly until relapse. Upon relapse, MD was resumed for 2 cycles and second responses were maintained with 4-day courses of melphalan-dexamethasone until second relapse. Initial response was achieved in 88 patients (51%) after a median 0.7 month and no more than 3 courses of MD, a frequency of response similar to that observed previously with dexamethasone alone. There were identical median remissions of 10 months with interferon or dexamethasone, both maintenance regimens being associated with infrequent, mild, and reversible side effects. Significantly more patients responded again to resumption of MD after disease relapse to interferon (82%) than to dexamethasone (44%) (P = 0.001). The median remission from randomization to melphalan-resistant second relapse was 32 months for patients maintained initially on interferon compared to 19 months for those on dexamethasone (P = 0.01). These findings supported an advantage for interferon in remission maintenance by increasing the frequency of tumor recontrol with later treatment that included dexamethasone.

Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients

“…19,20 Since maintenance interferon does not improve outcome, this benefit may be observed with the use of glucocorticoids alone. Although pulse dexamethasone produced a similar outcome to 3-times-a-week interferon maintenance therapy among patients responding to MD induction therapy, 21 the type and length of induction therapy (melphalan-containing compared with VAD-like regimens) and the type, dose, and schedule of steroids may be critical to their efficacy during maintenance therapy. In fact, patients received only a median of 2.5 months (maximum, 4.9 months) of induction MD therapy, 21 and this short induction period is unlikely to be long enough to produce a maximal antimyeloma effect with the use of a melphalan-based regimen.…”

“…Recently, the MD Anderson group (Houston, TX) randomized 84 patients responding to intermittent oral melphalan and high-dose oral dexamethasone (MD) to maintenance treatment with either ␣-interferon (3 mIU subcutaneously 3 times weekly) or pulse oral dexamethasone (20 mg/m 2 for 4 days monthly) until relapse. 21 Importantly, among patients randomized to maintenance treatment, the duration of induction therapy was limited to a median of only 2.5 months. Although there was no difference in duration of response or overall survival between the 2 maintenance treatments, the authors showed that more patients responded to resumption of MD treatment following relapses from interferon (82%) compared with dexamethasone (44%) maintenance treatment.…”

Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

“…A study by Alexanian et al did randomize patients treated initially with melphalan and intermittent, high-dose dexamethasone to receive maintenance with either α-interferon or dexamethasone. 51 Both regimens resulted in similar median remission durations of 10 months, though patients who received interferon had a higher likelihood of responding to MD if this was reinstituted at the time of relapse, suggesting a possible benefit for interferon. However, when interferon-α-2b was studied as a maintenance regimen in a randomized fashion compared with observation alone in patients initially treated with MP, a benefit was not seen.…”

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

“…Complete response rate has historically correlated poorly with overall survival (Baldini 1991;Riccardi et al, 2003;Durie et al, 2004), and clearly does not take account of quality of life aspects, which are affected by increasingly prolonged myeloma therapy regimens. In early trials, time to progression did correlate with overall survival, but with consolidation treatment this association is no longer seen (Alexanian et al, 2000;Attal et al, 2012;Maiolino et al, 2012;Sonneveld et al, 2012;Stewart et al, 2013). PFS2, the time from first treatment to second relapse, takes account of tumour resistance induced by the first line of treatment, and to date studies have shown it is prolonged in association with PFS (Palumbo et al, 2014b;Tacchetti et al, 2014), but it has not yet been validated as a surrogate for OS, and still takes years of follow up to report mature data.…”

“…A therapeutic dose of prednisolone conferred a survival benefit when used after VAD-based conventional chemotherapy (Berenson et al, 2002) but glucocorticoids as monotherapy in the post-ASCT population are redundant now given the improved clinical activity and tolerability observed with IMiDs and proteasome inhibitors. In a phase III comparison between dexamethasone and interferon maintenance, the dexamethasone group responded very badly to melphalan/dexamethasone at relapse, presumably due to selection of resistant clones (Alexanian et al, 2000).…”