Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group

Abstract

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n=122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m(2) /d) and P (60 mg/m(2) /d) for 4d every 6 wk (n=62) or MP and thalidomide (100 mg/d) continuously (n=60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P=0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P=0.057). After 4 cycles of treatment (n=115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P=0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P=0.655; DFS 21.0 vs. 14.0 months, P=0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P=0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n=8, 14.0%) than in the MPT arm (n=2, 3.4%; P=0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P=0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation.

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

“…Six randomized studies have compared MPT with melphalan, prednisone (MP) [70][71][72][73][74][75]. An OS advantage has been observed in three trials [70,71,74].…”

Management of older adults with multiple myeloma

“…35 In two other trials performed by the Nordic and Turkish groups, ORR was higher in patients who were given thalidomide, but this advantage did not translate into longer PFS and OS in comparison with those who did not receive thalidomide. [36] and [37] An efficacy meta-analysis of the six MPT trials including 1685 patients was conducted ( Table 2). 15 Despite the heterogeneity of the trials, both for patient characteristics and thalidomide schedules (dose and duration of treatment), the addition of thalidomide to MP significantly prolonged both PFS and extended OS by 20% (6.6 months) compared to MP.…”

Advances in treatment for newly diagnosed multiple myeloma patients ineligible for autologous stem cell transplantation

“…8 In the IFM01-01 study, conducted in 232 very elderly patients (aged 475 years), median OS was significantly longer in patients treated with MPT compared with MP alone (44.0 versus 29.1 months; HR ¼ 0.68; P ¼ 0.028). 9 A borderline significant improvement in OS for MPT versus MP was also reported by the Dutch-Belgium HematoOncology Cooperative Group in the HOVON-49 study ( 15 ) failed to show a persistent survival advantage with MPT. A meta-analysis of the six randomized trials of MPT versus MP (three of which included thalidomide maintenance therapy) has identified that the addition of thalidomide to MP as a frontline regimen in elderly NDMM patients significantly prolongs both PFS and OS by around 6 months compared with MP.…”