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

European Journal of Haematology 86 (16–22) Addition of thalidomide to oral melphalan/prednisonein patients with multiple myeloma not eligible fortransplantation: results of a randomized trialfrom the Turkish Myeloma Study Group Meral Beksac1, Rauf Haznedar2, Tulin Firatli-Tuglular3, Hakan Ozdogu4, Ismet Aydogdu5, NahideKonuk1, Gulsan Sucak2, Is¸ık Kaygusuz3, Sema Karakus4, Emin Kaya6, Ridvan Ali7, Zafer Gulbas8,Gulsum Ozet9, Hakan Goker10, Levent Undar11 1Department of Hematology, Faculty of Medicine, Ankara University, Ankara; 2Department of Hematology, Faculty of Medicine, Gazi University,Ankara; 3Department of Hematology, Faculty of Medicine, Marmara University, Istanbul; 4Bas¸kent University, Adana Practice and Research Center, Adana; 5Department of Hematology, Faculty of Medicine, Selc¸uk University, Konya; 6Department of Hematology, Faculty of Medicine, _Ino¨nu¨ University, Malatya; 7Department of Hematology, Faculty of Medicine, Uludag˘ University, Bursa; 8Department of Hematology, Faculty of Medicine, Osmangazi University, Eskis¸ehir; 9Department of Hematology, Ankara Numune Hospital, Ankara; 10Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara; 11Department of Hematology, Faculty of Medicine, Akdeniz University, Antalya, Turkey The combination of melphalan–prednisone–thalidomide (MPT) has been investigated in several clinicalstudies that differed significantly with regard to patient characteristics and treatment schedules. This pro-spective trial differs from previous melphalan–prednisone (MP) vs. MPT trials by treatment dosing, dura-tion, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiplemyeloma (MM) (n = 122) aged greater than 55 yr, not eligible for transplantation were randomized toreceive 8 cycles of M (9 mg ⁄ m2 ⁄ d) and P (60 mg ⁄ m2 ⁄ d) for 4 d every 6 wk (n = 62) or MP and thalido-mide (100 mg ⁄ d) continuously (n = 60). Primary endpoint was treatment response and toxicities following4 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 renalimpairment (RI, 19% vs. 7%, respectively; P = 0.057). After 4 cycles of treatment (n = 115), there weremore partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P = 0.030). How-ever, 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 ofgrade 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 thefirst 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 fre-quent RI, better responses and less early mortality were observed in all age groups despite more frequentdiscontinuation. This study is registered at http://www.clinicaltrials.gov as #NCT00934154.
Key words multiple myeloma; treatment; melphalan; prednisone; thalidomide

Source: http://www.multiplmiyelom.org/files/tmsg/AVSCFR6.pdf