Thalidomide-Dexamethasone vs. Melphalan-Prednisone as First Line Treatment and Thalidomide-Interferon vs. Interferon Maintenance Therapy in Elderly Patients with Multiple Myeloma.

Thalidomide-Dexamethasone (TD) is an active regimen both in patients (pts) with relapsing/refractory and in untreated pts with multiple myeloma (MM). Here we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly pts with MM. 274 pts have been enrolled (median age: 72 yrs, stage I: 9 (3%), stage II: 84 (31%), stage III: 179 (65%). Pts were randomized to T 200mg/day and D 40mg, days 1–4 and 15–18 (on odd cycles) and days 1–4 (on even cycles) or M 0.25mg/kg days 1–4 and P2mg/kg days 1–4, q 4–6 weeks. T should be dosed up to 400mg/day, if feasible. Pts achieving response or SD were randomized to maintenance therapy either with T (≤200mg/day)-Interferon-a2b (IFN, 3Mega U, TIW) or IFN (3Mega U/TIW). Zoledronic acid (4mg) was administered monthly to all pts during the entire treatment period. Response is defined according Blade’s criteria, plus nCR defined as IF positive or >90%↓ in PP and VGPR defined as >75% ↓reduction in PP. 231 pts are evaluable per protocol. Best response to TD: CR (14%) nCR 17%, VGPR 17%, PR 21%, yielding an ORR (CR-PR) of 68%. Best response to MP: CR 7%, nCR 8%, VGPR 14%, PR 22%; ORR 51% (ORR in TD vs. MP p=.0044). Time to response and time to best response were shorter in the TD (6, 16 weeks, respectively) compared to the MP group (16, 25 weeks, respectively; p<.001, p<.002, respectively).There was a tendency for more early treatment discontinuations in the TD arm (15 vs. 11, p=.416) and a higher mortality during the first treatment year (31 vs. 17, p=.026). Pts treated with MP showed a tendency for longer EFS (median: 43 vs. 25mos; p<.07) and had sign. longer OS compared to those on TD (median: 58 vs. 45mos;p=.029). A retrospective comparison of pts ≤ aged 72 showed no difference in OS (median: 57.9 vs. 50 mos, p<.186) but OS was longer in pts >72 yrs treated with MP (median: 46.5.9 vs. 25.4, p<.0625). Maintenance treatment in the 108 pts randomized to either T-IFN, or IFN only, did not result in a sign. difference in OS (from start of maintenance: not reached vs. 41.1 mos, p<.95). Pts on MP had a higher incidence of G 3–4 leucopenia (14% vs. 3%; p< .0001), while for thrombocytopenia only a tendency for a higher frequency was noted. Pts on TD had more G 2–3 neuropathy (28% vs. 10%, p<.001), constipation (30% vs. 10%, p<.001), psychological toxicity (18% vs. 6%, p<.0006), and a tendency for a higher rate of skin toxicity (9% vs. 5%, p=.069), and infections (23% vs. 16%, p<.12) compared to those on MP. The cumulative incidence of DVTs was 15% in pts on TD and 6% in those on MP (p=.089). In conclusion, TD treatment resulted in sign. higher rate of CR/nCR and ORR, a sign. shorter time to response and to best response. Pts on TD had similar EFS but sign. shorter OS. This was particularly true in pts aged >72 years but not in those aged ≤72 who showed similar OS with TD and MP. Pts on TD had more neuropathy, DVT, psychological toxicity, and a higher rate of early treatment discontinuations, while haematological toxicity was higher in pts treated with MP.