Thalidomide-dexamethasone versus melphalan- prednisolone as first line treatment in elderly patients with multiple myeloma: Second interim analysis

Background: Thalidomide-dexamethasone (TD) is an active regimen both in patients with relapsing/refractory and in previously unreated patiens with multiple myeloma. Aims: In the present trial we compare TD with standard melphalan-prednisolone (MP)inpreviously untreated eldery patients with multiple myeloma. Methods: 276 patients have been enrolled so far (median age: 72 y.o., stage I: 12(4%), stage II 91 (33%), stage III: 173 (63%). Patients are randomized to thalidomide 200mg/day and dexamethasone 40mg, days 1-4 and 15-18 (on odd cycles) and days 1-4 (on even cycles) or melphalan 2, 5mg/kg day 1-4 and prednisone 2mg/kg days 1-4, q4-6 weeks. Thalidomide should be dosed up to 400mg/day if feasible. Patients achieving response or stabilization are randomized to maintenance treatment either with thalidomide (max dose 200mg/day)-INFalpha2b (3 MegaU, TIW) or INFalpha2b (3 MegaU/TIW). All patients are scheduled for monthly Zometa(4mg) during the entire period. Response is defined according Blade's criteria, plus nCR defined as IF positive CR and VGPR defined as >90% reduction in PP. Statistical results are given by intend to treat and per protocol analysis. Results: 197 patients are evaluable for response as yet. Best response to TD was: CR 7(7%), nCR 20(21%), and VGPR 13(14%), PR 16(17%), MR 10(10%) yielding an ORR (CR-PR) of 58%. The respective results in patients on MP were: CR 4(4%), nCR 10(10%), and VGPR 11(11%), PR 25(25%), MR 16(16%), ORR(50%)(ORR in TD vs. MP p=0.051). Analysis per protocol revealed an ORR of 72% in TD and 52% in the MP group (p<0.01). Time to response and time to best response was significantly shorter in the TD(8, 11 weeks, respectively) compared to MP group (10, 39 weeks, respectively ; p<0.01, p<0.0047, respectively). There were more early treatment discontinuations in the TD arm (20 vs. 8, p<0.007). Patients on MP had statistically more frequently grade III-IV leukopenia, while for thrombocytopenia only a tendency for a higher incidence was noted (14% vs 2% ; p<0.05, and 9% vs. 4%, p=0.252). Patients on TD had more grade II-III neuropathy (28% vs 9%, p<0.001), psyhological toxicity (18% vs. 7%, p<0.02), and a tendency for more skin toxicity (10% vs. 4%, p=0.09) compared to those on MP. Thromboembolic complications were seen in 9% of patients on TD and 4% in those on MP(p=0.15). Summary: TD treatment was associated with significantly shorter time to response and to best response, hogher rate of CR-NCR, and a tendency for higher ORR in the intent to treat analysis. In the per protocol analysis, ORR was significantly higher in the TD arm. Patients on TD had more neuropathy and psyhological toxicity, a tendency for more skin toxicity and thromboembolic complications, and a higher rate of early treatment discontinuations, while hematological toxicity was higher in patients treated with MP. Updated data on time to progression and survival for both groups combined will be presented at the meeting.