Thalidomide, Dexamethasone and Pegylated-Liposomal Doxorubicin (ThaDD) for Untreated Multiple Myeloma Patients Aged over 65 Years.

No standard therapy is still available for older patients with multiple myeloma (MM) despite two third of patients aged over 65 years.The combination melphalan-prednisone yields unsatisfactory results and high-dose therapy can be too toxic or unfeasible.Thalidomide has opened up new horizons also for the treatment of older patients with MM.This multicenter study included patients with de novo symptomatic MM older than 65 years regardless of comorbidities, performance status and renal function. All patients received thalidomide 100 mg continuously, pegylated-liposomal doxorubicin (Caelyx®) 40 mg/m² on day 1 every 28 days, dexamethasone 40 mg on days 1–4 and 9–12.They also were given warfarin 1.25 mg/day for prophylaxis of thromboembolic disease and ciprofloxacin 250 mg twice daily after a high incidence of infections was recognized. Forty-one patients are valuable for response and toxicity so far.Median age was 72 years (range 64–78) and 63% were older than 70 years. Baseline characteristics are the following: clinical stage III in 30 patients (70%), PS>2 in 7(18%), ISS≥2 in 73%, creatinine≥2 mg/dl in 15%, unfavourable cytogenetics in 33% of patients with a valuable test. Fifteen patients (37%) achieved CR according to the EBMT criteria, 4 (10%) nCR, 4(10%) VGPR, 15(32%) PR, 4(10%) MR and one patient progressed resulting an ORR of 98%.The majority of the best responses were achieved within the first 3 cycles of therapy. Eight patients underwent autologous stem cell transplantation.Side effects were mild or moderate according to NCI scale.Severe non-hematological toxicity consisted of constipation (7%), fatigue (5%), tremors (2%), mucositis (4%).No patients had peripheral neuropathy or PPE more than grade 2. Grade 3–4 neutropenia was seen in 4(10%) of patients but severe infections occurred in 7(17%) without related deaths. DVT occurred in 5 patients (12%) with one case of pulmonary embolism; all cases resolved with common anticoagulant therapies.No patients discontinued the protocol because of toxicity although two patients refused to continue it after the occurrence of pulmonary embolism and septic shock.With a median follow-up of 15 months, EFS and OS at two years were 65% and 70%, respectively.Our study demonstrated that low-dose thalidomide in combination with pegylated-liposomal doxorubicin and high-dose dexamethasone is very effective inducing an ORR and particularly a CR rate higher than those reported with all other treatments, including high-dose therapy.High quality of response positively impacts on EFS and OS. This combination results well tolerated also by older-frail patients but infections and thromboembolic disease require adequate prophylaxis and therapy. An update of these data will be presented.