Pulsed Cyclophoshamide, Thalidomide and Dexamethasone (CTD) Regimen for Previously Treated Patients with Multiple Myeloma: Long Term Follow up and Disease Control after Subsequent Treatments.

Abstract Introduction: The effectiveness of thalidomide based regimens in patients with relapsed/refractory multiple myeloma is well established. However, there is still limited data regarding the long term follow up after such regimens and the outcome of patients when they progress and they receive further treatment. In order to answer these questions we reassessed our original series of 43 patients with previously treated multiple myeloma who were treated with a pulsed, oral CTD regimen between December 2000 and April 2002 (Dimopoulos MA, Hematol J2004;5:112). The CTD regimen consisted of oral cyclophosphamide 150 mg/m2 every 12 hours before meals on days 1 to 5, thalidomide 400 mg p.o. in the evening on days 1 to 5 and 14 to 18 and dexamethasone 20 mg/m2 in the morning after breakfast on days 1 to 5 and 14 to 18. The CTD combination was repeated every 28 days for three courses. Subsequently, responding patients were scheduled to receive maintenance treatment with monthly courses of CTD administered only for the first five days of each month. Patients and Methods: Progression free survival after initiation of CTD was updated in June 2006,ie more than 4 years after inclusion of the last patient. Type of treatment at the time of progression after CTD, response to this treatment and progression free survival were recorded for each patient. Results: Among the 43 patients, 14 had not responded to CTD and 29 (67%) had achieved at least a partial response. The median PFS for all patients was 10 months. As of June 2006, 3 patients remain off treatment and without progression for 55+, 55+ and 56+ months respectively. Thus, 40 patients were analyzed for further treatment and outcome. Ten patients (25%) died before receiving further treatment, 9 patients(23%) received conventional chemotherapy and 21 patients (52%) received continuous thalidomide and dexamethasone(15 patients), melphalan-bortezomib-dexamethasone and intermittent thalidomide (3 patients) or lenalidomide with dexamethasone (3patients). Among the 21 latter patients,6(28%)achieved at least partial response. A response was documented in 31% of CTD-sensitive patients (ie patients who had responded to CTD and then progressed) and in 20% of CTD-resistant patients (ie patients who had not responded to CTD). The median progression free survival of the 21 patients who received retreatment with novel agents plus dexamethosone was 5,3 months and the median survival was 10 months. Among the 9 patients who received conventional chemotherapy only one patient responded and the progression free survival was 2,8 months. Conclusions: After an oral pulsed CTD regimen 7% of patients remain without treatment and free of progression for more than 4 years. Further control of myeloma was achieved in one-third of patients who progressed after CTD and who received further treatment which included a novel agent.