Thalidomide-Dexamethasone Induction Followed by Autologous Transplantation in Young Patients with Multiple Myeloma

Research Article

Ann Hematol Oncol. 2016; 3(3): 1081.

Thalidomide-Dexamethasone Induction Followed by Autologous Transplantation in Young Patients with Multiple Myeloma

Kmira Z¹*, Ikbel BH¹, Houneida Z², Monia Z¹, Hela Z³, Yosra BY³ and Abderrahim K¹

¹Department of Clinical Hematology, Farhat Hached University Hospital, Tunisia

²Department of Radiology, Farhat Hached University Hospital, Tunisia

³Department of Rheumatology, Farhat Hached University Hospital, Tunisia

*Corresponding author: Zahra Kmira, Department of Clinical Hematology, Farhat Hached University Hospital, Sousse, Avenue Ibn Eljazzar Sousse 4000, Tunisia

Received: April 04, 2016; Accepted: May 31, 2016; Published: June 02, 2016


Aim: Thalidomide plus dexamethasone (TD) has shown encouraging results in newly diagnosed multiple myeloma (MM) in small, uncontrolled trials. The aim of the present retrospective study was to compare the efficacy and toxicity of TD and melphalan and prednisone (MP) in young MM patients.

Methods: In this retrospective study, patients with symptomatic MM were treated with TD (arm A) or MP (arm B). Patients in arm A received oral thalidomide 200 mg daily associated to oral dexamethasone 20 mg/m² on days 1-4, 9-12, and 17-20 of the first and the third cycle and on days 1-4 of the second cycle (28-day cycles). Patients in arm B received six 30-day cycles of melphalan at the dose of 0.25 mg/kg/day on days 1-7 of each cycle associated to prednisone at the dose of 2 mg /kg/day on days 1-7 of each cycle. Thirteen patients in the arm A received high dose therapy (HDT) with autologous stem cell transplantation (ASCT).

Results: Thirty six patients were enrolled: 24 patients in the arm A and 12 patients in the arm B. The response rate with TD was significantly higher than with MP (77.3% versus 50%, respectively). The overall survival (OS) and the event free survival (EFS) at 18 months were higher in TD versus MP (76% v 37%; p= 0.028 and 63% v 33%; p= 0.019, respectively). The OS and the EFS at 18 months were higher in the arm autograft versus the arm no-autograft (90% versus 44.7%; p= 0.004 and 61.7% versus 40%; p =0.01, respectively). No statistically significant difference was observed between arms TD and MP in terms of neutropenia, anemia, thrombocytopenia, deep vein thrombosis and peripheral neuropathy (P >0.05).

Conclusion: TD demonstrates significantly superior response rates in newly diagnosed myeloma compared with MP. ASCT improves outcome in young MM patients.

Keywords: Multiple myeloma; Melphalan; Prednisone; Thalidomide; Dexamethasone


Multiple myeloma (MM) is a malignant plasma-cell proliferative disorder that accounts for approximately 10% of hematologic malignancies [1]. For many years, melphalan plus prednisone (MP) had remained the standard therapy for this disease. Response rates with this therapy are approximately 50%; median survival is approximately 3 years [2-3]. First-line treatment in MM aims primarily at high response rates and early reduction of tumor burden, achieved with least possible toxicity to bone marrow stem cells, since high dose therapy (HDT) with autologous stem-cell transplantation (ASCT) in eligible patients is by now the only therapeutic strategy that prolongs OS [4-6]. So, vincristine, doxorubicin, and dexamethasone (VAD) and VAD-like regimens including vincristine, liposomal doxorubicin and dexamethasone (VAD-doxil), have replaced MP and been widely accepted as first-line treatment in MM during the last two decades, including early, objective responses in 55-67% of patients [7]. Thalidomide was firstly explored for the treatment of advanced and refractory MM by Singhal et al. in 1999 with a response rate of 25% to 35% [8]. The rationale for using this drug in patients with progressive MM relied upon the notion that increased bone marrow angiogenesis correlates with advanced phases of MM [9] and on data from previous studies showing the antiangiogenic activity of thalidomide in vitro [10]. In combination with dexamethasone, response rates increase to approximately 50% in relapsed refractory disease [11]. Three phase II trials have been conducted with the thalidomide plus dexamethasone (TD) combination in newly diagnosed MM. In the Mayo Clinic trial, 50 patients were treated and 64% responded to therapy [12]. Similar response rates were seen in the M.D. Anderson clinical trial and the Italian clinical trial, respectively [13,14]. As a result of these phase II trials, the use of TD has increased significantly in standard practice. Some studies have reported the superiority of TD compared with VAD based on short-term response rates [15,16].

The goal of this study was to compare the response rate, the overall survival (OS), and event free survival (EFS) of TD followed by ASCT versus MP in young patients (< 65 years) with newly diagnosed MM.

Materials and Methods


It is a retrospective study including 36 patients with newly diagnosed MM treated in Clinical Hematology department from March 2007 to December 2011. Patients 18 to 65 years of age with secretory and non-secretory MM Durie-Salmon stage II to III were eligible (Table 1). Exclusion criteria were asymptomatic stage I, systemic amyloid light chain amyloidosis, neuropathy grade ≥ 2, active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma, HIV positivity, serum bilirubin ≥ 30 μmol/L or aminotransferases ≥ 2.5 x normal level, pregnancy and severe psychosis. Patients with renal impairment were not excluded.