Lenalidomide Plus Low-Dose Dexamethasone Compared with Thalidomide Plus Low-Dose Dexamethasone: A Randomised Phase III Study

We prospectively studied the efficacy and safety of Lenalidomide and Thalidomide in conjugation with low-dose dexamethasone in previously untreated symptomatic multiple myeloma (MM) patients. The results from an interim analysis of this on-going trial are presented.

Between 1^st March 2009 and 30^th June 2011, 56 patients with previously untreated symptomatic MM were enrolled to receive 4 cycles of either Lenalidomide 25 mg daily from day 1 to 21 of a 28-day cycle (Arm A) or Thalidomide 100 to 200 mg daily (Arm B). Patients in both arms received dexamethasone 20 mg from day 1 to 4 and 9 to 12 along with monthly zoledronic acid. EORTC quality of life questionnaire C-30 version 3.0 was answered by all the patients at the start of treatment and at the end of 4 cycles. Data from 38 patients who have completed 4 cycles treatment is being analysed. Responses were assessed by International Myeloma Working Group (IMWG) criteria. Adverse events were graded according to CTCAE version 3.0.

Patients' characteristics are similar in both arms with respect to age, sex, stage and myeloma subtype. Median age (range) of patients is 54 yr (40 to 65) in arm A and 48 yr (37 to 65) in arm B. Gender: male/female 12/7 in arm A and 13/6 in arm B. ISS stage: I/II/III - 5/7/7 and 9/4/6. with Durie-Salmon stage: IIA/IIIA/IIIB - 1/14/4 and 2/13/4. Myeloma subtype included IgG/IgA/light chain: 11/2/6 and 14/3/2 in arms A and B, respectively.

Currently 38 patients are evaluable for response (19 in each arm), 17 and 19 patients responded (PR or higher) in arms A (74%) and B (84%) respectively. Arm A: sCR-1, VGPR-5, PR-8, stable (SD)-3, progressive disease-2. Arm B: VGPR-5, PR-11 and SD-3 (p=0.46). Two patients have been lost to follow up in both arms. Two and 1 patients died of progressive disease in arms A and B respectively. The median time to response was 4 weeks in arm A compared with 11 weeks in arm B (p<0.002).

Ten patients have undergone autologous stem cell transplantation and are currently on maintenance therapy.

Grade 3 / 4 toxicities in Len/dex arm included: neutropenia-2 (10.5%), thrombocytopenia-2 (10.5%) and anemia in 2 (10.5%) patients. Other common adverse reactions included URTI, dryness of mouth and dysguesia. One patient developed autoimmune thrombocytopenia.

Patients in the Thal/dex group had constipation, grade 3 in 1 (5%) patient, tremors-2 (10.5%) and grade 1 sensory neuropathy occurred in 9 (47%) patients.

Analysis of quality of life data revealed significant improvement in all the scores in both arms after 4 cycles compared to baseline. Improvement in global QOL score was similar in both arms (p=0.37). Median baseline global QOL score was 25 (range, 0–66.67) and 33.33 (range, 16.67–50) in arms A and B, respectively. Post 4 cycles, median global QOL score was 50 (range, 0–83.33) and 50 (range, 33.33 to 100) in arms A and B, respectively.

Patients in Lenalidomide and low-dose dexamethasone had a more rapid response than those treated with Thalidomide and low-dose dexamethasone. Myelosuppression was the major toxicity in Len/dex arm while sensory neuropathy was the prominent adverse effect noted with Thalidomide.

No relevant conflicts of interest to declare.