Lenalidomide Plus Low-Dose Dexamethasone Compared with Thalidomide Plus Low-Dose Dexamethasone: A Randomised Phase III Study
Authors: Mookerjee Anjali , Gupta Ritu , Sharma Atul , Saikia Tapan , Kumar Lalit 
Published: October 2019

Abstract
Abstract 2932

Background:
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.

Methods:
Between 1st March 2009 and 30th 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.

Results:
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.

Conclusion:
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.

Disclosures:
No relevant conflicts of interest to declare.