Lenalidomide (Revlimid), Bortezomib (Velcade) and Dexamethasone (RVD) for Heavily Pretreated Relapsed or Refractory Multiple Myeloma

We retrospectively reviewed the records of all pts with rel/ref MM who were treated with RVD at Princess Margaret Hospital between March 2009 and March 2010. Eighteen pts were treated with at least 1 full cycle of RVD therapy given as len 10 mg/d on days 1–14, btz 1.0 or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles and dex (20 mg or 40 mg on days of and after btz). Pts routinely received concomitant antithrombotic and antiviral prophylaxis. Primary endpoints were response rate, time to progression (TTP) and toxicity. Responses were assessed according to modified EBMT and Uniform criteria. Toxicity was assessed using NCI-CTC, version 3.0.

Clinical characteristics are seen in Table 1 . Median age was 57 (37-71) years; 55% were female. The median number of prior therapies was 3 (2-6), and the majority of pts had already been treated with len (83%) and btz (78%) separately, and 77% had received both drugs previously but not in combination. In many instances, pts previously treated with len had len added to btz + dex at progression (n=5), or pts previously treated with btz had btz added to len + dex, at progression (n=4). After a median of 4.9 cycles (range 1–14), PR was observed in 7 (39%) and stable disease (SD) in 2 (11%) pts, for an ORR of 39%. Disease progression was seen in 14 pts at a median TTP of 4 months (1-13.6 months). Currently, 6 pts (33%) remain alive at a median F/U of 6.83 months (1.4-18.6 months). Median overall survival was 6.88 months (1-18.6 months) and six patients had a greater than 6 month response. Six pts have experienced grade 3/4 adverse events, including anemia, neutropenia, muscle weakness, hyperglycemia, and pneumonia. No deep vein thrombosis was observed. The side effect profile was manageable; importantly no patient experienced worsening of peripheral neuropathy.

The ORR for our heavily treated patient population was 39% which is lower than that reported by Anderson et al (ASCO, 2009). The median TTP was also short at 4 months. These differences can be partly explained by the fact the majority of our pts had previously received all the agents in RVD, while only 8% of the pts in the Anderson series had prior len exposure. These data suggest that the RVD combination can be effective in rel/ref MM, but responses/duration are affected by very advanced disease stage at relapse and the extent of prior treatment.

Reece:Celgene: Honoraria, Research Funding. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.