May 6, 2011

Updates from Day 3 at IMW, Sandra Wear

Day 3 of IMW began with an overview of treatments for newly diagnosed patients aged 65 and older. Several trials were presented, each with a slightly different approach to providing patients in this population with the best treatment while limiting toxicities. Overall, with the integration of newer agents like Velcade and Revlimid, we are now starting to see responses resembling those seen in younger patients who can tolerate tougher treatments - high dose chemo and transplants.

Additionally, several updates were provided regarding drug classes currently used to treat MM, specifically proteasome inhibitors and IMiDs. Data on carfilzomib, a second generation proteasome inhibitor which has been studied in four MMRC- facilitated clinical trials, continued to show very low incidence of PN (peripheral neuropathy) and responses in patients that have relapsed or are refractory to Velcade and/or Revlimid. Additionally, use of subcutaneous Velcade has been shown to reduce PN by approximately 50% while new oral formulations of proteosome inhibitors are currently in clinical trials which should provide a much easier route of administration when compared to intravenous delivery, including Millennium’s MLN9708. Pomalidomide, a more potent IMID, was also highlighted for its ability to overcome resistance to Velcade and Revlimid, as shown in trials facilitated by the MMRC and the Mayo Clinic.

Newer classes of drugs such as histone deacetylace inhibitors (HDAC) were highlighted for their ability to amplify Velcade’s activity and in some cases, overcome Velcade resistance. The MMRC participated in a key Phase 2 trial combining Zolinza, another HDAC inhibitor, and Velcade, as well as early trials of panobinostat, both of which are in Phase 3 clinical trials.

Monoclonal antibody therapy was also discussed. In particular, elotuzumab, which is entering a Phase 3 clinical trial in combination with Revlimid and dexamethasone, was also studied within the MMRC. This compound also helped amplify the effectiveness of Revlimid in the relapsed/refractory patient population. Other exciting monocolonal antibodies in earlier development include those targeting IL-6 and anti-CD38.

Perhaps the most highly anticipated session focused on the use of Revlimid maintenance. Encouragingly, for the first time, data from the US CALGB study showed an overall survival benefit. Grade 3 toxicities were reported for the Revlimid maintenance arm and were manageable. There continued to be an increase in the incidence of secondary malignancies in the Revlimid arm; however, given the survival benefit, the researchers presenting during this session agreed that, particularly for patients who did not achieve at least a very good partial response following high-dose chemotherapy and stem cell transplant, based on currently available data, the benefits do appear to outweigh the risks. It will be critical, however, to continue to follow these patients as well as those participating in other trials that combined Revlimid with melphalan to better understand the benefits and risks over time.