June 3, 2014

MMRF Newsflash from ASCO 2014 - Volume 3

Welcome to our third and final report on the 2014 American Society of Clinical Oncology Annual meeting featuring the Multiple Myeloma poster session.

Posters featured ongoing trials in newly diagnosed and relapsed/refractory patients, updates and potential new ways to use Pomalyst and Kyprolis, as well as early studies of new drugs.

Ongoing trials in newly diagnosed high risk patients

  • A Phase II study is ongoing in newly diagnosed patients with high risk (aggressive) myeloma. This study will evaluate whether adding elotuzumab, a new monoclonal antibody in late-stage clinical development, to Revlimid-Velcade-dex is beneficial.
  • An ongoing Phase III trial is evaluating this combination.

Updated data and ongoing trials in relapsed/refractory patients

Several posters focused on the use of Pomalyst-low-dose dexamethasone and one study highlighted a new combination treatment with this drug.

  • Previously, a large Phase III study showed that Pomalyst plus low-dose-dex extended survival and time to disease progression in relapsed/refractory patients vs dexamethasone alone. An updated analysis indicated that the advantage of Pomalyst plus low-dose dex as compared to high-dose dex may be even greater than previously reported.
  • Additional studies are underway to learn more about the use of Pomalyst.
    • A large study is underway to look at the role of Pomalyst based on the genetics of patients’ myeloma. Data presented at last year’s American Society of Hematology (ASH) meeting indicated that Pomalyst may be effective in patients with genetic mutations like del17(p), whose disease is typically harder to control.
    • Two Phase II trials are underway to learn more about the use of Pomalyst-low-dose dex in different patient types including patients who have recently progressed on Revlimid-based therapy and those with moderate or severe kidney problems. Early results look promising, confirming that Pomalyst works effectively in many patients with difficult to treat myeloma.
  • The combination of Pomalyst and Velcade-dex was evaluated in an early study. Preliminary data showed that this combination was highly effective in patients who were both refractory to Revlimid and had previously received Velcade. 70% of patients responded and on average the responses lasted for 7.4 months. A Phase III trial evaluating this combination is underway.

In addition, one small study is looking at the combination of Kyprolis and dexamethasone. Preliminary data showed that 63% of patients responded and the combination was well tolerated.

Early studies with novel agents in relapsed/refractory patients

  • Among the new drugs being studied in early trials in combination with Revlimid are MK-3475 and romidepsin. MK-3475 is monoclonal antibody (part of a class called checkpoint inhibitors that are showing tremendous promise in some solid tumors like melanoma and lung cancer) that works to utilize the immune system to kill cancer cells. Romidepsin is a HDAC inhibitor (like panobinostat) but is already FDA approved for a type of lymphoma.
  • A laboratory study demonstrated that marizomib, an oral proteasome inhibitor in development, may work well in combination with Pomalyst. This combination is currently being studied in a trial sponsored by the Multiple Myeloma Research Consortium (MMRC), an affiliate organization of the MMRF.

Other Studies

  • One study looked at ways to identify which patients with smoldering myeloma are at higher risk of progression to symptomatic myeloma. In this study, patients with higher levels of free light chains (a portion of an antibody) and certain types of DNA abnormalities were more likely to progress to symptomatic myeloma.
  • Another study evaluated the different tests used to assess bone in patients with MGUS, smoldering and active myeloma. Like other studies, this one confirms that newer imaging techniques such as MRI and CT-Scan can be more effective in detecting disease progression than whole body scans (standard x-rays).