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MMRF BLOG


 December 9, 2012

MMRF Newsflash from ASH 2012 - Volume 2

Greetings!

Welcome to our second day of on-site coverage of the 2012 American Society of Hematology (ASH) Annual meeting. Today there were several exciting oral and poster sessions specifically focusing on new treatments for multiple myeloma.

Monoclonal antibodies

Dr. Paul Richardson from Dana-Farber presented an update on a phase II study of the monoclonal antibody elotuzumab (which targets CS1) given at 2 different doses (10 mg/kg or 20 mg/kg) combined with Revlimid and low-dose dex to treat patients with relapsed/refractory multiple myeloma who had not received Revlimid. The overall response rate of patients was 84% with slightly higher responses seen at the lower dose. As we saw with pomalidomide, the response rate is higher in those patients who have had fewer prior treatments, which means that understanding sequencing of treatments is critical. Patients with high-risk disease did not differ in their responses but had a significantly lower progression free survival, again underscoring the need to understand which patients will benefit most from which treatments. The most common side effects that patients experienced were similar to those seen with Revlimid treatment. This treatment is in phase III trials in both relapsed and newly diagnosed patients.

Dr. Torben Plesner from Denmark presented the results of a phase I study of the new monoclonal antibody, daratumumab, which targets CD38. Patients with advanced disease who had received several previous treatments including immunomodulatory agents (IMiDs), proteasome inhibitors, and stem cell transplantation were enrolled in the trial and received single-agent daratumumab. There were several responses and importantly, there were minimal side effects. Although the results are preliminary, they are promising. Sanofi also has an antibody against the same target in a phase I trial at UCSF.

Pomalidomide

Dr. Jatin Shah from MD Anderson presented results from a phase 1 study looking at two of the newest agents in combination - Kyprolis (carfilzomib) plus pomalidomide and dexamethasone – in a highly refractory population. All patients (n=32) were refractory to Revlimid, and 31/32 were refractory to Velcade. Side effects were manageable, primarily low blood caounts, and notably, no grade 3 or 4 periperal neuropathy was seen. The overall response rate was 50 and nearly every patient had a minor response or stable disease. And, importantly, though the numbers of patients were small, even those patient who were high-risk (eg, with a deletion of chromosome 17p) responded as well as those patients who were not high-risk. Progression-free survival was 7.4 months, and the 1-year overall survival was 90%. These data continue to show that there are new treatments that can work even in the most heavily refractory and pre-treated population.

Dr. Tomer Mark from Weill-Cornell presented results from nearly 100 patients treated with clarithromycin (Biaxin) plus pomalidomide-dex again in a heavily pre-treated and refractory population. The overall response rate was 57% with a median progression free survival of 8.67 months. There was no difference in responses or progression-free survival between low and high-risk patients. The study is also looking at overall survival, and median survival had not yet been reached. Interestingly, during the Q&A, Dr. Mark mentioned that there are much more pronounced responses with this combination as opposed to the earlier clarithromycin plus Rev-dex trial. The study is continuing to enroll patients.

Dr. Martha Lacy from the Mayo Clinic presented updated results on a number of small trials conducted there with pomalidomide, and her data supported what was seen in Dr. Shah’s and Dr. Mark’s data – that pomalidomide can work even in those heavily pretreated and refractory patients – though, not surprisingly, the higher responses were seen in patients who had had fewer prior treatments. Regardless of dose or population, side effects were again quite manageable, which again is promising in this population.

Two more days to go. Stay tuned!