December 7, 2013

MMRF Newsflash from ASH 2013 - Volume 1

Welcome to our first report on the 2013 American Society of Hematology (ASH) Annual meeting, featuring many posters on multiple myeloma.

Tonight, the poster session focused on new agents being tested in patients with relapsed and refractory disease. These included new doses/schedules and combinations of the most recently FDA approved agents, ie, Kyprolis (carfilzomib) and Pomalyst (pomalidomide) as well as novel agents in early phase clinical trials.

Highlights included:

  • Results from a Phase I/II study of the combination of Kyprolis plus panobinostat (an HDAC inhibitor with recently announced positive Phase III data) presented by Dr. Berdeja from Sarah Cannon Research Institute and a member of the Multiple Myeloma Research Consortium (MMRC). Overall, 66 patients were treated, many of whom were refractory to IMiDs, proteasome inhibitors or both. The overall response rate was 64% when all patients were considered, and 67% in PI refractory patients. The median time to progression in the overall and PI refractory populations was 7.56 and 4.83 months, respectively. Thrombocytopenia (low platelets) was the only serious (Grade 3 or 4) side effect seen with any frequency.
  • Very preliminary results (on a total of 11 patients) looking at the combination of the antiCD38 antibody daratumumab in combination with Revlimid and dexamethasone (Rev-dex) were presented. To date, 8/11 in this dose-finding study had a partial responses (PR) or better, 10/11 were receiving clinical benefit (minor responses and better), and the side effects seen were predominantly consistent with those seen with Rev-dex. Though very early, the early signal is very promising.
  • Dr. Jim Berenson of the Institute for Myeloma & Bone Cancer Research presented the results of a Phase I study (CHAMPION-1) investigating once weekly Kyprolis combined with dexamethasone. Kyprolis was given as a 30-minute infusion at three different doses. Results were available for 27 patients. Eight patients (30%) achieved a complete response (CR) and the overall response rate was 63%. Side effects were predominantly myelosuppression (low blood counts) and gastrointestinal (GI) related.
  • Dr. Chari from Mount Sinai in New York presented the results of a Phase I study of a new KSP inhibitor – ARRY-520 combined with Velcade and dexamethasone. All patients in the trial had previously received a proteasome inhibitor. The ORR was 42%, and it was 30% in the PI refractory patients. Toxicities were generally mild and largely GI-related or low blood counts. Another poster examined the compound with Kyprolis with similarly promising results in a refractory population.
  • Dr. Mikhael of the Mayo Clinic Arizona in Scottsdale presented the results of a Phase I/II trial of Pomalyst, Velcade, and dexamethasone in 16 patients in the phase II part of the trial. All patients had been treated previously with Revlimid. Though only a few patients were treated, the ORR was an impressive 94%. The most common drug-related toxicities were anemia, fatigue, leukopenia and thrombocytopenia; however, the majority of these were grade 1-2.

Other novel compounds presented included quisinostat, a novel HDAC inhibitor and veliparib, a PARP inhibitor, both of which show some promise in very early trials.

Finally, in addition to the clinical posters, several others looked at evaluating minimal residual disease through more sensitive DNA sequencing techniques, as well as markers to determine how well patients will do with treatment. These studies included a study done in collaboration with the MMRC reporting on the use of SKY92, a genetic marker of high risk multiple myeloma. These studies will help with diagnosis and treatment decisions, and help evaluate the responses to treatment for myeloma patients.

To see the full MMRF coverage from ASH with ongoing updates, please visit: www.themmrf.org/ash2013.