June 4, 2012

MMRF Newsflash from ASCO - 3



Welcome to the third and final day of our on-site coverage of ASCO 2012. Highlights today included a clinical sciences symposium discussing immunotherapy for multiple myeloma and a poster session shortly later, covering many myeloma topics.


The oral session included three presentations of monoclonal antibodies for the treatment of myeloma:

·         Dr. Robert Orlowski from the MD Anderson Cancer Center presented results of a Phase II, randomized, double blind, placebo-controlled study comparing the antibody siltuximab, which targets interleukin-6 (IL-6), in combination with Velcade compared to Velcade alone, in 281 patients with relapsed/refractory disease.  Despite promising early data, the experimental arm did not show any benefit in delaying the disease or prolonging survival. Additionally, the experiemtnal arm experienced modestly higher (although generally manageable) adverse events.  However, Dr. Vincent Rajkumar from the Mayo Clinic suggested that perhaps this heavily pre-treated population may have lost sensitivity to IL-6 and that the antibody may still have a role in the upfront or even smoldering setting.  Trials are underway to study the antibody in these contexts.


·         Dr. Torben Plesner from Vejle Hospital in Denmark reported Phase 1 results from a Phase 1/2 study of single-agent therapy with the antibody daratumumab for patients with relapsed/refractory myeloma. To date, 29 patients have been treated at doses from 0.005mg/kg to 16 mg/kg, with a plan to enroll patients in a 24 mg/kg cohort. Infusion-related adverse events were relatively common but were reduced with appropriate pre-medications. In this heavily pre-treated patient population, 7 patients (24%) achieved PR, and an additional 4 patient achieved a minimal response.  The results are extremely early, but worth watching based on these preliminary results.


·         Dr. Philippe Moreau of the Hôpital de Nantes, France, described results of the Phase 2 portion of a Phase 1/2 study of the anti-CS1 antibody elotuzumab, in combination with Revlimid and low-dose dexamethasone in patients with relapsed/refractory myeloma. The Phase 1 portion of this study was recently published in the Journal of Clinical Oncology (June 2012). The Phase 2 study randomized 73 patients to 10 mg/kg or 20 mg/kg elotuzumab plus Revlimid and dexamethasone. The study was generally well-tolerated and showed remarkable efficacy: response rates were 84% overall, 92% in the 10-mg/kg group, and 76% in the 20-mg/kg group; response was higher for patients who had only received one or two prior therapies. Progression-free survival (PFS) at 17 months of follow-up was not reached for the 10-mg/kg group and was estimated at 18.6 months for the 20-mg/kg group; PFS was significantly lower for patients with higher-risk cytogenetics (about 9 months). Two Phase 3 studies are currently underway using the 10-mg/kg dose, comparing this combination with Revlimid + low-dose dexamethasone in the upfront (ELOQUENT 1) and relapsed/refractory (ELOQUENT 2) setting.


A poster session following these oral presentations included new data for carfilzomib, analyses of potential prognostic risk factors, and various subgroup, follow-up, or retrospective analyses.


Dr. James Berenson of the Institute for Myeloma and Bone Cancer Research presented results of an interesting Phase I/II study of carfilzomib for 27 patients who progressed on or within 12 weeks of receiving a Velcade-containing combination regimen. These patients received the same treatment regimen upon progression but with carfilzomib as a replacement for Velcade. 14 of 22 evaluable patients (64%) subsequently achieved at least a minimal response, and 11 patients (50%) achieved at least a very good partial response. Additionally, in a pooled analysis of 4 Phase 2 studies of carfilzomib in relapsed/refractory myeloma, Grade 3/4 hematologic AEs were infrequent and transient, and serious events were rare.


Several posters described retrospective analyses (using existing medical records) of the effect of early stem-cell transplants (as consolidation therapy after induction):

·         A poster with Jonathan Kaufman from Emory University demonstrated that achieving at least a VGPR following stem cell transplant and then RVD maintenance resulted in significantly improved progression free and overall survival.

·         A related poster by Charise Gleason from Emory University demonstrated the ability of RVD induction, consolidation stem cell transplant, and then maintenance to improve progression-free and overall survival.

·         Fnally, the value of a second stem cell transplant as salvage therapy was demonstrated by Dr. Wilson Gonsalves from Rochester, noting that time to progression for the first transplant was associated with higher progression-free and overall survival following a second transplant.


We hope you found these updates useful!