December 10, 2012

MMRF Newsflash from ASH 2012 - Volume 3

Welcome to our third day of onsite coverage from the 2012 American Society of Hematology (ASH) Annual meeting. Oral sessions today covered new therapies for patients with newly diagnosed multiple myeloma, as well as for those with relapsed/refractory myeloma. The day concluded with more presentations and posters some featuring compounds in very early development for myeloma.

Upfront Therapy

Dr. Shaji Kumar from the Mayo Clinic-Rochester presented data from a phase I/II trial on the ixazomib, (MLN9708) a new oral proteasome inhibitor from Millennium, combined with Revlimid (lenalidomide) and dexamethasone in previously untreated myeloma patients. The overall response rate in this trial was 100%, with 23% complete responses (CR). Importantly, the incidence of peripheral neuropathy was very low, with only one grade 3 occurrence. The most common side effects were fatigue, nausea and vomiting. Based on the positive results, a phase III trial is planned.

Dr. Jonathan Kaufman (Atlanta, GA, USA) presented results from a phase I study of Revlimid, Velcade (bortezomib), and dexamethasone combined with the histone deacetylase (HDAC) inhibitor Zolinza (vorinostat) as first-line therapy. Commonly seen toxicities included Grade 1 or 2 constipation, diarrhea, fatigue, and nausea. The overall response rate was 97%, including a very exciting number of very good partial responses (VGPR) and complete or near complete responses (CR). Although Zolinza does not have an FDA-approved indication for multiple myeloma, it is approved for a type of lymphoma.

Relapsed/Refractory Disease

Dr. Antonio Palumbo from the University of Torino, Italy, presented results on a trial evaluating pomalidomide, cyclophosphamide, and prednisone in relapsed/refractory patients followed by pomalidomide and dexamethasone maintenance therapy. This trial is ongoing. At the time of this presentation, 55 patients had received at least 1 treatment cycle. Patients with relapsed/refractory disease who had received at least 1 to 3 prior therapies were eligible to participate. The overall response rate was 51%, with 6% achieving a CR and 24% a VGPR.

Dr. Noopur Raje from Mass General presented data for a phase I trial of the new anti-BAFF antibody tabalumab, combined with Velcade and dexamethasone. Forty-eight patients were enrolled, who had a median of 3 prior treatments. Adverse events observed were similar to those seen with Velcade. Two patients had a CR, 20 had a PR or VGPR, 21 had stable disease, and 3 progressed. The phase II trial is ongoing. The MMRF funded some of Dr. Raje’s early preclinical research on this target.

Dr. Jatin Shah from MD Anderson presented the results of a phase II trial assessing ARRY-520, a novel KSP inhibitor, with or without dexamethasone. Patients were heavily pre-treated, with a median of 6 prior treatments. Grade 3 and 4 toxicities were low, there was no cumulative toxicity, and the treatment was well tolerated. Responses ranged from PR to SD, with no CR in these heavily treated patients, and 34% had progressive disease. Interestingly, responses to this agent corresponded to serum levels of alpha-1-acid glycoprotein, which can act as a marker for patients who may respond to this agent.

Dr. Sundar Jagannath from Mt Sinai in New York City presented results of an age analysis from the phase II trial of pomalidomide with low-dose dexamethasone (in which the MMRC participated) in patients with relapsed/refractory multiple myeloma who have received prior therapy with Revlimid and Velcade. The results showed no significant differences in responses between the groups.

CoMMpassSM Study

At tonight’s poster session, our own Chief Medical Officer Dr. Michael Needle presented data from the MMRF’s CoMMpass Study, for which he is co-principal investigator. The CoMMpass study will analyze the tumor and normal genomes from 1,000 patients with newly-diagnosed active multiple myeloma from their initial diagnosis over an at least five years. The clinical study opened in July 2011 and includes 55 sites in the United States. CoMMpass will provide researchers insight into patients’ disease progression and their responsiveness to specific treatment regimens, thereby characterizing the subtypes of multiple myeloma and accelerating individualized treatment approaches, which will be so important in this heterogeneous disease.

As mentioned, there were many new compounds representing many different classes in early development for myeloma presented at this year’s ASH meeting. Excitingly, there are too many to discuss on this blog, but I recommend that you check out the MMRF’s webcast with Dr. Antonio Palumbo and Professor Gareth Morgan.