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This afternoon's oral sessions on myeloma featured four much-anticipated studies: Antonio Palumbo's (University of Torino, Italy) report on his VMPT-VT vs. VMP trial for 511 newly diagnosed patients ineligible for transplant (abstract 22); Martha Lacy's (Mayo Clinic, Rochester, MN) summary of data from 6 phase II trials at Mayo with pomalidomide and dexamethasone for 345 patients with relapsed/refractory myeloma (abstract 201); Paul Richardson's (Dana-Farber Cancer Institute, Boston, MA) report on the phase II study of the monoclonal antibody elotuzumab + len/dex for relapsed/refractory disease; and Michael Savona's (Sarah Canon Research Institute, Nashville, TN) presentation of the phase Ib dose-escalation study of oprozomib (Onyx's oral proteasome inhibitor). 

The four-drug regimen of VMPT-VT, which is VMPT Velcade, melphalan, prednisone, and thalidomide with two years of maintenance with Velcade and thalidomide, out-performed triplet VMP with no maintenance, the current standard of care in Europe, both in PFS and OS. Dr. Palumbo demonstrated that the 4-drug regimen with continuous therapy provided better disease control.  Due to toxicities in the elderly (>75 years) patients, however, it is a better regimen for those age 65-75.

Dr Lacy's presentation, a model of clarity and fluency, covered data on pom/dex studies performed at Mayo between 2007 and 2012.  Although dosing and eligibility criteria varied among the studies, the patients were heavily pretreated, 40% had abnormal cytogenetics, 17% had 17p deletion, and 44% were high risk.  Even in this population, the overall response rate of PR or better was 35%.   When asked, Dr. Lacy explained that the key differences between lenalidomide and pomalidomide are 1) pomalidomide can work in patients who are refractory to lenalidomide; 2) there is much less myelosuppression (impairment of the bone marrow's ability to make new blood cells) with pomalidomide than with lenalidomide, and 3) pomalidomide does not cause skin rash, as lenalidomide sometimes does.

Dr. Richardson's review of the data from the phase II study of elotuzumab +len/dex was also extremely encouraging.  In this study, a 10 mg/kg intravenous dose of the monoclonal antibody was compared with a 20 mg/kg dose.  We were all surprised to learn that the overall response rate in the 10 mg/kg group was 92% in this relapsed and refractory population, while the response rate in the patients treated with 20 mg/kg was 76%.  Sometimes, less really is more!  Responses were very rapid with either dose: one month for response and two months for best response.  PFS has not yet been reached in the 10 mg/kg group. We expect to see more of this drug in various combination studies that are ongoing.

We ended our day at the foreign journalists' workshop, where we were moved by the stories of four patients who have surmounted many obstacles with a combination of good therapy, good luck, and personal pluck. They are a testament to the will to live well and fully and to the effectiveness of novel therapies. The workshop also featured updates on research that has been or will be presented at the ASH meeting highlighted by Drs. Brian Durie, Paul Richardson, Robert Orlowski, and Xavier Leleu, followed by questions from foreign journalists.  There was also an impassioned plea to the press from Brazilian myeloma specialist Dr. Vania Hungria to advocate for the approval of Revlimid in Brazil.  Those of us who live in countries where we have access to the latest treatments must never take that access for granted.  It is heartbreaking that effective new therapies continue to be developed but are not available to patients in many parts of the world.  


After two days of anticipation, the first oral session in myeloma was at last presented starting at noon today. This session dealt with phase I/II studies of drugs for relapsed and refractory myeloma, including a single-agent study of an anti-CD 38 monoclonal antibody, daratumumab; the combination of carfilzomib with pomalidomide and dex; the first-time combination of dexamethasone with two immuno-modulatory agents, lenalidomide (Revlimid) and thalidomide; a single-agent study with a novel CDK inhibitor, dinaciclb; the combination of clarithromycin with pomalidomide and dex (nicknamed clap-d); and the first-ever drug developed in China, circular permuted TRAIL (CPT).

The daratumumab study presented by Dr. Torben Plesner from Vejle, Denmark, was noteworthy because this monoclonal antibody demonstrated responses in myeloma patients as a single agent in an early-phase trial. 15 out of 32 patients enrolled had reductions in their monoclonal protein, and there were 4 partial responses. It and elotuzumab are the two monoclonal antibodies that researchers are really keeping their eyes on.

Another highlight of the session was Jatin Shah's (MD Anderson, Houston, TX) presentation on the combination of carfilzomib, pomalidomide, and dex. The patients were heavily pre-treated, and 10 of the 46 were refractory to lenalidomide. The overall response rate was greater than 50%, with 13% complete or near-complete responses.

Dr. Shah's second presentation on the surprising combination of lenalidomide, thalidomide, and dex demonstrated that one IMiD can be used to overcome resistance to another. The overall response rate was 51%.

Dr. Tomer Mark's (NY Presbyterian/Cornell-Weill Medical Center, NY) study of clap-d provoked some skepticism with its dramatic improvement in progression-free and overall survival in patients who had received clap-d over patients treated with pomalidomide and dex alone. The addition of clarithromycin, an antibiotic, in a population of patients who had received between 5 and 15 prior lines of therapy, produced an overall response rate of 57%, with 6% stringent complete responses. 75% of the patients were refractory to both IMiDs and proteasome inhibitors. Dr. Jesus San Miguel asked Dr. Mark why he didn't do a clinical trial comparing therapies with and without clarithromycin, and Dr. Mark responded that it was not possible to get funding for such a study. Although the data was clear, there remain unbelievers.

Later today there will be a second oral session for myeloma. Stay tuned for blog updates, and look for the complete highlights publication with more studies and more details after the meeting is concluded.

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