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.