ASCO 2011 Multiple Myeloma Update – Day Four

Monday was the fourth day of the American Society of Clinical Oncology (ASCO 2011) annual meeting in Chicago. Although the meeting concluded yesterday, Monday was the last day of the meeting that contained any myeloma-relevant material.
The morning started with a session recapping highlights of the meeting from Sunday. Dr. Ivan Borello from the Johns Hopkins University School of Medicine was invited to give a 15-minute presentation recapping the myeloma highlights (see Part 1 and Part 2 of The Beacon’s Day Three update for more information).
The rest of the myeloma-related information was presented during poster sessions in the morning and afternoon. The highlights included results from a number of clinical trials studying potential new drugs for the treatment of myeloma, information about a couple of clinical trials that are still recruiting participants, and an analysis of secondary cancers in patients treated with Revlimid (lenalidomide).
One of the posters was on pomalidomide (CC-4047), a drug chemically related to Revlimid and thalidomide (Thalomid) that is being developed by Celgene for the treatment of multiple myeloma and related blood disorders. Pomalidomide and carfilzomib are the two new myeloma drugs that are furthest along in clinical trials and most likely to be approved for use in the United States soon. Preliminary results from the Phase 2 study presented during the poster session showed that pomalidomide plus dexamethasone (Decadron) is effective in relapsed myeloma patients, including those previously treated with Revlimid (abstract). Among the 61 participants, 35 percent responded, most within the first or second cycle of therapy. After about four months, almost all participants (97 percent) were still alive and two-thirds had not yet progressed. Side effects mainly included low blood cell counts and a few cases of fatigue, blood clots, high blood sugar levels, and pneumonia.
There were also two posters on elotuzumab, a new drug that is being developed by Bristol-Myers Squibb for the treatment of multiple myeloma. One of the posters included results from a Phase 1 study of elotuzumab, Revlimid, and low-dose dexamethasone in 29 relapsed / refractory myeloma patients (abstract). Three doses of elotuzumab were tested. The overall response rate was 82 percent for all patients and 95 percent for Revlimid-naïve patients. At the highest dose tested, most patients had still not progressed after 16 months of follow-up. The combination was generally well tolerated with serious side effects mainly limited to low blood cell counts due to Revlimid and infusion site reactions during the first cycle due to elotuzumab. Other common side effects included fatigue, diarrhea, nausea, and constipation. The middle dose of elotuzumab appeared to have a slightly better response rate than the highest dose, so a Phase 2 study that was presented yesterday during the oral session is currently further evaluating the middle and highest doses.
Another study presented during the session helped provide a better understanding of how elotuzumab works (abstract). Elotuzumab recognizes certain proteins called CS1 that are on the surface of myeloma cells, but not on normal cells. Scientists believe this recognition then triggers immune cells known as natural killer cells to kill the myeloma cells. The study suggests that elotuzumab also directly activates natural killer cells by recognizing the same CS1 proteins on the surface of the natural killer cells. Once elotuzumab activates these natural killer cells, they then appear to kill the myeloma cells.
There were also two posters on panobinostat (Farydak), an oral drug being developed by Novartis for the treatment of a number of solid tumors and blood cancers, including multiple myeloma. One of the posters included results from a Phase 1b study of panobinostat plus Velcade (bortezomib), and in some cases dexamethasone, in 62 relapsed / refractory myeloma patients (abstract). The optimal dosing determined during this trial was 20 mg panobinostat three times a week for two weeks followed by a week off. The overall response rate was 55 percent, and 40 percent of Velcade-refractory patients achieved a partial response. Serious side effects were mostly low blood cell counts, but some patients also experienced severe weakness. Other common side effects included gastrointestinal issues, nausea, fatigue, fever, dizziness, respiratory issues, and peripheral neuropathy (pain and tingling in the extremities).
The other panobinostat poster highlighted a large Phase 3 clinical trial that is still in progress (abstract). The trial is further studying whether the addition of panobinostat improves the efficacy of Velcade plus dexamethasone. The investigators are still looking to enroll another 270 relapsed / refractory myeloma patients who have received one to three prior therapies. For more information, see the clinical trial description.
There was also another poster highlighting an ongoing Phase 3 clinical trial. This one is studying whether the addition of carfilzomib, a new agent being developed by Onyx Pharmaceuticals, improves the efficacy of Revlimid and dexamethasone in relapsed myeloma (abstract). This combination is of particular interest because Velcade-Revlimid-dexamethasone is extremely effective; however, some patients have difficulty tolerating the peripheral neuropathy that can accompany Velcade therapy. Carfilzomib, which works similarly to Velcade, appears to be more tolerable. The study investigators are still looking to enroll another 550 relapsed / refractory myeloma patients who have received one to three prior therapies. For more information, see the clinical trial description.
There was also a poster on the topic of Revlimid and secondary cancers, a topic that was discussed in detail during the previous day of the meeting (see related Beacon news). The study presented during the poster session was an analysis of 11 Celgene-sponsored studies in which relapsed / refractory myeloma patients were treated with Revlimid or Revlimid plus dexamethasone (abstract).
Among the 3,839 patients included in the analysis, 57 cases of secondary cancers were reported. Taking into account how long the patients were treated or followed, 2.08 percent of them developed a secondary cancer each year. The rate of patients developing secondary cancers was similar regardless of length of time on therapy; however, there appeared to be a slight trend toward higher risk with longer therapy. The risk was also slightly, but not significantly, higher for patients who had undergone a prior stem cell transplant.
After a median follow-up of almost five years, 4 percent of participants had developed a second blood-related cancer, 10 percent developed a solid tumor, and 24 percent died, showing that myeloma patients are at greater risk of dying from myeloma or other causes than developing a second cancer. At three years, the overall survival was similar between patients who developed a secondary cancer and those who did not.
The study investigators concluded that the benefit-risk profile for Revlimid therapy remains strongly positive but that there are a number of limitations to the ways in which secondary cancers are tracked that may have affected their analysis.
Further details about Monday’s sessions are available in The Myeloma Beacon’s extensive Day 4 coverage in the Beacon multiple myeloma forums. Additional coverage of key research results from the meeting will continue throughout the rest of the week in individual, topic-specific news articles. For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2011 coverage.
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