June 6, 2011

Day 3 Updates from ASCO

Welcome to the final day of live coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Today, a poster session on multiple myeloma covered new drugs in development; refinement of the regimen for Velcade-based treatments; and additional data from the landmark MRC trial looking at the use of bisphosphonates.

Data for several new drugs in development were presented during this poster session, including panobinostat, pomalidomide, elotuzumab, and Treanda (bendamustine), all of which have been and/or are being studied in MMRC-facilitated clinical trials. First, Dr. Jesus San Miguel and colleagues presented data from a phase Ib study of panobinostat combined with a lower dose of Velcade that showed synergy between the two drugs in terms of efficacy and a lower incidence of peripheral neuropathy. Pomalidomide, which is in late-stage development for myeloma, showed encouraging activity when combined with low-dose dexamethasone in a large phase II study of heavily pretreated patients (including those refractory to both Revlimid and Velcade), and phase I data from the phase I/II study of elotuzumab combined with Revlimid and dexamethasone, presented during yesterday’s myeloma oral session, again showed encouraging data for this agent. Finally, Dr. James Berenson reported promising preliminary efficacy and safety from a phase I/II study of Treanda plus a reduced dose of Velcade, which, similar to Dr. San Miguel’s trial, appears to reduce the occurrence of peripheral neuropathy.

A poster by Dr. Nikhil Munshi and colleagues reported on a study of once-weekly Velcade dosing in the upfront setting for newly diagnosed myeloma patients not eligible for transplant. His data strongly suggest that a once-weekly regimen for four weeks with one week off reduced the risk of peripheral neuropathy. The authors suggested that this treatment regimen should allow for Velcade use as maintenance therapy.

A poster by Dr. Ruben Niesvizky and colleagues described a sub-analysis of the UPFRONT study, which compared three different Velcade regimens for patients with newly diagnosed myeloma. Dr. Niesvizky examined the impact of various baseline characteristics of patients, including age, sex, the presence of comorbid illness, and International Staging System (ISS) score, on the safety and efficacy of these regimens. While Velcade was active in all patient subgroups based on these characteristics, the likelihood of achieving a VGPR or better was higher in patients under age 75, and there were also significantly fewer adverse events in these patients. Similarly, CR and nCR rates were significantly higher for patients with no comorbidities; VGPR rates also tended to be higher for these patients, but the difference was not significant. Velcade had similar safety and efficacy regardless of sex and ISS score. These results demonstrate the ability of Velcade to overcome multiple risk factors, but they also highlight once again the ongoing need for improved treatment options for elderly patients.

We reported yesterday on two oral presentations describing sub-analyses from the MRC Myeloma IX study of Zometa versus clodronate in upfront multiple myeloma; today, a poster by Dr. Faith Davies again suggested that early and ongoing use of Zometa reduced the incidence of skeletal-related events (SREs) for newly diagnosed myeloma patients and improved OS in patients presenting with bone disease. However, incidence of osteonecrosis of the jaw (ONJ) was significantly increased in patients receiving Zometa after about 3.5 years of follow-up, ONJ occurred in about 3.5% of patients compared to about 0.3% in patients receiving clodronate. The authors reported that these were mild to moderate in severity. But, as Dr. Roodman mentioned the day before, given the preliminary data and increased incidence of ONJ, it would be premature to refine any guidelines around bisphosphonate use at this time.