December 13, 2011

MMRF Newsflash from ASH

This final day of ASH 2011 brought us some interesting retrospective and follow-up analyses of prior MM studies, which addressed several key questions in myeloma treatment.

We cite two below:

First, Dr. Hervé Avet-L’oiseau presented a pooled analysis of almost 2000 patients treated with various regimens by the Intergroupe Francophone du Myélome (IFM) to analyze the impact of cytogenetics on prognosis and outcome for elderly patients. Dr. Avet-L’oiseau reported that the translocation of chromosomes 4 and 14 or t(4;14)was significantly less common in elderly patients (>65 years) compared to younger patients, while the deletion of chromosome 13 - del(13) - and the deletion of part of chromosome 17 -del(17p) – frequencies were similar. As is the case with younger patients, a negative survival impact was observed for patients with (4;14) or del(17p), regardless of treatment.

Second, Dr. Antonio Palumbo provided further data on the frequency of second primary malignancies (SPMs) in patients treated with Revlimid, using a pooled analysis of 9 clinical trials conducted by the European Myeloma Network, and consisting of approximately 2200 patients with at least one year of follow-up. Dr. Palumbo cautioned that, due to very small numbers of patients with SPMs, the findings must be interpreted with caution; however following a median of about 3 years of follow-up, data suggest that patients who received melphalan in combination with an immunomodulatory agent (Revlimid or Thalomid) approximately doubled their risk of an SPM. Dr. Palumbo noted that the resulting incidence rate was still quite low and that all incidences were similar to that expected for the general population. Dr. Palumbo emphasized that the risk of death due to treatment toxicity was actually higher than the risk of SPM, and he reiterated that the risk of disease progression is much more significant, at 10 to 15 times the risk of an SPM. He concluded that, according to evidence currently available and at the current follow-up of 3 years, the benefits of treatment outweigh the risks, particularly when there has been an overall survival benefit seen in some trials when Revlimid is used as maintenance. Dr. Palumbo encouraged ongoing study of this important issue.

Finally, our own Sandra Wear, Associate Director of Operations at the MMRC, presented metrics affirming the MMRC’s speed at opening and closing clinical trials based on a retrospective review of 25 multiple myeloma trials conducted with MMRC project management resources from May 2006 to July 2011. The data also included comparisons between a set of baseline trials (June 2006 - September 2008) and recent trials (September 2008 - July 2011) run through the Consortium, with the recent trials based on the model the MMRC and MMRF have established to accelerate drug development.

  • The recent trials opened 28% faster than the baseline trials, which opened at times consistent with industry standards (131 calendar days for recent trials vs. 181 calendar days for baseline trials);
  • All MMRC trials opened 20% faster when comparing all participating MMRC centers on any MMRC trial (189 days for recent trials vs. 236 calendar days for baseline trials);
  • MMRC trials enrolled 10% more patients than their pre-study enrollment commitment, with 89% of trials meeting their commitment; and
  • MMRC trials enrolled patients 10% faster when compared to their baseline enrollment timeline, with 67% of trials meeting their pre-study enrollment commitment 34%, or 4.5 months, faster than their baseline enrollment timeline.

With these strong metrics, working in collaboration with our investigators and industry partners, we have accelerated the development of several important treatments in late-stage clinical trials such as carfilzomib, elotuzumab, pomalidomide, and Zolinza, all of which were the focus of ASH abstracts at this year’s meeting.