December 7, 2009

Homing in on answers related to optimal combinations for induction therapy and the role of maintenance, Anne Quinn Young, MPH

Yesterday, more than 6,000 attendees packed into a hall the size of a small airport to hear Dr. Maria-Victoria Mateos from Dr. Jesus San Miguel’s group in Salamanca, Spain, deliver her plenary presentation at the ASH meeting. Just six abstracts out of thousands submitted for consideration are selected for plenary presentations at the meeting, so the myeloma community was thrilled that one of the six this year focused on our disease. The trial she presented built on the knowledge from the VISTA trial, which showed the overwhelming superiority of Velcade plus melphalan-prednisone versus melphalan-prednisone. The objective was to determine whether the best partner for Velcade was an IMiD (in this case, Thalomid – the only IMiD available in Spain when the study began) or an alkylator (in this case, melphalan) and whether there was a benefit to maintenance therapy. The results indicated that both combinations (VMP and VTP) had high response rates, include a high complete response (CR) rate, but VMP had fewer side effects. Furthermore, maintenance therapy – further bolstered the already high CR and near CR rates. Mateos also looked at using weekly Velcade which yielded high response rates while cutting the rate of peripheral neuropathy in half.

Following Mateos’s presentation were a series of abstracts looking at different induction regimens prior to high dose chemotherapy and stem cell transplant. For the most part, the results were preliminary as the trials were either phase I/II trials or had not reached endpoints like median time to progression or overall survival. Though the data are preliminary, several themes emerged though in all of these cases, more data are needed:

  1. Maintenance therapy appears to enhance the depth of response
  2. Weekly Velcade may provide similar benefit but with a lower rate of neuropathy
  3. It is not yet clear whether 3 or 4 drugs need to be combined upfront to maximize outcomes – data are not yet mature enough to show the benefits outweigh the added toxicities
  4. Data continue to indicate that Velcade overcomes adverse outcomes previously associated with certain genetic abnormalities such as the translocation of chromosomes 4 and 14

Finally, it is critical to note that none of the larger European trials included Revlimid as it was not available when these trials began several years ago so the regimens tested are not indicative of current standards of care in the US. We are fortunate that treatment options continue to evolve but this means that at times, when large phase III trials are finally completed, one or more of the treatment regimens tested may no longer represent a reasonable standard of care.

The take home message is that while we don’t yet know the “best” regimen for untreated myeloma patients – whether they are transplant candidates or not – there are a number of important ongoing trials that will help us to answer this question. In the meantime, if you’re eligible, consider enrolling in a clinical trial to speed the pace of these trials for the benefit of the entire community.