June 1, 2009

Update from the ASCO Annual Meeting: Cure vs. Control, Anne Quinn Young, MPH, Program Director

On Friday, the MMRF hosted its fifth CME symposium for physicians at the Annual ASCO Meeting. This year, the esteemed faculty included Chair of the Program, Ken Anderson, Dana-Farber Cancer Institute; Sergio Giralt, MD Anderson Cancer Center; Vincent Rajkumar, Mayo Clinic – Rochester; and Paul Richardson, Dana-Farber Cancer Institute. The program was entitled “Treatment of Multiple Myeloma: Cure vs. Control”, based on a thought-provoking paper from Dr. Rajkumar published last year in the Mayo Clinic Proceedings (http://www.mayoclinicproceedings.com/content/83/10/1142.long).

The presentations each addressed the question of whether, at each point in the disease course, the goal of therapy should focus on cure or control. There is consensus on the long-term goal being cure – that much is clear – but at each point, particularly as the disease progresses, there is far from unanimity on how aggressively clinicians should go for the cure – or at least a complete response – at the risk of increased toxicities and impaired quality of life. There does seem to be greater consensus with respect to high-risk patients, as they are more likely to relapse and data indicates that inducing a sustained complete response is critical in these patients. Similarly, there are emerging data to indicate that patients who do not necessarily achieve a CR can benefit from a sustained partial or even minimal response, as shown from a small number of patients who remained stable for a number of years on Revlimid as a single agent – without dex - despite never achieving a CR on therapy. Somewhat counter intuitively, it appears to be more beneficial to achieve a lower but durable response than a transient CR that is associated with rapid relapse (http://www.nature.com/nature/journal/v459/n7246/full/459508a.html).

The question of cure vs. control again emerged subtly in the Sunday morning oral presentations, and it is clear that there is not yet substantial data to help us understand which regimens can maximally delay disease progression and increase survival. It is clear that newer combinations – particularly three drug combinations such as RVd (Revlimid-Velcade-dex) and VMP (Velcade-melphalan-prednisone) are associated with 80-100% response rates, and up to 40% CR rates when used front-line, which is an exponential increase over older combinations such as MP and VAD, but these trials are so young that for many, median survival and time to disease progression, never mind overall survival, have not yet been reached.

Until we have these answers it is important that patients, particularly those who are newly diagnosed and untreated, consider one of the many clinical trials available (www.myelomatrials.org) so that we can answer these critical questions.In the meantime, it is also important to understand that three and four drug combinations are likely to confer the greatest benefit to patients, the trials have very short follow-up, and many have limited patients analyzed to date, so it is premature to make any conclusions about what the optimal combination, at any point, may be.