At the recent XII International Myeloma Workshop (IMW), physicians addressed the ongoing "cure versus control" debate in treating multiple myeloma. Though it can seem like a philosophical matter, the debate is extremely important to patient care. Whether a doctor aims to cure the patient or to control the disease will affect the type of treatment selected.

Even though there is still no cure for multiple myeloma, many physicians believe that the long-term survival experienced by many patients is nearly the same as a cure. At the same time, the line between disease and remission is often difficult to distinguish, making "cure versus control" an especially difficult question.

To Sagar Lonial, M.D., the defining characteristic of a cured patient is one with as few remaining traces of the disease as possible, even down to a molecular level. Others, like Sundar Jagannath, M.D., believe that patients who live for 10 years with a good quality of life are as good as cured, even with residual disease.

The choice they make is between destroying the disease at any cost and removing enough of the disease to achieve a good quality of life.

The discussion was inspired by a recent article in the Mayo Clinic Proceedings ^[1] by S. Vincent Rajkumar, M.D. Rajkumar describes the “cure” philosophy as advocating the removal of disease by applying tough multi-drug, multi-transplant therapies, at the risk of side effects that could deteriorate the patient’s overall health. On the other hand, physicians whose aim is to “control” the disease approach the cancer as a chronic condition -- something to live with. Once the patient’s disease level is in the safe zone, these doctors focus on bringing the quality of life to a comfortable level.

In the article, Rajkumar argues against the standing convention of equating a CR (complete response) with having cured the disease. As he writes, CR “is the means to a goal, not the ultimate goal,” because patients who achieve a CR can later experience a relapse. Rajkumar calls a CR a marker that distinguishes those patients who demonstrate improved overall survival. In clinical trials, high CR rates often correlate with better overall survival, but they have not been shown to cause the improved survival rates.

The crux to his argument is that there is no evidence to show that achieving a CR actually improves a patient’s chances of survival and quality of life. As an example, he points to smoldering myeloma, a condition in which low levels of the same monoclonal protein found in myeloma results in few or no discernible symptoms. The characteristics of this condition are similar to residual disease in myeloma patients.

Jagannath points out that in a study of Army veterans only a small group of subjects with smoldering myeloma and its precursor condition went on to develop multiple myeloma. The Army study illustrates that, unlike leukemia or non-Hodgkin's lymphoma, where remission must be all-or-nothing, it is possible to live relatively unaffected by residual levels of myeloma.

"In myeloma, complete remission is not equivalent to cure," Jagannath says. He believes that a patient’s ability to live many years is a better definition of cure than elimination of the disease, and myeloma patients do not need to achieve complete remission in order to live many years.

To Lonial, however, "the first goal is to get to a CR and then the second goal is to try and maintain that CR."

Lonial believes that for high-risk patients in particular, CR is essential to long-term survival. Fifteen percent of myeloma patients are genetically classified as high risk; these patients more often relapse, even with very good partial responses to previous treatments. The chances are much better for high-risk myeloma patients who achieve a CR and follow with more aggressive maintenance therapies.

Both physicians acknowledge that the introduction of thalidomide ^[2] (Thalomid), Velcade ^[3] (bortezomib), and Revlimid ^[4] (lenalidomide) 10 years ago has given myeloma patients an unprecedented opportunity for long-term survival. According to Jagannath, as long as new drugs keep coming, patients will be able to try one and another until something works. Lonial puts store in the synergistic effect of multi-drug therapies, which is discussed in a previous Myeloma Beacon article ^[5].

"So, the question is," says Jagannath, "are we curing myeloma patients now?"

With the growing number of patients living 10 years past their initial diagnosis, he thinks yes.

To read more about the "cure versus control" debate, visit S. Vincent Rajkumar's article at the Mayo Clinic Proceedings ^[1] or refer to the IMW presentation transcript ^[6] (pdf) provided by the MMRF.