Dr. Robert Kyle is a multiple myeloma key opinion leader, physician, researcher, and professor at the Mayo Clinic. Dr. Kyle has dedicated his life to caring for multiple myeloma patients and studying the disease.

His work in myeloma began with his residency at the Mayo Clinic in the late 1950s, where he measured monoclonal protein levels in more than 6,500 myeloma and non-myeloma patients to identify a spike characteristic of multiple myeloma. He has authored more than 850 research papers and won lifetime achievement awards from the International Myeloma Foundation and the American Society of Hematology. In a 2003 editorial in Mayo Clinical Proceedings (PDF), Dr. Kenneth Anderson of Boston’s Dana-Farber Cancer Institute called Dr. Kyle “the world’s foremost expert” on multiple myeloma.

In an interview with The Myeloma Beacon, Dr. Kyle spoke about his approach to treating multiple myeloma patients; participation in clinical trials; many of the key issues for myeloma patients and physicians, including conventional and alternative treatment options; and the future of personalized medicine. This article, part one of a series of two, will cover Dr. Kyle’s approach to treatment. Part two covers the key issues and promising multiple myeloma therapies that Dr. Kyle suggested need further study.

Monoclonal Gammopathy Of Undetermined Significance And Smoldering Multiple Myeloma

During his interview with The Myeloma Beacon, Dr. Kyle first discussed the conditions that often lead to active multiple myeloma: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. Dr. Kyle was the first to describe MGUS and smoldering myeloma more than 30 years ago and has published many articles about both conditions since then.

Patients who have small amounts of monoclonal protein in the blood or urine are diagnosed with MGUS, he explained. If the amount of protein is larger, but the patient is asymptomatic, then the patient is designated as having smoldering multiple myeloma. Patients with symptoms are diagnosed with symptomatic multiple myeloma.

Dr. Kyle advised, “If the patient has smoldering, asymptomatic multiple myeloma, then it’s in the patient’s best interest not to treat because at the end of five years of observation, half of those patients will still be smoldering.” He added, “There are adverse side effects to any drug that you take. There’s also the cost to consider. So you’re much better off if you don’t have to take anything.”

There are some exceptions, however.  Patients with so-called “high-risk” smoldering multiple myeloma are likely to progress to symptomatic multiple myeloma within 6 to 12 months.

“Treating those patients before they develop problems with the disease is something to seriously consider,” said Dr. Kyle. He also said that a clinical trial is needed to compare survival in smoldering myeloma patients at high risk for progression between those who do and do not receive treatment.

Active Multiple Myeloma

Myeloma patients with symptoms such as anemia, pain from destruction of the bone, or an elevated calcium or creatinine level in their blood need to be treated.

“When treatment is needed, the first thing you need to decide upon is whether the patient is a candidate for an autologous stem cell transplant,” Dr. Kyle said. “If the patient is a candidate for the transplant, then one treats the patient with drugs that will reduce or kill the plasma cells in the bone marrow and not damage the stem cells.” He said most physicians will use dexamethasone (Decadron) along with thalidomide (Thalomid), Velcade (bortezomib), or Revlimid (lenalidomide). After three to four months of treatment, stem cells are collected. After collection, the patient can either continue with their original drugs or have the transplant.

Those who are not candidates for autologous stem cell transplants can be treated with melphalan (Alkeran), prednisone, and thalidomide or melphalan, prednisone, and Velcade, according to a review article by Dr. Kyle and his colleague published in August in the journal Clinical Lymphoma and Myeloma (abstract).

Another important consideration during treatment is a person’s individual genetic makeup. Dr. Kyle explained that patients with certain chromosomal abnormalities indicating poorer prognoses are “generally best treated with a Velcade-containing regimen.”

Myeloma doctors and researchers know from experience that Velcade appears to overcome the negative effects of chromosomal abnormalities. However, professional opinion is “mixed” about whether Revlimid might do the same: “We just haven’t had enough experience yet to know,” said Dr. Kyle.

Relapsed Multiple Myeloma

Dr. Kyle also discussed how he treats patients with relapsed multiple myeloma, a vital topic because almost all people who are treated for myeloma eventually relapse. When choosing a treatment regimen for a relapsed patient, “a very important consideration would be the treatment that the patient had before and how long that treatment lasted,” he said. “When a patient is treated with a drug or a combination of drugs, you need to give several courses of the drug to know whether the patient is going to respond. Generally, three or four months of therapy are necessary.”

“If that patient responds to the regimen, one generally treats the patient to the point of maximum response, provided they can tolerate the medication,” he said. “The treatment would then be stopped, and the patient would be observed without treatment.”

“If that patient remains in a response state for more than six months or, particularly, for more than a year after therapy has been discontinued, and the disease comes back at that time, then one would give that initial therapy again because the likelihood of that patient responding would be better than average with a different drug,” he said. “Also, the patient has already received that drug and knows they can tolerate it.”

However, people usually have a shorter and less effective response to a second round of therapy. Dr. Kyle explained that if a patient has a relapse within three or four months of his last treatment, “then the patient needs to go on to a new drug or a new combination of drugs.”

For more information please see part two of this series, in which Dr. Kyle discusses other myeloma treatments that still require further study.