Dr. Kenneth Anderson is a multiple myeloma thought leader, physician and researcher at Dana-Farber Cancer Institute, where he is Director of the Jerome Lipper Multiple Myeloma Center. He also is the Kraft Family Professor of Medicine at Harvard Medical School in Boston.
Dr. Anderson’s research has played a key role in the development of several new multiple myeloma drugs and, more broadly, the significant improvement in treatment outcomes for myeloma patients that has occurred over the past 10 to 15 years.
In an interview with The Myeloma Beacon, Dr. Anderson spoke about his approach to treating multiple myeloma patients as well as the future of myeloma treatment and how this may lead to a cure for myeloma. This article, part one of a series of two, will cover Dr. Anderson’s approach to treating myeloma. Part two will cover Dr. Anderson’s thoughts on the future of myeloma treatment.
Combination Versus Sequence Therapy
When asked whether patients should begin treatment with a combination of therapies upfront or sequence novel agents to save options for a later relapse, Dr. Anderson stated, “There’s no question that we really should use combination therapies right from the start.”
“Now that we have defined active drugs, the best way to use them for sure is early in a cocktail,” explained Dr. Anderson.
He compared myeloma to tuberculosis and human immunodeficiency virus, in which patients can develop drug resistance if treated with sequential single drugs. Like with those diseases, Dr. Anderson said that myeloma patients should use combinations of drugs right from the start so that the disease will not become resistant to available treatments.
Dr. Anderson indicated that the best combination as of today is Revlimid (lenalidomide), Velcade (bortezomib), plus dexamethasone (Decadron), which achieves a 100 percent response rate (52 percent complete response, 22 percent very good partial response, and 26 percent partial response). “There are ongoing studies that are trying to improve upon that by adding a fourth drug, either a standard chemotherapy or other novel therapy,” Dr. Anderson added.
Stem Cell Transplantation
As more and more studies demonstrate a high frequency and long duration of response to novel myeloma agents such as Revlimid, thalidomide (Thalomid), and Velcade, the myeloma community is debating whether stem cell transplantation continues to be necessary for myeloma patients or whether treatment with novel agents is as effective.
Dr. Anderson stated that the current standard of care for multiple myeloma patients continues to include stem cell transplantation for those who are physically eligible for the process.
In particular, Dr. Anderson recommended participation in a clinical trial whenever possible. He also said that patients should receive initial treatment with Revlimid-dexamethasone or Velcade-dexamethasone, or Revlimid-Velcade-dexamethasone. Patients should then have their stem cells collected and proceed directly to treatment with high-dose melphalan (Alkeran) and transplantation using the patient’s own stem cells (autologous stem cell transplantation).
He specifically recommended, “All patients should receive novel agents as their initial treatment. In those patients who are transplant candidates, they should then go ahead and receive the transplant, followed by novel agents to consolidate and maintain the response to transplant.”
However, Dr. Anderson was extremely cautious about the use of allogeneic stem cell transplants, in which the stem cells come from a matched donor, due to the high risk of complications associated with this type of transplant.
Studies have shown that allogeneic stem cell transplantation is associated with long-term remission in myeloma patients. It is also the only potential cure at this time for multiple myeloma. Unique to a donor transplant, the donor stem cells may recognize the recipient’s myeloma cells as foreign and launch an immune attack on the myeloma cells. This is known as the graft-versus-myeloma effect.
Despite the long-term remission associated with donor transplants, Dr. Anderson stated, “We rarely use allogeneic transplantation in myeloma anymore.”
Just as the donor cells may recognize the recipient’s myeloma cells as foreign, the donor cells may also recognize the rest of the patient’s cells as foreign and launch an immune attack against them. This immune response, which is known as graft-versus-host disease, can cause severe skin, liver, and gut problems. It also contributes to the 10 percent to 20 percent mortality rate associated with donor transplants.
“Especially in the era of novel therapies, allogeneic transplantation is being used less commonly,” explained Dr. Anderson. “When used, it should be done nowadays only in the context of a clinical trial in order to exploit the graft-versus-myeloma effect while minimizing the toxicity.”
Dr. Anderson indicated that patients with multiply relapsed myeloma or those with very high-risk disease might be considered for donor transplantation.
Maintenance Therapy
Following stem cell transplantation, or initial therapy for those who are not transplant candidates, Dr. Anderson recommended maintenance therapy with Revlimid.
This recommendation is based on three clinical trials that have shown progression-free survival is significantly longer in patients who receive Revlimid maintenance.
Dr. Anderson said that early results have also indicated promising results for Velcade-thalidomide maintenance therapy in newly diagnosed elderly myeloma patients as well as Velcade maintenance after stem cell transplantation.
Bisphosphonates
Myeloma often causes bone complications, including holes in the bone or fractures. Bisphosphonates are used to slow or prevent this bone disease, thereby improving the quality of life of myeloma patients.
Research from this past year showed that Zometa (zoledronic acid) may also prolong survival of myeloma patients.
Dr. Anderson said that “Bisphosphonates are a very important supportive therapy for myeloma. It has been postulated for years that they may also have some anti-myeloma affect.” Despite the prolonged survival, Dr. Anderson said, “The primary use for bisphosphonates has been and always will be to abrogate bone disease.”
Implications For Myeloma Patients
Based on Dr. Anderson’s experience treating multiple myeloma patients, he said, “The median survival, especially in younger patients, is seven to eight years. Maintenance is adding at least another several years to that. So a newly diagnosed patient today has a likely median survival of over ten years.”