Treatment of Relapsed or Refractory Multiple Myeloma

This content has been reviewed and approved by

Kenneth C. Anderson, MD
Chief, Division of Hematologic Neoplasia

Dana-Farber Cancer Institute

Relapsed myeloma, also called recurrent myeloma, is multiple myeloma that returns after a successful course of treatment. Refractory myeloma is multiple myeloma that does not respond to treatment—whether initial therapy or therapy for recurrent disease.

If your multiple myeloma relapses more than 6 months after treatment, then your doctor can use the same therapy again. If it relapses sooner than that, or does not respond at all, there are several “second-line” therapies you can try. Your choice of therapy will depend on what treatment (or treatments) you have already had. Options include:

  • Velcade® (bortezomib) plus Doxil® (liposomal doxorubicin) - This combination was recently approved by the U.S. Food and Drug Administration (FDA) to treat relapsed or refractory multiple myeloma. Bortezomib is a targeted therapy that promotes the death of myeloma cells. Liposomal doxorubicin is a chemotherapy agent used to treat many types of cancer.
  • Revlimid® (lenalidomide) plus dexamethasone - This combination also was recently approved by the FDA to treat relapsed multiple myeloma. Lenalidomide is a targeted therapy similar to Thalomid® (thalidomide). Dexamethasone is a steroid medication.

Bortezomib With or Without Dexamethasone

  • Thalomid® (thalidomide) - This targeted therapy is often used as initial treatment for multiple myeloma. However, it may be used for relapsed disease as well. It may be used in combination with dexamethasone or the chemotherapy agent Alkeran® (melphalan).
  • Various combinations of dexamethasone and chemotherapy agents - A number of different anticancer chemotherapies may be used in combination with dexamethasone. Possibilities include:

    • Cyclophosphamide, vincristine, and Adriamycin® (doxorubicin hydrochloride)
    • High-dose cyclophosphamide
    • Cisplatin, doxorubicin hydrochloride, cyclophosphamide, etoposide, plus thalidomide
    • Cyclophosphamide, etoposide, Platinol® (cisplatin)

In many cases, the best treatment option for relapsed or refractory disease is enrollment in a clinical trial, a research study that involves patients. Researchers are investigating whether new treatment combinations may offer better results in controlling multiple myeloma. If your myeloma has relapsed or is not responding to treatment, you may wish to discuss clinical trials with your doctor.

Ongoing Research

Researchers are currently investigating new treatments for multiple myeloma. Participation in trials of these treatments will lead to improved therapies. If you wish to participate in a clinical trial, please talk to your doctor about the potential benefits and side effects of the treatment. Promising directions include the following:

  • New biologically targeted treatments – Biologically targeted treatments work by blocking tumor cells’ ability to grow and spread. Thalomid® (thalidomide), Revlimid® (lenalidomide), and Velcade® (bortezomib) are new treatments based on this concept. Researchers are investigating drugs that can prevent angiogenesis, which is the growth of new blood vessels that feed the cancer. Other new drugs target factors called cytokines, which stimulate bone destruction. Mutiple agents are undergoing clinical trials, both alone and in combinations, that offer great promise for treating recurrent myelomas as well as patients of all ages with newly diagnosed disease.
  • High-dose therapy and stem cell transplant - Researchers continue to conduct clinical trials of the best ways to use stem cell transplantation. Some are looking at whether two transplants performed within 6 months of each other—called “tandem” or double transplants—are better than a single transplant. Others are looking at whether a second round of high-dose therapy and stem cell transplantation can benefit patients who do not get enough benefit from the first procedure.
  • Allogeneic stem cell transplants - Clinical trials are researching new ways of using allogeneic stem cell transplants to treat multiple myeloma. These use stem cells from a donor, rather than the patient. One possibility involves using lower doses of chemotherapy and/or radiation therapy before the transplant.
  • Vaccines - Several clinical trials are ongoing to examine the possibility of vaccinating patients against their own cancer cells. Vaccine therapy tries to stimulate the immune system into defending the body against the cancer cells, without harming normal cells.
  • Maintenance therapy - Maintenance therapy is the practice of giving additional treatment to help “seal” the benefits of initial therapy. Thalidomide, lenalidomide, and bortezomide are under study.

Clinical trials of new treatments generally are conducted in three phases. Phase I trials are designed to figure out whether a new treatment can be given safely. It determines the best schedule and dosing levels, and also whether the side effects are tolerable. Phase II trials examine the how effective the new therapy is against myeloma in a larger number of patients. If phase I trials show safety and phase II trials show effectiveness against the disease, then phase III trials are done to compare the new therapy with the current standard treatment. If it proves superior, the next step is to obtain approval from the U.S. Food and Drug Administration for widescale use.

This content was last reviewed August 15, 2010 by Dr. Reshma L. Mahtani.
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