Muhammad A. Mir, MD, is assistant professor of medicine at the Penn State Hershey Cancer Institute in Hershey, PA. His primary research interests are hematopoietic stem cell transplants and targeted immunotherapies for lymphoid cancers. He was lead author of a retrospective analysis of trends and outcomes for allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with multiple myeloma at the Mayo Clinic in Rochester, MN.1 

Cancer Therapy Advisor: Has the emergence of proteasome inhibitors and immunomodulating drugs diminished the case for allo-HSCT in myeloma?

Dr Mir: Proteasome inhibitors and immunomodulators have re-organized the landscape in myeloma and changed it from a rapidly fatal cancer to a chronic malignancy—but one that is still incurable. These therapies complement each other but there are not enough data to formulate a standard-of-care combination with allo-HSCT yet. Their application in maintenance may be promising, as has been shown for auto-transplants. Newer agents, such as antibodies, are also going to further alter current standard combinations.

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Cancer Therapy Advisor: Allo-HSCT exploits graft-versus-tumor effects and offers at least the potential for durable immune-mediated disease control. But high treatment-related morbidity and mortality have discouraged its widespread use, and you and others have described allogeneic transplant for myeloma as “controversial at best.”

Can allo-HSCT cure myeloma? How have advances in detection of minimal residual disease affected the thinking about a myeloma cure?

Dr Mir: Allo-transplant, as with many other malignancies, remains the only curative therapy in myeloma. Multi-color flow-cytometry and other techniques to measure minimal residual disease have redefined what was previously considered cure (complete remission, or CR).

We now understand that many of these patients who initially achieve a CR have malignant clones lurking under the surface for commonly applied clinical tests such as detection of para-proteins, and that they may relapse. Transplant for any disease is only as good as the patient going into transplant. Obviously, patients with no evidence of disease will be best theoretical candidates for allo-transplant.

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Allo-transplant in myeloma was very attractive 20 years ago when no directed agents were available, especially if matched siblings could be found. There are 3 hindrances to allo-transplant in the present era: (1), treatment-related mortality of 20% or more; (2) advanced age of many patients (older than 65 years); and (3) a lack of experience for myeloma allo-transplant in most centers. Even experienced centers, such as Mayo Clinic, allo-transplant only 3 to 5 patients per year for myeloma.