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According to a recent article in Bone Marrow Transplantation, a significant portion of patients with multiple myeloma who do not respond to induction therapy still respond to subsequent high-dose therapy and obtain long-term survival.

Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone.

One standard treatment approach for multiple myeloma is high-dose therapy followed by an autologous stem cell transplant. High-dose therapy (chemotherapy and/or radiation) kills more cancer cells than moderate doses. However, more healthy cells, including stem cells, are also killed due to the high doses, often causing significant side effects. Stem cells are immature blood cells produced in the bone marrow that mature into red blood cells, which carry oxygen to tissues; white blood cells, which fight infection; and platelets, which aid the blood in clotting. Autologous stem cell transplants involve the collection of patient’s stem cells prior to high-dose treatment and re-infusion following high-dose therapy to restore depleted blood cell levels.

Prior to the process of high-dose therapy and an autologous stem cell transplant, patients receive what is called “induction therapy”. Induction therapy typically consists of conventional doses of chemotherapy administered in an attempt to reduce the amount of cancer in a patient’s body prior to high-dose therapy. Patients often have their stem cells collected following induction therapy. Induction therapy may also reduce the amount of cancer cells contaminating the stem cell collection that will be re-infused into the patient and provide optimal chances that high-dose therapy will eliminate most of the remaining cancer cells.

Patients who do not respond to induction therapy are referred to as having primary refractory disease and are often not offered the option of high-dose therapy and a stem cell transplant, as it is commonly thought that these patients will not respond to the higher doses of therapy. Furthermore, many insurance companies refuse to pay for high-dose treatment in patients with primary refractory disease.

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Researchers from England recently evaluated the outcomes of over 200 patients with multiple myeloma who underwent high-dose chemotherapy and an autologous stem cell transplant. Of these patients, 81% of patients achieved an anti-cancer response following induction therapy and 19% of patients did not achieve anti-cancer responses following induction therapy. All patients underwent subsequent high-dose therapy and an autologous stem cell transplant, despite their reaction to induction therapy. Following high-dose chemotherapy, a complete disappearance of detectable cancer (complete remission) occurred in 53% of patients who achieved an anti-cancer response following induction therapy, compared to 40% of patients who did not achieve an anti-cancer response to induction therapy. Overall survival following a complete remission achieved by high-dose therapy was equivalent between patients regardless of whether induction therapy provided an initial response. In addition, 5-year survival following a partial remission achieved by high-dose therapy was independent of a response achieved by induction therapy.

These researchers concluded that these results are not consistent with the thought that multiple myeloma patients who do not respond to initial induction therapy will not benefit from high-dose therapy. In fact, a substantial portion of patients who did not respond to induction therapy achieved a complete remission with high-dose therapy and demonstrated similar long-term survival to patients who did respond to induction therapy. Patients with multiple myeloma who are to undergo high-dose chemotherapy and an autologous stem cell transplant or who did not respond to induction therapy may wish to speak with their physician about the results of this study or the risks and benefits of participation in a clinical trial further evaluating this or other treatment approaches.

Reference: Singhala S, Powles R, Sirohi B, et al. Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma.

Bone Marrow Transplantation. 2002;30: 673-679.

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