Everyone wants to see an outright cure for cancer — but for multiple myeloma, scientists’ best tactic appears to be using a variety of tools to beat back the cancer and keep it in a holding pattern.
That is the tack taken in a recent clinical trial from City of Hope that showed promising results. Published Dec. 22, 2011, in Biology of Blood and Marrow Transplantation, the findings hint at a combination of treatments that could help many patients live longer with multiple myeloma, considered an incurable disease.
“Our challenge with multiple myeloma is the persistence of the disease despite therapy,” said lead author Firoozeh Sahebi, M.D., clinical associate professor in the Department of Hematology & Hematopoietic Cell Transplantation. But using a series of new treatments could both improve patients’ response and reduce side effects — potentially boosting long-term outcomes.
Multiple myeloma is a blood cancer that develops in the bone marrow. It affects plasma cells, the cells in the marrow that make antibodies to fight infection. These cells become cancerous and overgrow in the bone marrow, crowding out other normal blood cells. Physicians used to prescribe chemotherapy followed by hematopoietic transplantation, but a growing arsenal of drugs offer another approach.
Drugs called immunomodulating agents boost the immune system to fight cancer. These include thalidomide — a drug dating back to the 1950s — and lenalidomide. Other medications known as proteasome inhibitors, like Velcade (bortezomib), prevent elimination of waste products in the cancer cells, leading to cell death. Doctors increasingly have used these two types of drugs together to knock down and suppress multiple myeloma. More recently, they started to use them after stem cell transplant to keep cancer in check.
Research has shown that patients live longer when their treatment hits cancer hard and leads to what doctors call “complete response” — the total disappearance of signs of the disease. Therapeutic strategies like those tried at City of Hope may help more patients achieve complete response or near-complete (very good partial) response.
“If we can use a sequence of new therapies to dramatically reduce the number of cancer cells and suppress any of these cells that remain, research shows we can improve complete response rate and reduce the incidence of peripheral neuropathy, a common side effect with new anti-myeloma therapies,” Sahebi said.
City of Hope researchers enrolled 45 multiple myeloma patients in a phase II study assessing a potential maintenance strategy starting in 2008. The study aimed to put patients through high-dose chemotherapy followed by an autologous stem cell transplant, a procedure in which patients received their own previously collected stem cells. Then, patients got six cycles of once-a-week dexamethasone (a steroid) and bortezomib, followed by six cycles of weekly thalidomide and dexamethasone. Patients were then on thalidomide alone until their myeloma progressed.
Forty of the patients underwent transplantation. A year later, 20 of the patients were still in complete response and two had a very good partial response. They tolerated their treatment well.
“We see reasons for optimism,” said study co-author Amrita Krishnan, M.D., director of the Multiple Myeloma Program. “The study showed that maintenance therapy with bortezomib was well-tolerated and led to an increased rate of deeper responses, which we hope will ultimately translate into better survival.”
Sahebi was equally encouraged. In late January, the Food and Drug Administration approved the injection of bortezomib just under the skin, which means less nerve pain and other side effects for patients than when it is given intravenously. “We are eager to assess the long-term benefits of combining bortezomib with other therapies for multiple myeloma in the future,” she said.
Finding clues in the environment against multiple myeloma
As scientists build their understanding of multiple myeloma, they gain ideas for ways to fight it. One possible way is by targeting a growth factor that can help myeloma thrive.
Multiple myeloma, like many cancers, can be fueled by proteins found in the tissue around it — what scientists call the microenvironment. One of these is the vascular endothelial growth factor, or VEGF.
City of Hope’s George Somlo, M.D., professor in the departments of Medical Oncology and Therapeutics Research and Hematology & Hematopoietic Cell Transplantation, led a National Cancer Institute-supported California Cancer Consortium clinical trial that evaluated bevacizumab (Avastin) alone and in combination with thalidomide for multiple myeloma that had relapsed or resisted other treatment. Bevacizumab fights the production of VEGF.
While the study’s enrollment was small, Somlo noted in the study, published in 2011 in the British Journal of Haematology, that bevacizumab may hold promise when combined with other drugs against specific multiple myelomas that express high levels of VEGF. Several studies in multiple myeloma using drugs targeting the microenvironment are underway around the country.