The development of more effective treatment for multiple myeloma requires that new and innovative therapies be evaluated with cancer patients. Future progress in the treatment of multiple myeloma will result from the continued evaluation of new treatments in clinical trials.
Patients may gain access to better treatments by participating in a clinical trial. Participation in a clinical trial also contributes to the cancer community’s understanding of optimal cancer care and may lead to better standard treatments. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of multiple myeloma include some of the the following:
Multiple Myeloma News: The Daily Cancer News reports on all advances in the management of multiple myeloma that are most important to patients; visit the news to stay current with developments in the treatment of multiple myeloma.
New Drugs in Development: The introduction of Thalomid®, Revlimid®, and Velcade® has improved the treatment of multiple myeloma. Nevertheless, the optimal approach to using these drugs has not been established and researchers continue to evaluate different ways of combining these drugs with each other and with other myeloma therapies in order to further improve outcomes.
Panobinostat is a drug that belongs to a class of drugs called histone deacetylase (HDAC) inhibitors. They work by increasing the production of proteins that slow cell division and cause cell death. Adding panobinostat to Velcade® and dexamethasone is reported to improve the time to cancer progression from 8 to 12 months with over twice as many patients surviving 2 years. Longer follow up is required to determine any overall survival benefit.20
Kyprolis® (carfilzomib) belongs to a class of drugs known as proteasome inhibitors. They work by preventing the breakdown of protein in cancer cells, triggering their death. Patients with advanced myeloma treated with Kyprolis® in combination with Revlimid® and low-dose dexamethasone lived on average 26.3 months without their disease worsening compared to 17.6 months for patients treated with Revlimid® and low-dose dexamethasone.21
Elotuzumab is an investigational humanized monoclonal antibody, which binds to a protein (the CS1 glycoprotein) commonly found on myeloma cells and rarely found on normal cells. This treatment allows the immune system to selectively kill myeloma cells.
The FDA granted Breakthrough Therapy Designation to accelerate development because Elotuzumab, in combination with Revlimid® and low-dose dexamethasone, was proven active against relapsed multiple myeloma. Overall, 82% of patients in the trial responded to treatment.22
Pomalyst is an immunomodulatory drug that works by directly inhibiting angiogenesis and myeloma cell growth. Pomalyst alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone.23
Ixazomib is an investigational, oral proteasome inhibitor that also has promising anti-myeloma effects and low rates of peripheral neuropathy. Velcade® was the first in a new class of anticancer agents known as proteasome inhibitors to be approved for the treatment of multiple myelomaand has become a standard of care as part of initial treatment. Velcade®, Revlimid®, and dexamethasone are highly effective treatments for newly diagnosed multiple myeloma. Substituting ixazomib for Velcade® allows for the creation of an oral drug regimen with it potential for improved patient convenience. In a clinical trial evaluating the oral regimen the therapy was generally well tolerated and 92% of patients experienced at least a partial disappearance of their cancer.24
Maintenance therapy: The administration of relatively low doses of anticancer drugs after an ASCT could extend the time before cancer progression or prevent relapses. Dexamethasone and interferon are two drugs that have been investigated as maintenance therapy, but benefits remain uncertain.
Researchers conducted a Phase III clinical trial in 614 patients under the age of 65 who had undergone ASCT for initial treatment of multiple myeloma and then treated either Revlimid® or a placebo. Treatment with Revlimid® delayed the progression of myeloma but did not prolong overall survival.
Progression-free survival was 46 months with Revlimid® and 24 months with placebo. Overall survival is ~ 81 months in both groups.25
Reduced Intensity Allogeneic Stem Cell Transplant:
Reduced Intensity Transplants: In an attempt to reduce treatment-related side effects, some researchers have explored the role of reduced-intensity (RIC) allogeneic stem cell transplantation. This approach carries a lower risk than conventional allogeneic stem cell transplant, but has also been linked with a higher risk of relapse.26, 27 Nevertheless, one small study has reported that ASCT followed by RIC allogeneic stem cell transplantation resulted in better overall survival than tandem ASCT.28
High-dose therapy followed by allogeneic stem cell transplant is currently the only potentially curative treatment for multiple myeloma. The high risk of serious complications, however, has prompted researchers to explore an alternative procedure known as a reduced-intensity allogeneic stem cell transplant. In a study of 24 patients with poor-risk, relapsed, or refractory multiple myeloma, the approach of starting with an autologous stem cell transplant and then performing a reduced-intensity allogeneic stem cell transplant (with stem cells from an unrelated donor) produced promising response rates with a lower risk of death from treatment.29
Donor lymphocyte infusions: Recent studies have indicated that patients with multiple myeloma who experience a recurrence after an allogeneic transplant achieved high response rates to donor lymphocyte infusions. Researchers from several transplant centers in Europe evaluated 27 patients with multiple myeloma who had a recurrence following treatment with HDC and an allogeneic SCT.
All of these patients received infusions of donor lymphocytes after recurrence of the cancer. Over half of the patients experienced a partial or complete disappearance of myeloma following the infusion. Unfortunately, graft-versus-host disease, a side effect caused by donor cells attacking healthy tissue of the patient, affected over 75% of these patients. The results of this study suggest that donor lymphocyte infusions may be beneficial to patients with multiple myeloma who have a recurrence after HDC and allogeneic stem cell transplant.30
Induction Therapy & Chemotherapy
High Dose Chemotherapy and Stem Cell Transplant
Managing Complications & Side Effects of Myeloma
Strategies to Improve Treatment
References
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