If the disease is especially aggressive, Dr Korde said, carfilzomib is considered the best choice, either alone or in combination with a steroid or an immune-modulating agent. In contrast, elotuzumab and panobinostat “tend not to give great responses by themselves,” but when combined with other drugs, act synergistically against this cancer.

Although side effects differ for the 3 regimens, the approval of panobinostat from the U.S. Food and Drug Administration came with a black box warning for severe diarrhea and cardiac toxicities.3 These complications are, however, considered largely manageable with close monitoring and follow-up.

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The American Cancer Society estimates that in 2016, about 30,330 new cases of multiple myeloma will be diagnosed in the United States; of these patients, 12,650 are expected to die.

But with new treatment options, median overall survival for multiple myeloma improved from 3 years in the 1990s to about 7-to-10 years today.4 Researchers are also beginning to better understand the disease at the molecular level.

So far, KRAS and NRAS mutations are the most common genetic abnormalities identified, though no drugs yet exist that can target them, said Sham Mailankody, MD, another multiple myeloma specialist at Memorial Sloan Kettering. But drugs targeting BRAF mutations, which are approved for other cancers and occur in about 5% of multiple myeloma patients, seem promising and are being investigated in numerous studies, said Dr Mailankody in an email to Cancer Therapy Advisor.

Checkpoint inhibitors are also promising, as they work with the immune system to block mechanisms by which cancer cells shut off the immune system. Although there are no National Cancer Institute-directed clinical trials, Dr Sharon said, results from studies elsewhere are being monitored by the NCI.

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“We’re at the point with multiple myeloma that we’re talking about multiple diseases,” Dr Sharon said, adding that new tools are enabling investigators to better define these molecular differences than they were previously able to.

References

  1. Liu L, Zhao N, Xu W, Sheng Z, Wang L. Pooled analysis of the reports of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma. J Hematol Oncol. 2016;9(1):54. doi: 10.1186/s13045-016-0286-x
  2. Multiple Myeloma. American Cancer Society website. http://www.cancer.org/cancer/multiplemyeloma. Updated 2016. Accessed 2016.
  3. FDA approves Farydak for treatment of multiple myeloma. U.S. Food and Drug Administration website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435296.htm. Updated February 23, 2015. Accessed 2016.
  4. Lonial S, Boise LH, Kaufman J. How I treat high-risk myeloma. Blood. 2015 Sep 24;126(13):1536-43. doi: 10.1182/blood-2015-06-653261 [Epub ahead of print]

Topics:

Hematologic Cancers Multiple Myeloma