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AJMC Panel: Advances in Multiple Myeloma Therapy Extend Survival for Patients, Raising Cost Concerns

Written by Mary K. Caffrey, Produced by Nicole Beagin
It’s a concern that only comes when cancer therapy succeeds: as the length of survival for the typical multiple myeloma patient has nearly tripled, the number of patients living with the disease has also increased.1 Today, this blood cancer that was once a blip on the radar screen for insurers is slowly catching their attention as the cost of care increases, both for individual patients and gradually, across payment systems.

The American Journal of Managed Care recently convened a panel that included clinicians and representatives from the payer community and the Multiple Myeloma Research Foundation (MMRF). The group discussed the rapid advances in diagnosis and treatment of the disease. But as patients are living longer and therapy regimens become more complex, the cost of care is rising for this still relatively uncommon blood cancer.

Joining moderator and AJMC co-editor- in-chief Michael Chernew, PhD, were Shaji K. Kumar, MD, professor of medicine, Mayo Clinic; Jack Goldberg, MD, clinical professor of medicine, Penn Presbyterian Medical Center; Gene Reeder, RPh, PhD, director, Managed Care Networks, Xcenda; and Anne Quinn Young, MPH, vice president, Development and Strategic Partnerships, MMRF.

According to the MMRF, about 24,000 new patients will be diagnosed in the United States in 2014.2 Over the past 2 decades, advances in therapy and the use of stem cell transplants have revolutionized care and increased average survival from 3 years to about 8 years, according to Kenneth Anderson, MD, director of the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute, who in March gave the multiple myeloma update at the 19th annual conference of the National Comprehensive Cancer Network (NCCN).3,4

Screening and Diagnosis

Chernew asked how diagnosis of multiple myeloma has changed, and what the optimal practice would be for early screening. Kumar said routine screening of everyone over a certain age was impractical, as it would identify persons for whom there were no therapeutic options, and “would only contribute to anxiety.”

That said, there is a group for whom the disease should be identified well before the onset of the “CRAB” criteria: elevated calcium levels, renal failure, anemia, and bone failure. “At that point it may be too late,” Kumar said. Techniques such as examining circulating tumor cells, while not new, are becoming more precise in their prognostic value. The challenge is finding the optimal way to identify patients with myeloma early. For years, advances in treatment of multiple myeloma stalled because of the very nature of the disease, which presents differently from patient to patient and thus was not a good candidate for investment by the pharmaceutical sector. But the advancement of genomics, in which researchers identify the mutations that cause the varieties of myeloma, is allowing multiple myeloma patients to join clinical trials of therapies aimed at mutations that occur across multiple cancers.

Potentially quite fruitful is the CoMMpass Study, an effort by the MMRF that Anne Quinn Young discussed. CoMMpass seeks to gather tissue from 1000 patients at diagnosis and at each time the patient experience a relapse. The effort, Young said, will yield data about 3 kinds of sequencing: whole genome, exome, and RNA. Hopefully, “this will help give us a better understanding of the natural history of the disease and give us some clues to better precision medicine approaches,” she said.

Getting an early diagnosis does not mean a patient must be treated, Goldberg said. “It means better outcomes,” he said. Even if treatment is not immediate, patients can make lifestyle changes such as eating healthier foods and avoiding alcohol. Finding the fine line in “smoldering” myeloma— the optimal time, after diagnosis but before symptoms appear, when treatment should start—remains the challenge.

While Goldberg is hopeful that biomarkers may someday help pinpoint that line, thus far some biomarkers under study “are not ready for prime time. “It may take years, he said, “before these experimental markers are going to be able to tell us what the future will be.”

A Revolution in Treatment

Kumar explained that treatment advances have 2 pathways: changes due to new therapies, and changes due to better understanding of multiple myeloma’s biology. New drugs such as bortezomib and thalidomide have already changed the treatment landscape for the disease. Excitement is building because there aren’t just several new drugs in the pipeline but multiple new drug classes. As at NCCN in March, Kumar spoke animatedly about the clinical trials involving monoclonal antibodies (elotuzumab and daratumumab).

“The second half of the story is the changing understanding of the science,” Kumar said. In the past, the approach to therapy was “hit and run,” but today, clinicians know that “the bottom line is that patients need a couple of years’ worth of therapy, or even more. This is dictated by the underlying biology,” he said, as myeloma must be treated chronically to keep it under control.

That is possible, Goldberg said, because the newer drugs are much less toxic than their predecessors. Longer treatment periods achieve a “deeper” response, and “That’s where the benefit has been seen the most,” he said.

A simple truth, he said, is that to treat a patient with cancer, “You’ve got to be able to deliver the drug.” If the side effects are so awful that the patient can’t tolerate them, then the therapy has limited value.

The challenges today, Goldberg said, often involve dosing, and how to use the growing number of options in combination. The concept of “minimum residual disease” or
MRD, is also new to myeloma, because until recently, patients never got to that point, he said.

Concerns for Payers

The evolution of multiple myeloma from hard-totreat blood cancer to a chronic disease means that it will likely become expensive for payers as patients live longer, Goldberg said, although this may be offset by more years of productivity and quality of life. Kumar noted that some drugs that treat the disease will soon come off patent, which will mitigate costs somewhat. But the clinicians explained that the complexity of the disease and its heterogeneity means that treatment will always be very individualized, and that many patients will be on multiple drugs at once.

Both Goldberg and Kumar said that thus far, insurers have largely not balked at paying for multiple myeloma therapies, with the possible exception of oral therapies. But they said that could change as monoclonal antibodies near approval, and the variety of available options increases again.

“The insurer market is concerned about all these things,” said Reeder. While it’s clear that patients have benefited, he said, payers will likely reach a point of determining which patients will benefit from which therapy, and establishing a “stopping rule” to handle requests to repeat therapies that have already failed.

Young said one outcome of the CoMMpass study will be its guidance for precision medicine. It will show which patients can be helped with drugs that are off-patent, as well as which patients only need perhaps 2 drugs.

The most important task, the panelists agreed, will be making improvements in tackling myeloma at the outset. Said Goldberg, “We have to figure out how to do the best job in the beginning.” EBO
References

1. Ramesh N, Haehle M. Multiple myeloma survival increased significantly the past 15 years, but unevenly across ethnic and age groups. The Myeloma Beacon. http:// www.myelomabeacon.com/news/2013/08/31/multiplemyeloma-survival-race-age/. Published August 31, 2013. Accessed June 6, 2014.

2. Newly diagnosed patients: what is multiple myeloma. Multiple Myeloma Research Foundation website. http://www.themmrf.org/living-withmultiple-myeloma/newly diagnosed-patients/whatis-multiple-myeloma/. Accessed June 6, 2014.

3. Caffrey MK. Promising news in treating multiple myeloma. Am J Manag Care. 2014;20(SP7)SP217.

4. Bench to bedside translational science doubling myeloma survival. Dana Farber/Harvard Cancer Center website. http://www.dfhcc.harvard.edu/news/news/article/3062/. Accessed June 6, 2014.
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