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In a Myeloma Setback, Merck Halts Studies Due to Patient Deaths

Xconomy New York — 

[Corrected, 11:10 a.m. ET, see below] Immunotherapy drugs known as checkpoint inhibitors have started to change how a variety of cancers are treated, but they have yet to break through in multiple myeloma, a progressive cancer of the bone marrow. There was a setback on that front today.

Merck (NYSE: MRK) Monday afternoon paused enrollment in two Phase 3 trials testing its immunotherapy drug, pembrolizumab (Keytruda), in combination with two established therapies, pomalidamide (Pomalyst) and dexamethasone, in patients with multiple myeloma. Merck stopped the trials, called Keynote-183 and Keynote-185, to collect more information and “better understand more reports of death” of the patients on its drug, according to a statement.

Merck didn’t disclose additional details, other than to say additional pembrolizumab studies continue unchanged. “The analyses need to be conducted,” said spokesperson Pam Eisele. But the news offers a fresh reminder of the unknowns and potential safety perils of combining immunotherapy drugs with other treatments to expand their reach. As Xconomy reported last month, with the frenzy to test such combinations, many cancer experts worry that the field is moving too fast; that studies are not being designed with enough care; and that the glut of combination trials is bound to provoke a backlash. Unexpected safety problems have popped up during certain tests.

Merck shares slid 1.2 percent in post-market trading on Monday.

In multiple myeloma, the bone marrow’s plasma cells—a type of immune cell that normally churns out infection-fighting antibodies—grow rapidly and abnormally and crowd out healthy red and white blood cells. According to the American Cancer Society, about 30,000 people in the U.S. will be diagnosed with multiple myeloma this year. It’s the third most common blood cancer in the country after lymphoma and leukemia.

[Corrected to include mention of elotuzumab] There are many treatment options available for myeloma—injectable antibody drugs, chemotherapies, pills, stem cell transplants, and more—and they’ve helped extend patients’ life expectancy dramatically from just a few decades ago. Yet there is no cure, and the disease progresses even if patients initially respond to treatment. Increasingly, immunotherapy has been gaining traction as a potential additional treatment option. In 2015, the FDA approved elotozumab (Empliciti), an immune system-boosting treatment for multiple myelom from Bristol-Myers Squibb (NYSE: BMY). Other immunotherapies have been creeping forward as well, among them the checkpoint inhibitors that made progress in a variety of other cancers.

One form of immunotherapy, a cell therapy technique known as CAR-T, has shown early promise in treating handfuls of multiple myeloma patients who have failed several prior therapies. Those tests are early, however. Checkpoint inhibitors, like pembrolizumab and Bristol-Myers’s nivolumab (Opdivo), are being tested too, and are further along. These drugs have been approved for lung, skin, bladder, and other cancers and have become the standard of care for some patients. While checkpoint inhibitors haven’t been effective on their own in multiple myeloma, they have shown positive signs when combined with existing treatment regimens. The latest results from Merck’s prior multiple myeloma study, Keynote-023, for example, were presented at the American Society of Clinical Oncology’s meeting earlier this month and showed that 44 percent of patients who could be evaluated responded to treatment with a combination of pembrolizumab, pomalidamide, and dexamethasone. Results from the Keynote-023 study have been published in the journal Blood.

That study didn’t reveal any unexpected dangerous side effects. As ISI Evercore analyst Umer Raffat wrote in a research note, there was “no clear hint in prior studies” of a new safety problem when combining Merck’s drug with pomalidomide and dexamethasone. Given Merck’s news today, such problems are worth watching with other, similar combination trials currently underway: Bristol-Myers has a Phase 3 trial, Checkmate-602, that began in April 2016, while AstraZeneca’s Phase 2 study, FusionMM-003, started last July, according to a note from Raffat.