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Mesenchymal stem cells didn't help prevent decompensation events in heart failure with reduced ejection fraction, the DREAM-HF randomized trial showed.

A single intracardiac dose of rexlemestrocel-L had no impact on the cumulative rate of recurrent non-fatal decompensation heart failure events compared with a sham injection over 30 months (HR 1.2, 95% 0.8-1.7), reported Emerson Perin, MD, PhD, of the Texas Heart Institute in Houston, at the American Heart Association (AHA) virtual meeting.

The trial also failed on the key secondary endpoints: time-to-first terminal cardiac event (ventricular assist device implantation, heart transplant, placement of an artificial heart, or cardiac death) and time to all-cause death.

However, there were signals of benefit in other secondary endpoints.

The stem cells reduced the composite of non-fatal myocardial infarction (MI) and non-fatal stroke by a relative 65% (4.6% vs 13.0% with the sham injection, P=0.001) and the exploratory post hoc composite endpoint of those events plus cardiac death by a relative 33% (20.3% vs 30.1%, P=0.021), which was entirely accounted for by those with inflammation marked by high-sensitivity C-reactive protein of at least 2 mg/L.

Reductions in cardiac death were seen in New York Heart Association (NYHA) class II patients by 57% (8.0% vs 19.8%, P=0.044), which again was accounted for entirely by the elevated inflammation subgroup.

"I think people should be excited about this. This is the largest study in cell therapy that's ever been performed, and with a very long follow-up of a mean of 30 months," Perin told 番茄社区app at an AHA press conference. "Even though we didn't look for multiplicity, you can look at the hazard ratios and these findings are quite significant and impactful."

While "interesting," the "subgroups with 'significant benefit' don't necessarily make sense," said late-breaking clinical trial session discussant Larry Allen, MD, MHS, of the University of Colorado in Aurora.

The positive findings largely relied on small numbers of patients and could also have been due to rates being higher than expected in the control patients, cautioned AHA press conference discussant Biykem Bozkurt, MD, PhD, of Baylor College of Medicine in Houston.

Still, "there is definitely a need to do more research for us to understand, because I think this is going to be very useful, not solely in the context of myopathies but both ischemic disease and atherosclerotic cardiovascular disease," she said.

Allen agreed on continued investment despite the lackluster results and with stem cell treatments in cardiology over the years.

"Failure of one approach does not condemn an entire heterogeneous field," he said. At the same time, "patients should understand stem cells remain experimental" and that "current treatments are unlikely to help them individually."

The included 537 patients with NYHA class II or III symptoms from ischemic or nonischemic heart failure. They were an elevated-risk group based on at least one heart failure hospitalization or outpatient visit requiring IV diuretics or vasodilators, or positive inotropic therapy between 1 and 9 months before study entry or elevated NT-pro-BNP levels.

They were randomized to a sham injection, or to at least one injection of 150 million allogeneic STRO-1/STRO-3+ cells from adult human bone marrow, targeted for transendocardial injection to a site of viable -- but inflamed -- myocardium identified by left ventricular electromechanical mapping.

Adverse events, both treatment-emergent and serious, came out similar between groups without any HLA reactions or clinically meaningful immune responses. One case of left ventricular perforation occurred during left ventricular mapping, for an incidence of 0.4%.

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