Cell therapy may benefit certain patients with heart failure, reduced ejection fraction
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Key takeaways:
- An autologous cell therapy for patients with certain kinds of heart failure was safe, but there were not enough events to determine efficacy.
- A new trial in a more refined patient population will be launched.
An autologous cell therapy was safe for patients with heart failure with reduced ejection fraction and showed a signal of benefit for patients with elevated baseline N-terminal pro-B-type natriuretic peptide, researchers reported.
The CardiAMP HF trial of the autologous bone marrow mononuclear cell therapy (CardiAMP, BioCardia) was stopped early because of slow enrollment and low event rates, and a new trial will commence for patients with HFrEF and elevated NT-proBNP, who showed the best response to the therapy, Amish Raval, MD, director of clinical cardiovascular research and professor of medicine at the University of Wisconsin-Madison, who presented the data at the Technology and Heart Failure Therapeutics (THT) annual meeting, told Healio.
The presentation included data from the first 110 patients with HFrEF and ischemic cardiomyopathy in the trial (mean age, 66 years; 91% men) testing the safety and efficacy of the therapy; patients were selected due to having potent bone marrow cells, Raval told Healio.
The primary outcome was a hierarchical endpoint of cardiac death equivalents (CV death, left ventricular assist device therapy or heart transplantation), nonfatal major adverse cardiac/cerebrovascular events and 6-minute walk distance.
Trial paused
“This is a one-time treatment, and the hope was to be part of the armamentarium on top of guideline-directed medical management,” Raval told Healio. “The trial was paused by the [data safety monitoring board]. At that point in time, the reasons for the pause was it was difficult to recruit people [during the COVID-19 pandemic] and that they wanted to collect more data on existing patients before making any decisions about how to proceed, in part because the event rates appeared to be low. The patients in both [the cell therapy and control] groups seemed to be doing better. So the sponsor then made the decision to unblind midway through the trial to study what the [data safety monitoring board] was looking at to make sure there were not any safety problems. It turned out that there were no safety concerns with the overall approach and the futility threshold that was prespecified for efficacy wasn’t actually crossed. It was more about practical futility in the sense that it was taking a long time and the event rates seemed low.”
At 12 months, the hierarchical endpoints were similar in both groups (cardiac death equivalents: cell therapy, 5.6%; control, 5.3%; nonfatal MACCE: cell therapy, 12.5%; control, 10.5%; 6-minute walk distance change from baseline: cell therapy, 36 m; control, 33 m; P = .64), though for the 92 patients who had 24-month data available, the cardiac death equivalents rate was lower by nearly 5 percentage points (8.3% vs. 13.2%; P > .05).
“What’s exciting is that if you look at those patients who had a NT-proBNP level that was greater than 500 pg/mL, we start to see a separation in the cardiac death equivalents and the nonfatal MACCE events,” Raval told Healio.
In a subgroup analysis of 54 patients with NT-proBNP greater than 500 pg/mL at baseline, at 24 months there was a strong trend favoring the cell therapy group in the primary hierarchical analysis (cardiac death equivalents: cell therapy, 2.9%; control, 21.1%; nonfatal MACCE: cell therapy, 20%; control, 26.3%; 6-minute walk distance change from baseline: cell therapy, 19 m; control, –3 m; P = .07). An analysis replacing change in 6-minute walk distance with change in Minnesota Living with Heart Failure Questionnaire score was significant (P = .026).
‘Pivot to a second trial’
“The decision has now been made to pivot to a second trial, the CardiAMP HF II trial, in which we will take patients with NYHA class II or III HF with ischemic etiology, do a bone marrow potency test and, ultimately, inject the cells using the BioCardia Helix catheter into to the border zone; all of that is the same,” Raval told Healio. “The difference is that we will only select those people who also have elevated NT-proBNP levels greater than 500 pg/mL. Maybe this will select a sicker population and we can demonstrate differences in the events.”
The new trial is needed because “we don’t have a clear answer of whether [the therapy] works or not,” Raval told Healio. “One thing we will be studying more closely is ventricular arrhythmias. Paradoxically, that was lower in the cell-treated group than in the control group (7% vs. 13%), the reasons for which are not understood. One would think injecting aliquots of cell material into pockets in the heart might actually cause arrhythmias, as has been shown in studies of other cell types. The numbers are small, but it is an interesting hypothesis to test in the second trial.”
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Raval A, et al. Day I poster abstracts. Presented at: Technology and Heart Failure Therapeutics (THT); March 4-6, 2024; Boston.
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