Another Meeting, Another Mesenchymal Stem Cell Study (or Two), With Mixed Results
ROME, Italy—Another international cardiology meeting, another chance to peer glumly at some small studies with soft endpoints attempting to demonstrate a benefit of stem cells in cardiac regeneration. Two such studies were presented back-to-back this morning in the first Hotline session at the European Society of Cardiology Congress 2016.
In the first, CHART-1, Jozef Bartunek, MD (Cardiovascular Center, Aalst, Belgium) reported on the safety and efficacy of cardiopoeietic cells derived from patients mesenchymal stem cells (Ceylad; Mont St. Guibert, Belgium) used at 39 centers. For the primary endpoint—a hierarchical composite in which each individual patient is compared with all other patients, using the metrics of all-cause mortality, number of worsening HF events, quality of life, 6-minute walk test, and measure of LV function—investigators saw no difference between the 120 patients randomized to receive the cells versus the 151 given a sham procedure. Treatment through 39 weeks was safe, he added. Two exploratory analyses showed reductions in mortality and worsening heart failure in the cell-treated group among patients with the most severe heart enlargement (left ventricular end-diastolic volumes between 200 and 370 mL) at baseline.
In the second trial, Javed Butler, MD, PhD (Stony Brook University School of Medicine, NY), and colleagues reported the results of a 23-patient, single-blind, crossover study using direct myocardial injections of mesenchymal stem cells (MSCs) in patients with nonischemic heart failure. At 6 months, the therapy appeared to be safe based on Holter monitor, liver, kidney, and lung tests, Butler said. Six-minute walk test appeared significantly improved. No significant difference was seen between groups in terms of left ventricular function improvement. Investigators plan on proceeding to larger studies, with clinical endpoints, as well as testing the therapy in ischemic cardiomyopathy, potentially using repeat injections.
Not Getting Carried Away
Following the presentation of both trials in a morning press conference, session co-moderator Frank Ruschitzka, MD (University of Zurich, Switzerland), reminded reporters not to get “carried away” with exploratory analyses when the primary endpoint results were neutral. He, with co-moderator Mariell L. Jessup, MD (University of Pennsylvania, PA), conceded to TCTMD that stem cell studies in heart failure have had a long and checkered history, marked with slow progress, dashed hopes, and inconclusive studies.
This field of study “is not easy,” Jessup said. “I can understand why [journalists] may not want to keep covering this, but I think scientists need to keep chipping away at it, because it’s the Holy Grail. If we could regenerate the heart, that would solve many, many issues. But it’s very complex and we’ve tried to make it too easy just by taking cells and putting them in the heart. I think we’ve got a lot more to learn.”
Indeed, Ruschitzka observed that the “regeneration principle” at this stage “is literally off the table.” Now, he said, “I think it’s really a pleiotropic effect that we might want to speculate about. [But] if we were not so intrigued [and convinced that it is] good to embrace this idea, we wouldn’t have kept it alive for so long and even to accept it for a hotline.” For now, however, these studies remain “relatively small” and lack “conclusive data,” he concluded.
Butler pointed out that there are many studies still ongoing, but progress is slow. “These trials are very expensive, even the smaller ones, and we have to do these smaller studies first.”
Fifteen years of study is actually a relatively small time frame for this field of investigation, he added, noting that there are different kinds of cells, different doses, different delivery methods, and different target patient populations.
Indeed, Bartunek told TCTMD, results for the study he presented here today were actually 10 years in the making.
- Bartunek J. Congestive heart failure cardiopoietic regenerative therapy (CHART 1): Clinical trial primary outcomes. Presented at: European Society of Cardiology Congress 2016. August 28, 2016. Rome, Italy.
- Butler J, et al. Safety and preliminary efficacy of intravenous allogeneic mesenchymal stem cells in patients with non-ischemic heart failure. Presented at: European Society of Cardiology Congress 2016. August 28, 2016. Rome, Italy.
- Bartunek reports working at the institution that co-founded Ceylad.
- Butler reports consulting/royalties/ownership/stockholder payments from Bayer, Boehringer Ingelheim, Cardiocell, Gilead, Janssen, Merck, Novartis, Trevena, Relapsa, and Z Pharma.
- ‘Enhanced’ Multicellular Stem Cell Therapy Improves Clinical Outcomes in Heart Failure: ixCELL-DCM Study
- Intramyocardial Injection of Stem Cells Shows Promise for Severe Ischemic Heart Failure