Mixed Findings From ALLSTAR Trial of Stem Cell Therapy After Myocardial Infarction

Stem cell therapy to reverse damage to the heart following myocardial infarction (MI) has been an area of research for many years. Autologous cardiosphere-derived cells (CDCs) could offset pathologic processes that lead to post-MI cardiomyopathy. Indeed, CDCs have anti-inflammatory, antioxidative, and antiapoptotic properties that could delay or prevent enlargement of the heart.

Timothy D. Henry, MD, of Cedars-Sinai Heart Institute in Los Angeles, presented interim results from the ALLSTAR trial (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) at the American Heart Association’s Scientific Sessions held November 11 to 15, 2017, in Anaheim, CA. Thomas J. Povsic, MD, of Duke was a principal investigator for ALLSTAR.

Preclinical studies have shown that allogeneic CDCs are equivalent to autologous CDCs. CAP-1002 is an allogeneic CDC that has been discussed in more than 100 peer-reviewed manuscripts. Phase 2 of ALLSTAR (N = 142) enrolled patients with an MI in the previous 12 months and percutaneous coronary intervention (PCI); other inclusion criteria included infarct of at least 15% of the mass of the left ventricle (LV) and LV ejection fraction (LVEF) of less than 45%.

Patients were randomized to CAP-1002 (n = 95) or placebo (n = 47); 5 individuals in the CAP-1002 group and 3 patients in the control group did not receive treatment. The primary cohort included patients who were matched for donor-specific antibodies (DSA). Individuals randomized in an exploratory cohort were not matched for DSA.

The primary efficacy endpoint was change in infarct size at 12 months compared with baseline. Secondary efficacy endpoints included change in LV structure and function, as well as cardiac biomarkers, at 6 and 12 months. The trial protocol allowed for an interim analysis after all patients had been observed for at least 6 months, which included results from 121 patients in the primary cohort and 13 patients in the exploratory arm.

ALLSTAR did not reach the primary efficacy endpoint. Compared with placebo, CAP-1002 did not significantly reduce infarct size at 6 or 12 months in the primary (matched) cohort. In the exploratory (unmatched) arm, patients treated with CAP-1002 experienced a significant reduction in infarct size compared with placebo at 12 months. There was no significant difference between CAP-1002 and placebo in the unmatched cohort at 6 months.

Compared with placebo, CAP-1002 was not associated with significant differences in LV end-diastolic volume (LVEDV) or LV end-systolic volume (LVESV) in the primary (matched) cohort. However, in the exploratory (unmatched) cohort, CAP-1002 significantly reduced LVEDV and LVESV at 6 months compared with controls (P = .004 and P = .0005, respectively). CAP-1002 also significantly reduced LVESV, but not LVEDV, at 12 months. Biomarker levels (NT-proBNP) were lower in the matched cohort, which trended toward significance at 6 months but not 12 months. The unmatched cohort did not show significant differences at 6 or 12 months.

No deaths or strokes occurred in patients who received CAP-1002. The major adverse cardiovascular event rate was 7.8% for CAP-1002 versus 11.4% for controls (P = .49). In addition, CAP-1002 was associated with a lower rate of nonfatal MI and hospitalization for heart failure.

Although CAP-1002 did not demonstrate a significant reduction in infarct size compared with placebo, Henry found areas for optimism. For instance, some improvement was noted in LV volumes and biomarker levels. In addition, ALLSTAR demonstrated that the use of evidence-based medicine in the setting of MI can improve patient outcomes: no deaths occurred in ALLSTAR, even though patients had large infarcts and compromised LVEF. However, Henry also mentioned that the influence of matched DSA or unmatched DSA on outcomes requires further study.

Source: Henry TD, Kereiakes DJ, Kowalchuk G, et al. Innovative therapies and novel applications: 6-month results of ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) trial: a randomized, placebo-controlled, double-blind study. Presented at: American Heart Association Scientific Sessions 2017; November 11-15, 2017; Anaheim, CA. Abstract LBS.07.