MultiStem Cell Therapy Not Superior to Placebo in Patients With Ischemic Stroke


Further research is needed to determine if cell therapy may be beneficial to certain subgroups of patients.

Allogeneic MultiStem cell therapy was safe but was not found to improve short-term outcomes in patients with ischemic stroke treated in the phase 2/3 TREASURE trial (NCT02961504).

“Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow–derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke,” first author Kiyohiro Houkin, MD, Hokkaido University, Sapporo, Japan, and colleagues wrote.

The multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) clinical trial was conducted at 44 academic and clinical centers across Japan between November 15, 2017, and March 29, 2022. Patients were at least 20 yeras of age with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) score of 8-20 at baseline, confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset.

"In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study,” Houkin and colleagues wrote.

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The primary end points were safety and excellent outcome at day 90, measured as a composite of a mRS score of 1 or less, NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Investigators performed data analysis between May 9 and August 15, 2022. Patients were randomized to receive 1.2 billion cells intravenous MultiStem or intravenous placebo within 18 to 36 hours of ischemic stroke onset.

The study included 206 patients, 104 that received MultiStem and 102 that received placebo, with a mean age of 76.5 (range, 35-95) years. More than half of patients were men (n = 112; 54.4%) and there were no between-group differences in primary and secondary end points. The rate of patients achieving excellent outcomes at day 90 did not differ significantly between the MultiStem (n = 12; 11.5%) and placebo groups (n = 10; 9.8%; P = .90; adjusted risk difference, 0.5% [95% CI, −7.3% to 8.3%]). The rate of adverse events was similar between treatment groups.

Investigators did find that patients with an ischemic core volume of 50 mL or less had significantly better outcomes in the MultiStem (n = 8; 29.6%) vs placebo groups (n = 3; 8.1%; P = .04; adjusted risk difference, 20.4% [95% CI, 1.0% to 39.9%]). They also saw a benefit in patients aged 64 years or younger in the MultiStem (n = 8; 80%) vs placebo groups (n = 5; 41.7%;P = .08; adjusted risk difference, 37.2% [95% CI, −0.4% to 74.8%]).

"Efficacy was suggested in patients with large infarcts and possibly in younger patients based on exploratory subgroup analyses with no correction for multiple comparisons. A combined analysis of the TREASURE and ongoing MASTERS-2 trials will be conducted to confirm the efficacy and safety of MultiStem therapy,” Houkin and coauthors concluded.

Houkin K, Osanai T, Uchiyama S, et al. Allogeneic Stem Cell Therapy for Acute Ischemic Stroke The Phase 2/3 TREASURE Randomized Clinical Trial. JAMA Neurol. Published online January 16, 2024. doi:10.1001/jamaneurol.2023.5200
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