Allogeneic Stem Cell Therapy Falls Short on Stroke Outcomes

Bone marrow-derived allogeneic stem cell therapy shortly after ischemic stroke did not improve outcomes at 90 days, a phase II/III randomized clinical trial known as TREASURE found.

The rate of excellent outcomes — a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score (BI) of 95 or greater — did not differ significantly between treatment and placebo groups (11.5% vs 9.8%, P=0.90; adjusted risk difference 0.5%, 95% CI -7.3% to 8.3%), Toshiya Osanai, MD, of Hokkaido University in Sapporo, Japan, and colleagues reported in JAMA Neurology.

However, exploratory subgroup analyses in patients with mRS scores of 0-2 at day 90 who were treated with the investigational multipotent adult progenitor cell therapy (MultiStem) seemed to show better outcomes, especially for patients with ischemic core volumes of 50 mL or more, and those age 64 or younger.

“Although there were no significant differences in the primary endpoint (excellent outcome at 90 days), subgroup analysis suggested that it may be effective in certain patient groups, such as younger patients and those with larger infarct size,” Osanai wrote in an email to MedPage Today.

Exploratory post hoc analyses also indicated proportions of patients with global stroke recovery and a BI of 95 or greater at day 365 were significantly higher in the cell therapy group. BI scores range from 0 to 100, with a score of 100 indicating total independence.

“We had thought that the main mechanism of cell therapy for acute stroke would be immunomodulating and would start working quickly,” Osanai said. “On the other hand, contrary to expectations, the cell therapy group tended to show predominant symptom improvement at 365 days rather than 90 days. At present, we cannot clearly explain this mechanism.”

Reperfusion therapies for stroke offer varied outcomes, with many patients receiving endovascular thrombectomy still experiencing disability 3 months after stroke. Cell therapy, an alternative of interest, has shown mixed results for other cardiovascular indications. And though some research has suggested improved outcomes for stroke with autologous cell therapy, these studies were limited by small sample sizes and time-consuming procedures for stem cell preparation and administration, Osanai and colleagues noted.

Researchers included 206 adults from academic and clinical centers in Japan who had acute ischemic stroke (baseline NIHSS score of 8-20), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis, and an mRS score of 0 or 1 before stroke onset. Patients with lacunar or brainstem infarction, a change in NIHSS score of 4 or greater during a minimum period of 6 hours between screening and randomization, and those who received combined reperfusion therapy were excluded.

Participants had a mean age of 76.5 and 54.4% were male. They received a single intravenous dose of allogeneic stem cell therapy or placebo for 30-60 minutes between 18 and 36 hours after stroke onset. Patient visits were scheduled at 7, 30, 90, and 365 days after randomization, with phone calls at day 60 and every 2 months after day 90.

Primary safety endpoints, including grade 3 or 4 infusion-related allergic reactions, did not differ between groups. Treatment-emergent adverse events occurred in 29.8% of the cell therapy group and 11.8% of the placebo group.

Limitations of the trial included patient heterogeneity. The authors acknowledged that subgroup and post hoc analyses did not include statistical multiplicity and results were exploratory with small sample sizes. In addition, patients treated with both tissue plasminogen activator and mechanical thrombectomy were excluded.

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