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MOBILE: Cell therapy may improve outcomes in patients with CLI
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LAS VEGAS — Autologous bone marrow-derived progenitor cell therapy did not significantly improve rates of amputation-free survival in patients with critical limb ischemia, according to data presented at VIVA 16.
When patients with both diabetes and tissue loss were excluded from the analysis, there was a significant improvement in amputation-free survival, which may spark further study, Michael P. Murphy, MD, associate professor of surgery, associate professor of cellular and integrative physiology – clinical, director of the Vascular and Cardiac Center for Adult Stem Cell Therapy and director of the IU Center for Aortic Disease, Indiana University, Indianapolis, said during a presentation.
MOBILE is the first phase 3 trial of cell therapy for critical limb ischemia (CLI) in the United States. Murphy and colleagues randomly assigned 152 patients with Rutherford class 4 or 5 CLI (mean age, 65 years; 60% men) ineligible for surgical or endovascular revascularization to receive bone marrow-derived progenitor cell therapy (n = 119) or a placebo-controlled sham procedure (n = 36).
“We used concentrated bone-marrow aspirate from the patient’s own bone marrow in patients with [CLI] to prevent amputation,” Murphy said during a press conference. “The aspirate was injected into the leg with severe disease at 40 sites, beginning at the level of the knee, down to the foot itself.”
Randomization was performed on a 3:1 basis because the researchers believed it would be unethical to have a larger control arm in case the therapy worked, Murphy said.
The primary outcome was amputation-free survival at 52 weeks. Patients will be followed for 5 years, Murphy said.
Patients in the cell-therapy group were more likely to achieve the primary outcome compared with those in the placebo group (HR = 0.64; 95% CI, 0.31-1.31).
“There was a strong trend that the treatment of concentrated bone-marrow aspirate improved amputation-free survival vs. placebo, but this did not reach statistical significance,” Murphy said. “The reason for that was that we powered our study anticipating about 40% of the patients in the placebo group would die or have a major amputation.” Instead, the event rate was 30.56% in the placebo group and 20.17% in the intervention group, he said.
However, when a pre-specified subset of patients with Rutherford class 4 (rest pain) with and without diabetes and Rutherford class 5 (tissue loss) without diabetes were analyzed collectively, amputation-free survival rates were significantly higher in the treatment group (treatment group, 86.17%; placebo group, 66.67%; P = .018). Patients with diabetes and Rutherford 5 demonstrated no benefit from bone marrow cell therapy, Murphy said.
To show a statistically significant difference across all subsets of patients would likely require 1:1 randomization of approximately 200 patients, he said.
There was no difference between the groups in adverse events (P = .55) or serious adverse events (P = .329), although the treatment group had “a lower red blood cell count, which we attributed to the bone-marrow aspiration itself, but none of the patients who had anemia had any sequelae related,” Murphy said.
Four patients in the placebo group and five in the intervention group died during follow-up through June (P = .214). Rates of major amputation at 52 weeks were 22.22% in the placebo group and 15.97% in the intervention group.
“We are now moving forward with a continued-access study trying to define the mechanisms of action of this bone-marrow cell preparation in improving amputation, and how we can potentiate that, especially in patients with diabetes and tissue loss,” Murphy said. – by Erik Swain
Reference:
Murphy MP, et al. Late-Breaking Clinical Trials. Presented at: VIVA 16; Sept. 18-22, 2016; Las Vegas.
Disclosure: Murphy reports no relevant financial disclosures.
Perspective
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Michael R. Jaff, DO, FSCAI
I keep hoping that a cell therapy or gene therapy trials will work, and every time I wait with baited breath, I am disappointed. I understand that the researchers potentially found a signal in a subgroup analysis. But the truth of the matter is, Rutherford class 5 patients with diabetes are the patients who present with the worst clinical manifestations of their disease. It’s hard for me to justify excluding them to find a silver lining in the data.
I think we are picking the wrong patient populations for these trials. We should be looking for ways to speed up wound healing after successful revascularization. Patients would love that. Currently, sometimes the procedure restores blood flow but it takes many months for the wound to heal. If there were a therapy to speed that up, it would be hugely impactful. The researchers suggested they will look at that.
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