Stem Cell Transplants May Halt MS Progression

Megan Brooks

December 30, 2014

High-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplant (HCT) can induce sustained remission in patients with relapsing-remitting multiple sclerosis (RRMS), according to interim results of the ongoing HALT-MS clinical trial.

Three years after HDIT/HCT, most patients had no loss of neurologic function, clinical relapse, or new brain lesions on MRI. Few serious early complications or late unexpected adverse events occurred, the researchers say.

Richard A. Nash, MD, from the Colorado Blood Cancer Institute in Denver, and colleagues report the interim results in JAMA Neurology online December 29.

"These promising results support the need for future studies to further evaluate the benefits and risks of HDIT/HCT and directly compare this treatment strategy to current MS therapies," said Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases (NIAID), which is funding the HALT-MS trial, said in a statement.

"If the findings from this study are confirmed, HDIT/HCT may become a potential therapeutic option for people with this often-debilitating disease, particularly those who have not been helped by standard treatments," Dr Fauci said.

Potential Therapeutic Option

Autologous HCT has been studied in MS for more than 20 years. Early clinical trials of HDIT/HCT involved patients with advanced disabilities and progressive forms of MS, Dr Nash and colleagues note in their article.

The HALT-MS trial is an ongoing, multicenter, single-group phase 2 study of HDIT/HCT testing whether control of inflammation earlier in RRMS may lead to prolonged remission and potentially reverse neurologic dysfunction.

At baseline, the 24 study patients had an Expanded Disability Status Scale (EDSS) score of 3.0 to 5.5, disease duration less than 15 years, and clinical relapse with loss of neurologic function while receiving disease-modifying therapies in the 18 months before enrollment.

Autologous peripheral blood stem cells were mobilized, collected, CD34 selected, and cryopreserved. Before autologous HCT, patients received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin.

The primary end point, event-free survival, was defined as survival without death or disease activity from confirmed loss of neurologic function, clinical relapse, or new lesions on MRI.

The estimated event-free survival probability was 78.4% (90% confidence interval [CI], 60.1% - 89.0%) at 3 years, 68.6% (90% CI, 44.9% - 83.7%) at 4 years, and 58.8% (90% CI, 33.7% - 77.2%) at 5 years.

At 3 years, EDSS progression-free survival was 90.9% (90% CI, 73.7% - 97.1%) and clinical relapse-free survival was 86.3% (90% CI, 68.1% - 94.5%).

The researchers say final survival probabilities using all 4- and 5-year data will be reported in a future article.

At 3 years, the EDSS score had improved, with a median change of –0.50 (P = .007), the MS Functional Composite score had improved by a median of 0.15 points, and the 29-item MS Impact Scale quality-of-life score had improved by a median of –15.0 points.

"Notably, participants did not receive any MS drugs after transplant, yet most remained in remission after 3 years," Daniel Rotrosen, MD, director of NIAID's Division of Allergy, Immunology and Transplantation, said in a statement. "In contrast, other studies have shown that the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects."

Jury Still Out

There were 130 grade 3 and 94 grade 4 toxic events. The researchers say adverse events were "consistent" with expected toxic effects of HDIT/HCT, and no acute treatment-related neurologic adverse events occurred. Most early toxic effects were hematologic and gastrointestinal and were "expected and reversible," they say.

The coauthors of a linked editorial say this study and another phase 2 single-group study "leave little doubt that high-dose immunotherapy is able to substantially suppress inflammatory disease activity in patients with MS who have active disease in the short term. There is some evidence for long-term suppression of MS."

"Lessons have been learned about how treatment-related morbidity and mortality may be reduced," write M. Mateo Paz Soldán, MD, PhD, from University of Utah, Salt Lake City, and Brian G. Weinshenker, MD, from Mayo Clinic, Rochester, Minnesota.

However, HCT is not a cure for all patients, and the long-term benefits of treatment are still "poorly characterized," they note. And while the death rate associated with HCT is low, "any deaths attributable to treatment are difficult to accept in MS considering the variability in natural history and its low mortality rate."

"The jury is still out regarding the appropriateness and indications of HCT for MS," the editorialists conclude.

The HALT-MS trial is funded by the NIAID, part of the National Institutes of Health, and conducted by the NIAID-funded Immune Tolerance Network. A complete list of author disclosures is listed with the original article.

JAMA Neurol. Published online December 29, 2014. Abstract Editorial

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