Stem Cell Transplants Delay Disease Reactivation in Patients with Aggressive Multiple Sclerosis

Patients with relapsing-remitting multiple sclerosis (MS) who are treated with currently available disease-modifying drugs (DMARDs) usually experience disease reactivation within the first five years of treatment follow-up. Many of the available treatments for MS only confer complete control of disease activity in a small percentage of patients.

Recent results from the HALT-MS trial, conducted by the National Institute of Allergy and Infectious Disease (NIAID), a department of the National Institutes of Health (NIH), demonstrate that treatment with high doses of immunosuppressive chemotherapy followed by the transplant of autologous hematopoietic stem cells (HDIT/HCT) effectively resets the immune system. Researchers found that treatment with HDIT/HCT halted disease progression, relapse of symptoms, and the appearance of new brain lesions in 69% of patients with MS. Notably, most HALT-MS trial participants remained in remission five years after only one treatment with HDIT/HCT.

Sustained remission was maintained even in the absence of the use of DMARDs in most patients, and some patients even experienced improvement in mobility and neurologic function. The trial was the five-year follow-up to the three-year report that appeared in JAMA Neurology in December 2014.

These findings could change the standard of care for MS, said NIAID Director Anthony S. Fauci, MD, in a press release. He emphasized treatment with HDIT/HCT “may be substantially more effective than long-term treatment with the best available medications for people with a certain type of MS.”

Discontinuation of treatment with DMARDs is often associated with disease reactivation within a few months. Previous studies have shown that only 37% of the patients who received natalizumab, 14% of those who received interferon beta-1a, and 32% of the patients who received alemtuzumab had no evidence of disease after two years of treatment. In contrast, the HALT-MS event-free survival was estimated to be approximately 83% at two years, approximately 78% at three years, and approximately 69% at five years after a one-time dose of HDIT/HCT.

An unrelated 2016 study looking at treating aggressive MS also featured high doses of chemotherapy coupled with autologous hematopoietic stem-cell transplantation. In this study, which was published in The Lancet, approximately 70% of patients experienced activity-free survival three years after treatment. These patients also experienced no relapses or new brain lesions during this period.

Richard Nash, MD, who is a physician at the Colorado Blood Cancer Institute and lead author of the HALT-MS study, told BioPharm International that both the HALT-MS and The Lancet studies "used high-dose therapy and autologous hematopoietic cell transplantation after CD34 selection” and both trials “had similar results in that about 70% of the patients were without evidence of relapse, further loss of neurological function, or changes on the MRI.”

Mark Freedman, MD, director of the multiple sclerosis research unit at The Ottawa Hospital and lead researcher of The Lancet study, pointed out some key differences between his and Nash's study. Freedman told this publication that there were differences in the intensity of the chemotherapy regimen used in the studies, and the study populations were different. Freedman's study enrolled patients with more agressive disease activity, and researchers completely wiped out the immune systems of their patients in this study. As a result, none of the study participants in Freedman's trial had a single MRI lesion or attack 13 years following treatment. Conversely, the HALT-MS study steadily lost patients to the study's endpoint-which was renewed activity of disease-over time. Freedman said that because the patients' immune systems in the HALT-MS were not completely obliterated by chemotherapy prior to stem-cell transplantation, some of the patients in this trial continued to experience brain atrophy well after six months.

Although FDA has released draft guidance documents for the regulation of human cells, tissues, or cellular or tissue-based products (HCT/Ps), it has not yet finalized the drafts or amended the text to reflect comments from a September 2016 meeting on the guidance documents.

Sources: NIH, JAMA Neurology