HALT-MS: Five Year Study Results

Research Summary: High dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

The 5 year results of the HALT-MS trial were today published in Neurology.  The HALT-MS clinical trial has been aiming to assess the impacts of high-dose immunosuppressive therapy (HDIT), followed by autologous haematopoietic cell transplantation (HCT) in people with relapsing-remitting MS (RRMS).  It is a multicenter trial that encompasses hospitals throughout the US, Canada and the UK.  The study involved 24 participants that had all been diagnosed with RRMS for less than 15 years and had an EDSS of 3.0-5.5.  All of the people involved in the study had previously failed other disease-modifying therapies.

At the 5 year time point, the rate of success was reported as 69.2%.  This outcome was measured in terms of “event free survival” (EFS), which was defined as survival without death or disease activity (disability progression, relapses or new lesions on MRI).  When this was further analysed, it was seen that higher percentages occurred in each individual category:  no progression (91.3%), no clinical relapses (86.9%) and no MRI activity (86.3%).  Importantly, even for those that did not maintain EFS for the 5 years, the number of relapses that they experienced after the transplant was lower than beforehand.

Comparing this to previous studies, the authors report that the levels of NEDA (no evidence of disease activity) after 2-3 years are much lower for glatiramer acetate/Copaxone (19%), interferon-beta-1a (21%), natalizumab/Tysabri (37%) and alemtuzumab/Lemtrada (39%).  It should be noted that differences in the study cohorts may have contributed to this as well.

The primary safety concerns associated with the study were reported in the earlier paper describing the results at the 3 year time point.  These adverse events were primarily those to be expected with the treatment, such as infections and reductions in the number of blood cells.  Between 3 years and 5 years, the total number and the severity of the adverse events decreased.  Three people in the study did not respond to treatment and had significant worsening of disease and ended up dying.  The deaths occurred 2.5 years, 3.5 years and 4.5 years after receiving the transplant.  The authors reported that none of the deaths were attributed to the transplant procedure.

This study provides further evidence to the potential long-term benefits of high-dose immunosuppression and autologous transplantation.  Whilst the procedure still represents a major undertaking, this trial (combined with others around the world) shows that adverse effects are being managed effectively and mortality rates are being kept low.

The authors conclude that HDIT/HCT is a reasonable consideration for people with relapsing-remitting MS that fail first-line treatments, such as those included in this trial.  Although with other evidence that suggests that this treatment is more effective the earlier it is undertaken, should it be presented as an initial treatment option as long as the risks are fully explained?  The answer to this remains unclear, and it seems unlikely to occur in the short-term, but it will be interesting to see how it develops over the coming years.

The abstract for this study can be reviewed in full here.