Hot topics continued at ECTRIMS 2019 in Stockholm with Joachim Burman (Department of Neurology, Uppsala University Hospital, Sweden), who stepped up to the podium to discuss autologous haematopoietic stem cell transplantation (aHSCT) for multiple sclerosis (MS), embracing the viewpoint that the therapy is indeed ready for prime time.
Diving straight into the evidence base for aHSCT, he showcased data from Sormani et al1 that demonstrated that the proportion of patients with no evidence of disease activity (NEDA-3) was much higher after treatment with aHSCT when compared to “typical” MS drugs or placebo.
Dr Burman went on to discuss ASTIMS, the first trial of aHSCT therapy (plus immunomodulation) randomised 1:1 with mitoxantrone chemotherapy (20 mg every month for six months). Although the study was terminated early due to the slow accrual of patients (as mitoxantrone was beginning to be superseded during the study period), relapsing-remitting (RRMS) or secondary progressive (SPMS) MS patients were included for a significant proportion of the trial. Crucially, ASTIMS uncovered that the evolution of new T2 lesions was much higher in the mitoxantrone group, thereby supporting the concept of aHSCT.
The MIST trial, published this year in JAMA3, randomised aHSCT 1:1 with a control arm of standard disease-modifying therapies (DMTs). Inclusion criteria were an Expanded Disability Status Scale (EDSS) of 2–6, RRMS with ≥ 2 relapses in the previous 12 months, and at least 6 months of failed, approved therapy. Blinding for EDSS score and MRI-scan evaluation was performed, and the study allowed for crossover if the primary endpoint of sustained disability progression was reached.
“There was a huge difference between the DMT arm and the aHSCT arm. By five years, nearly 80% of those in the control arm had progressed in EDSS, whereas in the transplant arm it was about 10%,” said Dr Burman. Secondary endpoints included annualised relapse rate (0.78 for DMT, 0.02 for aHSCT; a 97.5% risk reduction), improvement in quality of life (SD36 score 51 to 71 for aHCST, no change for DMT) and change in EDSS score (3.3 to 4.0 for DMT, 3.4 to 2.4 for aHSCT).
Speaking on the EDSS changes, Dr Burman commented: “This is really something astonishing to me. Most trials show a slowing of disability rather than improvement.” Similarly, NEDA-3 scores were substantially higher in the aHCST arm at around 80% (out to five years) compared to 10% in the control group.
Since its inception, the main concern with aHSCT therapy has been mortality, but safety has definitely improved in recent years, said Dr Burman. Indeed, while collective data indicate that treatment-related mortality (TRM) dropped from 3.6% before 2005 to 0.3% after 2005, in low-intensity regimens, the TRM is zero.
No mortality was seen in the MIST trial, continued Dr Burman, nor was there any development of life-threatening events. The most common adverse events were disturbances in electrolyte concentration, as well as febrile neutropenia, but adverse events were not generally of clinical relevance.
In the follow-up period, there were some increased instances of dermatome varicella zoster (7 vs 2 for control), and minor differences in hyperthyroidism (3 vs 1) and hypothyroidism (1 vs 0).
In his closing remarks, Dr Burman turned to whether aHSCT is cost-effective. “Most of the costs [of] aHSCT are related to in-patient care,” he said. “In most countries in Europe, the cost associated with aHSCT is equivalent to 2–3 years of second-line DMT.”
For more coverage from ECTRIMS 2019, please click here.