NATIONAL HARBOR, Md. -- Alemtuzumab (Lemtrada) appeared to stabilize or improve disability in multiple sclerosis over 5 years, researchers reported here.
In an analysis of data from both the initial and extension phase of the CARE-MS II trial, the mean change in Expanded Disability Status Scale (EDSS) over that time was only +0.06, , of North Central Neurology Associates in Cullman, Ala., and colleagues reported at the Consortium of Multiple Sclerosis Centers (CMSC) annual meeting.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"We have debates over whether a 0.5-point change on the EDSS is clinically meaningful, so this is really impressive," , of Ohio Health in Columbus, who was a co-author on the study, told 乌鸦传媒.
Most of these patients (60%) only received the standard two courses of alemtuzumab -- an initial 5-day infusion, followed by a 3-day infusion a year later -- and didn't require additional infusions, LaGanke reported.
Alemtuzumab is an anti-CD52 monoclonal antibody that targets T and B cells, but spares lymphocyte precursors. The latter is thought to be the mechanism that could account for its sustained effects, as it effectively "reboots" the immune system, changing it from a pro-inflammatory to an anti-inflammatory state, LaGanke said.
It was originally approved in 2001, with a brand name of Campath, for the treatment of B-cell chronic lymphocytic leukemia, and is sometimes used off-label as an immunosuppressive agent in kidney transplant. It is a powerful treatment and is .
Its indication in MS was approved in 2014 on the basis of data from the CARE-MS I and CARE-MS II trials.
In this analysis of long-term follow-up from the CARE-MS II trial, LaGanke's group studied the 393 patients who enrolled in the extension phase after the first 2-year randomized, controlled phase of the trial was complete.
Most of the patients (91%) remained in the study at the end of the 5-year period, which was technically 4 years after the final dose.
In addition to the majority of patients not needing additional alemtuzumab dosing, only 7.6% of patients went on another disease-modifying therapy over the course of the trial.
A third of patients achieved 12-month confirmed disability improvement (CDI) -- defined as at least a 1-point decrease in EDSS scores -- along with 43% who had 6-month CDI and 48% who had 3-month CDI, LaGanke reported.
About 77% of patients had either improved (25%) or stable (52%) EDSS scores at the end of year 5, he added. Similar proportions were seen across specific functional outcomes, including cerebellar, pyramidal, sensory, cerebral, bowel/bladder, brainstem, and visual scores.
LaGanke did not report adverse event data, but Boster told 乌鸦传媒 that rates of adverse events at 5 years looked similar to those seen at the end of the randomized controlled portion of the trial. Overall, across studies, the rate of thyroid cancer was 0.3%, melanoma was also 0.3%, and lymphoma rate was 0.2%, he said.
Clinicians are aware of the other side effects of the drug, including thyroid disease and the potential for opportunistic infections, said , of Loyola Medicine in Maywood, Ill.
At the ECTRIMS meeting in 2015, , of Charles University in Prague, reported adverse event rates from both CARE-MS trials, with the incidence of thyroid autoimmune events peaking at 20% in the first year of the extension (treatment year 3) and declining thereafter.
Immune thrombocytopenia, another worrisome side effect, was relatively rare at 1.1% during the entire 5-year study, according to Havrdova's report.
Infections, however, were common and remained so during the extension. Some 56% of alemtuzumab-treated patients developed infections during the main study's first year; in year 5, 40% developed infections, her group found.
"We have to couch this tremendous optimism and very minimal side effects early on with what are the potentials risks later on," Perrin-Ross, the co-chair of the CMSC's scientific program committee, told 乌鸦传媒.
"We've seen alemtuzumab do wonders, but those of us who been around long enough also realize we have to be ever vigilant" for adverse events down the line, particularly regarding thyroid disorders in relatively young patients, she said.
It is highly recommended that patients be placed on anti-viral therapy when taking alemtuzumab, and eventually weaned off, she added.
LaGanke concluded that alemtuzumab "may provide a unique treatment approach with durable efficacy" for patients with relapsing-remitting MS who have failed other therapies.
Disclosures
The study was supported by Genzyme and Bayer.
LaGanke disclosed relevant relationships with Genzyme, Acorda, Bayer, Biogen, Cephalon, EMD Serono, Novartis, Pfizer, Questcor, Strativa, Teva, and UCB. Co-authors disclosed relevant relationships with Genzyme, Biogen, Novartis, Teva, Genzyme, Medtronic, Mallinckrodt, Abbvie, Acorda, Avanir, Bayer, Osmotica, Questcor, Roche, Synthon, Teva, Sanofi, Merck Serono, Actelion, and Receptos.
Primary Source
Consortium of Multiple Sclerosis Centers
LaGanke C, et al "Patients with active relapsing-remitting MS and inadequate response to therapy at baseline show durable disability improvement over 5 years with alemtuzumab: CARE-MS II" CMSC Meeting 2016; Abstract DX02.