Sharp lymphocyte drop seen quickly in SPMS patients on Mayzent

Some people with secondary progressive multiple sclerosis (SPMS) using Mayzent (siponimod) show a severe drop in their number of lymphocytes, a condition known as lymphopenia, shortly after starting treatment, a report on its real-world use in the U.K. found.

Lymphocytes are white blood cells that help the immune system protect against infections.

The development of severe lymphopenia, however, did not associate with patients’ lymphocyte levels before treatment (a baseline measure), initial Mayzent maintenance dose, their age or sex, or the use of other disease-modifying MS therapies also linked to lymphopenia.

“The lack of a clinically significant association for baseline lymphocyte count will likely surprise clinicians and may provide confidence in prescribing for [people with SPMS] with lower baseline counts. The lack of association for sex is similarly encouraging,” the researchers wrote.

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The report, “Real-world data on siponimod-related lymphopenia among people with secondary progressive multiple sclerosis,” was published in the Multiple Sclerosis Journal.

MS is caused by the immune system mistakenly attacking the myelin sheath, a protective coating around nerve fibers that helps them send electric signals efficiently. With SPMS, disease symptoms gradually worsen over time, including in the absence of new relapses.

Mayzent is an approved oral therapy for relapsing MS patients, including those with active SPMS, to reduce the frequency of relapses and delay disability progression.

It works by modulating the sphingosine 1-phosphate (S1P) receptors at the surface of some immune cells, trapping them inside lymph nodes to prevent them from getting into the brain or spinal cord and cause inflammation. Lymph nodes are organs where immune cells mature and are stored.

As Mayzent reduces the number of circulating lymphocytes, or immune cells, its use has been linked with a higher risk of infections. People with SPMS who develop grade 4, or severe lymphopenia (lymphocyte levels lower than 0.20×10⁹/L), are advised to lower their Mayzent dose or, if already on a low dose, to interrupt treatment. Of note, the range of a normal lymphocyte count for adults is 1 to 4.8 × 10⁹/L.

However, “it is unknown which people with [SPMS] are more likely develop grade 4 lymphopenia,” the researchers wrote. Potential risk factors include age, sex, number of lymphocytes when starting treatment, and recent use of a disease-modifying treatment like fingolimod (sold as Gilenya), an S1P modulator also associated with lymphopenia.

Scientists with three MS centers analyzed data covering 188 SPMS patients treated with Mayzent to determine the frequency and degree of lymphopenia, and characteristics that might relate to developing grade 4 lymphopenia.

Grade 4 lymphopenia in 8.5% of study patients after 1 month of treatment

Results showed that 8.5% of patients (15 of 176 people) experienced grade 4 lymphopenia one month after starting on Mayzent, 5.9% after six months of its use (seven of 118 people), and 4.7% (four of 87 people) at one year of use.

At all time points, most patients had grade 3 lymphopenia, meaning lymphocyte blood levels between 0.20 and 0.49×10⁹/L.

Severe lymphopenia tended to start early, at a mean of 64 days (about two months) after beginning with Mayzent, the researchers noted, but a first appearance also was seen as late as 7.3 months into the therapy’s use.

“This retrospective cohort study demonstrates that lymphopenia develops quickly after starting [Mayzent], occurs to a significant extent, and is present throughout 12 months of data collection,” they wrote.

No clinically significant associations existed for patient characteristics and a grade 4 lymphopenia within six months of starting treatment, including age, sex, prior DMT use, or initial Mayzent maintenance dose (2 mg or 1 mg).

“It is important for MS clinicians to be aware that the development of grade 4 lymphopenia within 6 months of commencing [Mayzent] lacks clinically significant associations with baseline lymphocyte count, age, dosage, sex, or [previous use of DMT associated with lymphopenia]: these factors should not unduly influence treatment decisions,” the scientists concluded.

A noted study limitation was in not being able to report on infections that may have developed in these patients.