Lenalidomide Demonstrates Safety in Anti-MAG Neuropathy

Amro Stino, MD

Results from a phase 1b study (NCT03701711) evaluating lenalidomide (Revlimid; Bristol Myers Squibb), an FDA-approved cancer treatment, demonstrated that the drug is well tolerated and safe in patients with anti-myelin-associated glycoprotein (MAG) neuropathy, with encouraging preliminary efficacy trends.¹

Among 7 patients (6 men; mean age, 67 years) with anti-MAG titer positivity and distal acquired demyelinating sensorimotor (DADS) treated with 25-mg lenalidomide, no dose-limiting toxicities (DLTs) were observed in the 1-year dose escalation phase. One patient developed pulmonary embolus, but that was expected according to the study authors.

Amro Stino, MD, assistant professor of neurology, University of Michigan Medical School, presented these results at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22. He and his colleagues concluded that the positive preliminary data warrants continued and larger study exploration.

The study aimed to determine the maximum tolerated dose (MTD) and examine the safety profile of lenalidomide, while secondary measures such as Medical Research Council Sum Score (MRCSS) and grip strength evaluated strength. Disability, another secondary measure, was assessed using Inflammatory Neuropathy Cause and Treatment Group (INCAT) score, Rasch-built Overall Disability Scale (RODS), and Scale for Assessment and Rating of Ataxia (SARA).

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Patients included in the study received lenalidomide 10 mg, 15 mg, or 25 mg (days 1-21 of 28-day cycle) and dexamethasone 20 mg (days 1, 8, 15, and 22) following a Bayesian optimal interval design. Overall, 4 patients completed the 9-12 months of enrollment, with 3 patients who showed positive trends across both I-RODS (baseline range, 32-46; post-treatment range, 39-47) and Jamar grip strength (baseline range across both hands, 68-98; post-treatment range, 75-100).

Lenalidomide received its first FDA-approval in 2005 to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality or without additional cytogenetic abnormalities.²

Years later, in 2013, it was approved for the treatment of patients with relapsed or refractory mantle cell lymphoma. The FDA expanded the indication for lenalidomide in 2015 in combination with dexamethasone to include patients newly diagnosed with multiple myeloma. It was further indicated in 2017 for patients with multiple myeloma following autologous hematopoietic stem cell transplant and was approved in combination with rituximab in 2019 for the treatment of adult patients with previously treated follicular lymphoma or marginal zone lymphoma.

A study published in the European Journal of Cancer in 2016 found that the risk of peripheral neuropathy is lower with lenalidomide than thalidomide, another anti-cancer approved treatment. Among 858 new users of lenalidomide, 244 (29%) developed neuropathy during 587 person-days. Compared with thalidomide initiators, lenalidomide initiators had a reduced risk of peripheral neuropathy (hazard risk, 0.71; [95% CI, 0.56-0.92]).³

The anti-inflammatory effects of lenalidomide have been closely observed by clinicians and have even opened the door for new opportunities. Cleveland Clinic recently announced that it will conduct a study assessing the therapeutic potential of the anti-cancer drug in patients with early-stage Alzheimer disease (AD), or mild cognitive impairment.⁴

Lead investigator Marwan Sabbagh, MD, director, Lou Ruvo Center for Brain Health, Cleveland Clinic, recently sat down and provided an overview on how the drug will be evaluated and why it was chosen in a conversation with NeurologyLive. Listen in to his thoughts below.

For more coverage of AAN 2021, click here.

REFERENCES

1. Stino A, Elsheikh b, Kline D, Smith R, Efebera Y. Lenalidomide in Anit-MAG neuropathy: phase 1b study. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P19.060

2. Revlimid FDA approval history. Drugs.com. https://www.drugs.com/history/revlimid.html. Updated April 1, 2021. Accessed April 23, 2021.

3. Luo J, Gagne JJ, Landon J, Avorn J, Kesselheim AS. Comparative effectiveness and safety of thalidomide and lenalidomide in patients with multiple myeloma in the United States of America: a population-based cohort study. Eur J Cancer. Published online November 17, 2016. doi: 10.1016/j.ejca.2016.10.018

4. Cleveland Clinic Lou Ruvo Center for Brain Health receives NIH and ADDF grants, totalling $4.6 million to study FDA-approved cancer drug lenalidomide in Alzheimer disease. News release. Cleveland Clinic. January 27, 2021. Accessed April 23, 2021. https://newsroom.clevelandclinic.org/2021/01/27/cleveland-clinic-lou-ruvo-center-for-brain-health-receives-nih-and-addf-grants-totaling-4-6-million-to-study-fda-approved-cancer-drug-lenalidomide-in-alzheimers-disease/