From Brain to Bone Marrow: Concurrent Use of Bruton’s Tyrosine Kinase Inhibition and Anti-CD20 Therapy in Relapsing Multiple Sclerosis With Chronic Lymphocytic Leukemia
Shama Patel1, Michelle Maynard2, Umang Gautam3, Sam Hooshmand1
1Neurology, Medical College of Wisconsin, 2Neurosciences, Froedtert Neurosciences Clinic, 3Hematology & Oncology, Aurora Baycare Medical Center
Objective:

To describe the management of relapsing multiple sclerosis (RMS) with coexisting chronic lymphocytic leukemia (CLL) using concurrent B-cell–directed therapies with complementary mechanisms of action

Background:

RMS and CLL are distinct B-cell–driven disorders that rarely coexist but share pathogenic features, including antigen presentation to T-cells and secretion of pro-inflammatory cytokines. Optimal treatment strategies for patients with both conditions remain undefined, and to date, no published reports describe the simultaneous treatment of RMS and CLL. We present a case of a patient previously stable on natalizumab, an immune-trafficking agent that increases peripheral lymphocyte counts, who was transitioned to combined therapy with the Bruton’s tyrosine kinase inhibitor (BTKi) acalabrutinib and the anti-CD20 monoclonal antibody ofatumumab.

Design/Methods:
Not applicable
Results:
A 47-year-old man with RMS remained stable on natalizumab for several years before developing CLL. Natalizumab was maintained until CLL progression with associated dermatologic symptoms prompted transition to acalabrutinib plus subcutaneous ofatumumab. The transition was well tolerated, with an intentional overlap of immunotherapy: acalabrutinib was initiated one week before the final natalizumab infusion, and ofatumumab was started one week after. Nearly one year later, the patient’s MS is clinically and radiographically stable. Laboratory testing showed a marked reduction in lymphocyte counts, from 105.8 K/mcL to 7.74 K/mcL. We anticipate transitioning to BTKi monotherapy for management of both conditions.
Conclusions:

This case underscores the therapeutic complexity of managing concurrent RMS and CLL. It suggests that B-cell–directed therapies, BTKi and anti-CD20, can be used in combination. A crucial consideration is the need to overlap immunotherapies when transitioning from an immune-trafficking agent in the setting of high lymphocyte counts, to reduce the risk of rebound disease. Multidisciplinary, individualized care is essential, and further research is needed to establish safety, define optimal dosing, and explore BTKi as a therapeutic bridge between autoimmune and oncologic disease.

10.1212/WNL.0000000000213017
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