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

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.

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.