The BCL2 Inhibitor Venetoclax Plus Rituximab Is Active in MYD88 Wild-Type Polyneuropathy With Anti-MAG Antibodies

Objectives: Ibrutinib is active in anti-myelin-associated glycoprotein (MAG) polyneuropathy with MYD88L265P mutation; however, its efficacy is likely to be low in MYD88 wild-type patients. Venetoclax, an oral inhibitor of BCL2, in combination with rituximab is highly active in ibrutinib-resistant hematologic malignancies. We report on the first patient with anti-MAG polyneuropathy and MYD88 wild-type who responded to venetoclax-rituximab. Methods: A 62-year-old woman with chronic lymphocytic leukemia had IgM/K anti-MAG neuropathy. She needed bilateral support to walk outdoors, despite therapy with rituximab/cyclophosphamide. Tremor and symptoms at arms prevented her capability of performing common tasks. Bone marrow genetic showed lack of MYD88 mutation. Venetoclax was given orally starting from 20 mg up to 400 mg for 24 months. Rituximab was administrated IV, after the ramp-up phase, at 375 mg/m2 for the second month and then monthly at 500 mg/m2 for months 3-7. Results: After 12 months of venetoclax IgM levels decreased from 1.16 to 0.52 g/L, the paraproteins became undetectable and anti-MAG antibody titer decreased. The patient regained the capability of walking independently. Tremor disappeared, she is back able to write and knitt. Discussion: The first patient with anti-MAG neuropathy treated with venetoclax-rituximab shows encouraging results. Classification of evidence: This study provides Class IV evidence that for a patient with relapsed anti-MAG antibody polyneuropathy, MYD88 wild-type, venetoclax plus rituximab is effective.