Triple-Positive Antiphospholipid Antibody Syndrome in IgG Multiple Myeloma: Complete Serologic Resolution After One Cycle of VRD
Paraneoplastic antiphospholipid syndrome (APS) is a rare autoimmune complication of multiple myeloma (MM) in which the malignant plasma cell clone may produce clinically relevant autoantibodies. The temporal relationship between clonal disease control and serologic resolution remains poorly characterized, with evidence limited to isolated case reports.
Materials and Methods/Case Presentation/Objective:
A 76-year-old woman presented with isolated thrombocytopenia (69 ×10³/µL) without prior thrombotic events. Workup revealed an IgG paraprotein of 2060.48 mg/dL, confirming IgG MM (ISS stage I). Bone marrow immunophenotyping demonstrated a clonal plasma cell population expressing CD45dim, CD19, CD138, CD56, CD38, and HLA-DR - a phenotype found in fewer than 5% of MM cases, potentially reflecting a less differentiated state. Triple-positive antiphospholipid antibodies were identified: anticardiolipin (22.12.25 aCL; IgG 15.7 IgM 418.5; 12.02.26 IgG 14.5 IgM 447.9), anti-beta-2-glycoprotein-I (aβ2GPI; 22.12.25 IgM 269.6; 12.02.26 IgG 38.4), and lupus anticoagulant (LA; positive). ANA was obtained to exclude primary autoimmune thrombocytopenia, returning positive at 1:640; systemic lupus erythematosus was subsequently ruled out by clinical and serologic criteria. Given the high thrombotic risk of triple-positive APS, prophylactic anticoagulation was initiated with acenocoumarol prior to MM diagnosis and transitioned to rivaroxaban following MM confirmation. VRD (weekly bortezomib, 28-day cycles) was then initiated.
Results/Description/Main Outcome Measure(s):
Serologic testing performed 42 days after treatment initiation, prior to cycle 2, demonstrated complete serologic remission: aCL (13.05.26 IgG 8.55 and IgM 13.5), aβ2GPI (13.05.26 IgG 22.1 IgM 18.4), LA (positive to negative), and ANA (1:640 to negative). Complete normalization of triple-positive APS serology after a single cycle of anti-myeloma therapy has rarely been reported. After two cycles, IgG paraprotein decreased from 2060.48 to 1006.13 mg/dL, representing a 51% reduction. Despite complete serologic remission, thrombocytopenia persisted, with platelet counts declining from 69 to 47 ×10³/µL at last follow-up, suggesting dissociation between autoantibody clearance and platelet dynamics, potentially attributable to treatment-related myelosuppression or marrow infiltration.
Conclusion(s).: This case demonstrates complete serologic remission of triple-positive APS after one cycle of VRD in IgG MM presenting with isolated thrombocytopenia and no prior thrombotic events. The concurrent reduction in paraprotein levels and disappearance of all antiphospholipid antibodies strongly support clonal involvement in autoantibody production. The CD19+/HLA-DR+ immunophenotype may reflect a less differentiated plasma cell phenotype with enhanced capacity for aberrant autoantibody production, warranting further investigation. Persistent thrombocytopenia despite serologic remission highlights mechanisms beyond antiphospholipid activity, including myelosuppression and marrow-related factors. This case contributes to the limited literature on monoclonal autoimmune gammopathies and underscores the value of early clonal-directed therapy in atypical autoimmune presentations of MM.
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