Design: Case report

Setting: Outpatient/inpatient

Patients or Participants: 32 yo G0 with new onset, heavy menses

Interventions: 6 months after initiation of belimumab therapy

Measurements and Main Results: An ultrasound done 9 months after initiation showed a fibroid measuring 8.9x6.9x 8.0 cm (ellipsoid volume 2053cm³). At 13 months after initiation, it measured 13.2x9.8x9.1cm (4931cm³; 140% increase in 4 months). During an emergency vaginal myomectomy, a 5.0x3.0x1.0 cm mass and additional 247g of benign leiomyoma was removed. Within 2 months thereafter, at 15 months after initiation of belimumab, the fibroid was even larger, measuring 17.0x8.5x8.8 cm (5326 cm³). This represents an 8% increase in size from the second ultrasound.

Conclusion: As belimumab is a biologic immunosuppressant, this case report suggests an immune-related component of fibroid growth. Belimumab is an antibody that specifically binds the soluble form of B lymphocyte stimulator (BLyS), but it may also have affinity for other receptors and have downstream cell-signaling effects in pathways related to uterine fibroids. For example, both B lymphocytes and endometrial cells are known to utilize estrogen receptors and signaling via IL-6, offering potential mechanisms of interaction. Among other possible pathways, PI3K/AKT-mTOR has been shown in human and rat models to be significantly upregulated in the pathogenesis of uterine fibroids. Theoretically, belimumab may be implicated in fibroid growth if it were to directly activate this pathway or indirectly cause expression of G-protein-coupled-receptor 10 or loss of tumor suppressor NRSF/REST.

Further research regarding belimumab and fibroid cell-signaling pathways must be done. Advances may provide potential immunologic, non-hormonal, and non-surgical treatments that target fibroid growth.