Pseudoprogression of extramedullary lesions during elranatamab therapy in relapsed or refractory multiple myeloma

Pseudoprogression comprises a transient increase in tumor burden caused by immune cell infiltration or inflammatory responses after immunotherapy, including chimeric antigen receptor T-cell therapy and the use of bispecific antibodies. Although pseudoprogression has been reported following several immunotherapy types, cases of pseudoprogression associated with elranatamab remain rare. Herein, we describe the case of a 67-year-old woman with relapsed/refractory multiple myeloma who developed pseudoprogression of extramedullary lesions following treatment with elranatamab. On day 4 of therapy, the patient presented with left periorbital swelling and lagophthalmos. Computed tomography (CT) revealed the enlargement of multiple extramedullary lesions in this patient. Dexamethasone administration improved the ocular symptoms. Lagophthalmos recurred after administration of the second dose of elranatamab but responded to dexamethasone. On day 13, a CT-guided biopsy of the chest wall lesion revealed dense T cell infiltration within the tumor tissue, consistent with pseudoprogression rather than true progression. The patient's serum M-protein levels decreased within 2 weeks of treatment initiation. At 2 months, follow-up CT demonstrated a reduction in the extramedullary lesions, and the patient achieved a very good partial response. This case highlights that pseudoprogression may occur during elranatamab therapy, similar to that which may occur with other T-cell-redirecting immunotherapies. Differentiating pseudoprogression from true progression is clinically important, as misinterpretation may lead to premature discontinuation of effective therapy. Careful clinical evaluation, integration of imaging findings, and histopathological confirmation (whenever feasible) are essential for the appropriate management of such cases.