Multiple myeloma is a plasma cell malignancy that mainly affects the bones and skeletal system. The involvement of the brain as a site is very rare; it usually takes place via calvarial lesions with intracranial extension and is considered resistant to treatment. This report presents the case of a patient presenting with refractory MM and discusses in detail the efficiency of bendamustine-pomalidomide therapy and daratumumab-based maintenance after ASCT.

A 62-year-old female was diagnosed with kappa-positive MM in 2015, when plasma cell infiltration in the bone marrow was 20%. The patient underwent chemotherapy followed by ASCT in 2016. This patient attained remission after the transplant. Three years later, she presented with brain involvement, and MRI confirmed lesions of the parietal calvarium along with soft tissue expansion into the brain.

The patient received radiotherapy to the affected area of the brain and initiated bendamustine-pomalidomide therapy; indeed, remarkable improvements were made in lesions of the brain and skeleton. Following that response, daratumumab, lenalidomide, and dexamethasone maintenance therapy was initiated to ensure ongoing disease control. Currently, the patient is clinically stable, with no evidence of further progression on follow-up imaging.

This case underlines the rarity of brain involvement in MM, as well as the role of ASCT as part of first-line treatment. The late appearance of extramedullary brain involvement three years post-transplantation truly epitomizes the whim of MM. Bendamustine-pomalidomide therapy was effective for refractory disease management, whereas daratumumab-based maintenance has helped maintain stability.