Precision medicine in hemato-oncology - treatment of refractory multiple myeloma with massive extramedullary...

Multiple myeloma (MM) with extramedullary disease (EMD) represents a subgroup with particularly poor prognosis. The application of precision medicine principles, especially targeted therapy based on the tumor's molecular profile, is a potentially effective treatment strategy.

We present a case of a patient with relapsed/refractory MM and extensive EMD in whom a BRAFV600E mutation was identified using next-generation sequencing. Based on these results, combined treatment with BRAF (enkorafenib) and MEK (binimetinib) inhibitors was initiated, resulting in early regression of tumor lesions and a biochemical response. The therapy was well tolerated despite the patient's advanced disease and comorbidities. After several months, a new plasmacytoma lesion developed that no longer responded to treatment.

Molecular analysis of the resistant lesion revealed biallelic inactivation of the TP53 tumor suppressor gene, which was not present in the original lesions. This alteration likely represents a mechanism of acquired resistance. The dynamics of the BRAFV600E mutation were also monitored in plasma using cfDNA and digital PCR.

This case illustrates the potential of precision therapy in the treatment of MM with BRAFV600E mutation. Panel sequencing and minimally invasive approaches to diagnosis and disease monitoring can significantly contribute to personalized care and a better understanding of disease dynamics.