Precision medicine in hemato-oncology – treatment of refractory multiple myeloma with massive extramedullary involvement using BRAF/ MEK inhibitors

Česká verze

Authors: M. Štork ¹; J. Kotašková ^1,2,3; E. Ondroušková ¹; M. Borský ¹; A. Marečková ¹; N. Sendlerová ¹; J. Mayerová ¹; M. Brada ⁴; I. Boichuk ¹; K. Menšíková ¹; Z. Adam ¹; M. Krejčí ¹; V. Sandecká ¹; Z. Jelínková ⁵; M. Krtička ⁶; V. Nekuda ⁶; M. Bilčíková ¹; V. Hrabčáková ¹; L. Vojtková ¹; M. Jarošová ^1,2,3; P. Šlampa ⁴; L. Pour ¹
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; Středoevropský technologický institut, MU Brno ²; Ústav lékařské genetiky a genomiky, FN Brno ³; Klinika radiační onkologie LF MU a MOÚ Brno ⁴; Klinika popálenin a plastické chirurgie LF MU a FN Brno ⁵; Klinika úrazové chirurgie LF MU a FN Brno ⁶
Published in the journal: Klin Onkol 2025; 38(5): 390-397
Category: Kazuistiky
doi: https://doi.org/10.48095/ccko2025390

Summary

Background: 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. Case: We present a case of a patient with relapsed/refractory MM and extensive EMD in whom a BRAF^V600E 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. Results: 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 BRAF^V600E mutation were also monitored in plasma using cfDNA and digital PCR. Conclusion: This case illustrates the potential of precision therapy in the treatment of MM with BRAF^V600E 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.

Keywords:

precision medicine – Next-generation sequencing – multiple myeloma – BRAF inhibitors

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