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Bortezomib/bendamustine/dexamethasone induced good PR in refractory relapse post auto-SCT with constitutive RAS activation due to V600E BRAF mutation

Bone Marrow Transplantation volume 49, pages 1545–1547 (2014)Cite this article

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Despite recent major therapeutic advances in multiple myeloma, refractory disease relapse/progression, especially after auto-SCT, remains an unmet challenge in the field. Genetically, frequent RAS mutation has been reported in myeloma.1 Moreover, patients with NRAS mutation were associated with reduced sensitivity to bortezomib.2 Hence, targeted therapy against RAS activation is of interest. Sorafenib is a multi-kinase inhibitor targeting RAS activation.3 On the other hand, bortezomib has been shown to restore chemosensitivty to alkylators in refractory myeloma.4 Herein, we report a bortezomib- and lenalidomide-refractory myeloma patient with ERK1/2 activation due to V600E BRAF mutation, in which sorafenib resulted in non-durable response, but subsequent bortezomib/bendamustine/dexamethasone (VBD) combination rendered a PR.

This patient had proven refractory to both bortezomib and lenalidomide even during induction. Despite achieving a very good PR after auto-SCT, his disease progressed 9 months post auto-SCT, suggestive of highly refractory myeloma, which was evidenced by the aggressive disease progression with rapidly rising IgG levels. Moreover, as his disease progressed within 9 months after auto-SCT, hence myeloma cells were likely chemorefractory to high-dose melphalan in addition to bortezomib, thalidomide and lenalidomide. Unfortunately, carfilzomib and pomalidomide were not available. Therefore, novel therapies instead of conventional chemotherapy were considered at relapse.

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  1. Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China

    C S Chim & K Y Wong

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Correspondence to C S Chim.

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Chim, C., Wong, K. Bortezomib/bendamustine/dexamethasone induced good PR in refractory relapse post auto-SCT with constitutive RAS activation due to V600E BRAF mutation. Bone Marrow Transplant 49, 1545–1547 (2014). https://doi.org/10.1038/bmt.2014.192

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