TY  - JOUR
A1  - Da Vià, Matteo Claudio
A1  - Solimando, Antonio Giovanni
A1  - Garitano-Trojaola, Andoni
A1  - Barrio, Santiago
A1  - Munawar, Umair
A1  - Strifler, Susanne
A1  - Haertle, Larissa
A1  - Rhodes, Nadine
A1  - Vogt, Cornelia
A1  - Lapa, Constantin
A1  - Beilhack, Andreas
A1  - Rasche, Leo
A1  - Einsele, Hermann
A1  - Kortüm, K. Martin
T1  - CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF‐MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement
JF  - The Oncologist
N2  - Combined MEK‐BRAF inhibition is a well‐established treatment strategy in BRAF‐mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF‐MEK inhibitor treatment are unavailable.

Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high‐risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.
KW  - Multiple myeloma
KW  - Extramedullary disease
KW  - Capicua transcriptional repressor
KW  - Drug resistance
KW  - BRAF mutation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219549
VL  - 25
IS  - 2
ER  -