Reference Detail

Ref Type

Journal Article

PMID

(36608320)

Authors

Giesen N, Chatterjee M, Scheid C, Poos AM, Besemer B, Miah K, Benner A, Becker N, Moehler T, Metzler I, Khandanpour C, Seidel-Glaetzer A, Trautmann-Grill K, Kortüm KM, Müller-Tidow C, Mechtersheimer G, Goeppert B, Stenzinger A, Weinhold N, Goldschmidt H, Weisel K, Raab MS

Title

A phase 2 clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Blood	141	14	2023 Apr 06	1685-1690	Blood

URL

Abstract Text

Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily. The primary end point was the overall response rate achieved within the first year after start of treatment according to International Myeloma Working Group criteria. Twelve RRMM patients with a median of 5 prior lines of therapy were enrolled. The overall response rate was 83.3%, with 10 patients achieving at least a partial response. The median progression-free survival was 5.6 months, and overall survival was 55% at 24 months. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E-mutated RRMM, and it represents a successful targeted precision medicine approach in this disease. This trial was registered at www.clinicaltrials.gov as #NCT02834364.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	multiple myeloma	sensitive	Binimetinib + Encorafenib	Phase II	Actionable	In a Phase II trial (BIRMA), Mektovi (binimetinib) plus Braftovi (encorafenib) treatment demonstrated safety and efficacy in relapsed/refractory multiple myeloma patients with BRAF V600E, with an overall response rate of 83% (10/12, 1 complete response (CR), 2 near-CR, 6 very good partial responses (PR), and 1 PR), a median duration of response of 4.8 mo, a median progression-free survival of 5.6 mo, and a median overall survival not reached but 66% at 12 mo and 55% at 24 mo (PMID: 36608320; NCT02834364).	36608320