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BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis.

Rustad EH, Dai HY, Hov H, Coward E, Beisvag V, Myklebost O, Hovig E, Nakken S, Vodák D, Meza-Zepeda LA, Sandvik AK, Wader KF, Misund K, Sundan A, Aarset H, Waage A - Blood Cancer J (2015)

Bottom Line: In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival.BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors.In particular, a large mutated cell fraction did not correlate with aggressive disease.

View Article: PubMed Central - PubMed

Affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

ABSTRACT
In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival. Biopsies were screened for BRAF V600E by allele-specific real-time PCR (AS-PCR). Positive results were confirmed by immunohistochemistry, Sanger sequencing and, in three patients from whom we had stored purified myeloma cells, whole-exome sequencing. Eleven patients (5.3%) were BRAF V600E mutation positive by AS-PCR and at least one other method. The fraction of mutated cells varied from 4 to 100%. BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors. Progression-free and overall survival were similar in patients with and without the mutation. By this integrated approach, we found that patients with BRAF V600E mutation responded very well to broad acting drugs and there was no relation to prognosis in early-stage myeloma. In particular, a large mutated cell fraction did not correlate with aggressive disease.

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Related in: MedlinePlus

Overall survival in patients with and without BRAF V600E mutation shown by Kaplan–Meier plot.
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fig2: Overall survival in patients with and without BRAF V600E mutation shown by Kaplan–Meier plot.

Mentions: There was no significant difference in PFS (data not shown) or OS (Figure 2) between the BRAF V600E-positive and -negative groups. The result was the same also for five patients harboring BRAF V600E in more than 50% of the plasma cells. There was no difference in the prevalence of EMD (Table 3).


BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis.

Rustad EH, Dai HY, Hov H, Coward E, Beisvag V, Myklebost O, Hovig E, Nakken S, Vodák D, Meza-Zepeda LA, Sandvik AK, Wader KF, Misund K, Sundan A, Aarset H, Waage A - Blood Cancer J (2015)

Overall survival in patients with and without BRAF V600E mutation shown by Kaplan–Meier plot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4382665&req=5

fig2: Overall survival in patients with and without BRAF V600E mutation shown by Kaplan–Meier plot.
Mentions: There was no significant difference in PFS (data not shown) or OS (Figure 2) between the BRAF V600E-positive and -negative groups. The result was the same also for five patients harboring BRAF V600E in more than 50% of the plasma cells. There was no difference in the prevalence of EMD (Table 3).

Bottom Line: In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival.BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors.In particular, a large mutated cell fraction did not correlate with aggressive disease.

View Article: PubMed Central - PubMed

Affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

ABSTRACT
In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival. Biopsies were screened for BRAF V600E by allele-specific real-time PCR (AS-PCR). Positive results were confirmed by immunohistochemistry, Sanger sequencing and, in three patients from whom we had stored purified myeloma cells, whole-exome sequencing. Eleven patients (5.3%) were BRAF V600E mutation positive by AS-PCR and at least one other method. The fraction of mutated cells varied from 4 to 100%. BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors. Progression-free and overall survival were similar in patients with and without the mutation. By this integrated approach, we found that patients with BRAF V600E mutation responded very well to broad acting drugs and there was no relation to prognosis in early-stage myeloma. In particular, a large mutated cell fraction did not correlate with aggressive disease.

Show MeSH
Related in: MedlinePlus