This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Kumar S, Kaufman JL, Gasparetto C, Mikhael J, Vij R, Pegourie B, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130:2401–9.
Ni Chonghaile T, Sarosiek KA, Vo TT, Ryan JA, Tammareddi A, Moore Vdel G, et al. Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science. 2011;334:1129–33.
Touzeau C, Dousset C, Le Gouill S, Sampath D, Leverson JD, Souers AJ, et al. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia. 2014;28:210–2.
Matulis SM, Gupta VA, Nooka AK, Hollen HV, Kaufman JL, Lonial S, et al. Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax. Leukemia. 2016;30:1086–93.
Kaufman JL, Gasparetto CJ, Mikhael J, Moreau P, Touzeau C, Vij R, et al. Phase 1 study of venetoclax in combination with dexamethasone as targeted therapy for t(11;14) relapsed/refractory multiple myeloma. Blood. 2017;130:3131.
Friedman AA, Letai A, Fisher DE, Flaherty KT. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015;15:747–56.
Letai A. Functional precision cancer medicine-moving beyond pure genomics. Nat Med. 2017;23:1028–35.
Cheng ML, Solit DB. Opportunities and challenges in genomic sequencing for precision cancer care. Ann Intern Med. 2018;168:221–2.
Moscow JA, Fojo T, Schilsky RL. The evidence framework for precision cancer medicine. Nat Rev Clin Oncol. 2018;15:183–92.
Leverson JD. Chemical parsing: dissecting cell dependencies with a toolkit of selective BCL-2 family inhibitors. Mol Cell Oncol. 2016;3:e1050155.
Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117:112–21.
Touzeau C, Ryan J, Guerriero J, Moreau P, Chonghaile TN, Le Gouill S, et al. BH3 profiling identifies heterogeneous dependency on Bcl-2 family members in multiple myeloma and predicts sensitivity to BH3 mimetics. Leukemia. 2016;30:761–4.
Bodet L, Gomez-Bougie P, Touzeau C, Dousset C, Descamps G, Maiga S, et al. ABT-737 is highly effective against molecular subgroups of multiple myeloma. Blood. 2011;118:3901–10.
Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25:91–101.
Walker BA, Wardell CP, Melchor L, Brioli A, Johnson DC, Kaiser MF, et al. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia. 2014;28:384–90.
Montero J, Sarosiek KA, DeAngelo JD, Maertens O, Ryan J, Ercan D, et al. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. 2015;160:977–89.
Acknowledgements
The authors thank the patients for providing the samples used in this study. They also acknowledge the hard work and dedication of the Winship Myeloma Research Team for consenting patients and collecting samples. Funding was provided by R01 CA192844, P30 CA138292 and the Emory Myeloma Working Group.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
NJB, funding and honorarium from Celgene and Janssen; PM and JDL, employment, Abbvie; LTH, research funding, Abbvie; SL, consultancy, Takeda, Celgene, Novartis, Abbvie, Amgen, Janssen, Bristol-Myers Squibb; AKN, advisory board or consultancy, Amgen, Adaptive Technologies, Janssen, Celgene, Spectrum Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline, Takeda; JLK, Consultancy, Abbvie, Janssen, Bristol-Myers Squibb, Takeda, Data Monitoring Committee, Karyopharm, Pharmacyclics; LHB, consultancy, Abbvie, honorarium, AstraZeneca. The other authors declare that they have no conflict of interest.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Matulis, S.M., Gupta, V.A., Neri, P. et al. Functional profiling of venetoclax sensitivity can predict clinical response in multiple myeloma. Leukemia 33, 1291–1296 (2019). https://doi.org/10.1038/s41375-018-0374-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41375-018-0374-8
This article is cited by
-
Exploiting endogenous and therapy-induced apoptotic vulnerabilities in immunoglobulin light chain amyloidosis with BH3 mimetics
Nature Communications (2022)
-
Venetoclax ex vivo functional profiling predicts improved progression-free survival
Blood Cancer Journal (2022)
-
A pipeline for malignancy and therapy agnostic assessment of cancer drug response using cell mass measurements
Communications Biology (2022)
-
Programmed cell death, redox imbalance, and cancer therapeutics
Apoptosis (2021)
-
Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma
Nature Communications (2020)