Multiple myeloma gammopathies

Functional profiling of venetoclax sensitivity can predict clinical response in multiple myeloma

Article metrics

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2


  1. 1.

    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.

  2. 2.

    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.

  3. 3.

    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.

  4. 4.

    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.

  5. 5.

    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.

  6. 6.

    Friedman AA, Letai A, Fisher DE, Flaherty KT. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015;15:747–56.

  7. 7.

    Letai A. Functional precision cancer medicine-moving beyond pure genomics. Nat Med. 2017;23:1028–35.

  8. 8.

    Cheng ML, Solit DB. Opportunities and challenges in genomic sequencing for precision cancer care. Ann Intern Med. 2018;168:221–2.

  9. 9.

    Moscow JA, Fojo T, Schilsky RL. The evidence framework for precision cancer medicine. Nat Rev Clin Oncol. 2018;15:183–92.

  10. 10.

    Leverson JD. Chemical parsing: dissecting cell dependencies with a toolkit of selective BCL-2 family inhibitors. Mol Cell Oncol. 2016;3:e1050155.

  11. 11.

    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.

  12. 12.

    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.

  13. 13.

    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.

  14. 14.

    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.

  15. 15.

    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.

  16. 16.

    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.

Download references


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

Correspondence to Lawrence H. Boise.

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

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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) doi:10.1038/s41375-018-0374-8

Download citation

Further reading