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. 2022 Aug 4;12(8):115.
doi: 10.1038/s41408-022-00710-9.

Venetoclax ex vivo functional profiling predicts improved progression-free survival

Vikas A Gupta  1 , Shannon M Matulis  2 , Benjamin G Barwick  2 , R Devin Bog  2 , Conrad W Shebelut  3 , Mala Shanmugam  2 , Paola Neri  4 , Nizar J Bahlis  4 , Madhav V Dhodapkar  2 , Leonard T Heffner  2 , Craig C Hofmeister  2 , Nisha S Joseph  2 , Sagar Lonial  2 , Jonathan L Kaufman  2 , David L Jaye  3 , Ajay K Nooka  2 , Lawrence H Boise  5
Affiliations

Venetoclax ex vivo functional profiling predicts improved progression-free survival

Vikas A Gupta et al. Blood Cancer J. .
No abstract available

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Conflict of interest statement

PN serves on advisory boards for BMS, Janssen, and Sanofi. NJB receives honoraria from and serves in a consulting or advisory role for Celgene, Janssen, AbbVie, Amgen, Sanofi, and Takeda. MDV serves on advisory boards for Amgen, Janssen, Roche, and Genentech. CCH has received research grants from Oncolytics Biotech, research and personal grants from Janssen, BMS, Sanofi, Nektar, and Karyopharm, and personal grants from Imbrium and Oncopeptides. LTH receives an honorarium from Kite Pharmaceuticals. SL has consulting or advisory roles with Celgene, Bristol-Myers Squibb, Janssen Oncology, Novartis, GlaxoSmithKline, Amgen, AbbVie, Takeda, Merck, Juno Therapeutics, and receives research funding from Celgene, Bristol-Myers Squibb, and Takeda. AKN has a significant financial interest in Janssen pharmaceuticals and has participated on advisory boards and received honoraria from Janssen, Takeda, Amgen, BMS/Celgene, GSK, Oncopeptides, Karyopharm pharmaceuticals, BeyondSprings, Secura Bio, Sanofi, and Adaptive technologies. JLK receives honoraria from Tecnofarma; research support from BMS, Janssen, Bluebird, Sutro Biopharma, Amgen, Abbvie, Fortis Therapeutics, GSK; consultancy for BMS, Janssen; and data safety monitoring board for TG therapeutics. DLJ serves on the advisory board for Stemline Therapeutics. LHB receives research funding, consultancy, and honoraria from AstraZeneca and performs consultancy for Genentech and Abbvie. The remaining authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. Patient outcomes based on ex vivo venetoclax testing.
Pre-treatment bone marrow aspirates were tested ex vivo for venetoclax sensitivity as described previously [3]. Briefly, buffy coat cells were treated with increasing concentrations of venetoclax for 24 h and then assessed for apoptosis by annexin V staining to determine an IC50. An IC50 of less than 100 nM was considered sensitive, while an IC50 of greater than 100 nM was considered resistant. A Overall response rate for patients with sensitive vs. resistant ex vivo testing. B PFS and C OS of sensitive and resistant patients. D Receiver operating curve for ex vivo testing.
Fig. 2
Fig. 2. Patient outcomes based on BCL2 IHC.
Pre-treatment bone marrow biopsies were co-stained by IHC for BCL2 and CD138 to identify plasma cells. Samples were grouped into low and intermediate/high categories by a pathologist blinded to clinical correlates. A Representative images of bone marrow biopsies with low, intermediate, and high BCL2 (red) staining in CD138 (brown) plasma cells. B PFS of patients with low vs intermediate/high BCL2 staining in plasma cells. C PFS of patients treated with venetoclax having either 2 or greater than two copies of 1q. D Copy Number Alterations (CNA) at chromosome 1q21 and MCL1 expression in 670 Newly Diagnosed Multiple Myeloma (NDMM) cases from the CoMMpass study. (2×, N = 430; 3×, N = 197; 4× N = 43). P values computed using a t test are denoted on top.
See this image and copyright information in PMC

References

    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. doi: 10.1182/blood-2017-06-788786. - DOI - PubMed
    1. Kaufman JL, Gasparetto C, Schjesvold FH, Moreau P, Touzeau C, Facon T, et al. Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma. Am J Hematol. 2021;96:418–27. doi: 10.1002/ajh.26083. - DOI - PMC - PubMed
    1. Matulis SM, Gupta VA, Neri P, Bahlis NJ, Maciag P, Leverson JD, et al. Functional profiling of venetoclax sensitivity can predict clinical response in multiple myeloma. Leukemia. 2019;33:1291–6. doi: 10.1038/s41375-018-0374-8. - DOI - PMC - PubMed
    1. 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. doi: 10.1038/leu.2015.350. - DOI - PMC - PubMed
    1. Gupta VA, Matulis SM, Conage-Pough JE, Nooka AK, Kaufman JL, Lonial S, et al. Bone marrow microenvironment-derived signals induce Mcl-1 dependence in multiple myeloma. Blood. 2017;129:1969–79. doi: 10.1182/blood-2016-10-745059. - DOI - PMC - PubMed

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