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Association details:
| Biomarker: | BCL2 overexpression |
|---|---|
| Cancer: | Multiple Myeloma |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
T(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study
Published date:
11/06/2019
Excerpt:
Adding Ven to Bd demonstrates significant efficacy in pts with RRMM harboring either t(11;14) or tumor cells expressing high levels of BCL2.
DOI:
https://doi.org/10.1182/blood-2019-126094
Trial ID:
Source:
Title:
Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (MM)
Excerpt:
...Very Good Partial Response (VGPR) or better response rate in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression...Progression-free survival (PFS) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression...Duration of overall response (DOR) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression...Time to progression (TTP) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression...Objective response rate (ORR) in participants with relapsed or refractory MM and in a subset of participants with high B-cell lymphocyte-2 (BCL-2) expression...
Secondary therapy:
carfilzomib + dexamethasone
Source:
Title:
A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy
Excerpt:
Progression-Free Survival (PFS) in subjects with high B-cell lymphoma 2 (BCL-2) expression...
Trial ID:
Less C2 evidence
Source:
Title:
1914 Gain of chr1q Portends Poor Outcomes in Multiple Myeloma Patients Treated with Venetoclax
Published date:
11/03/2022
Excerpt:
In this study, we sought to investigate the genomic determinants of response to venetoclax in a real-world setting outside of clinical trials....Our analysis showed a trend towards higher expression of BCL2 (p=0.07) and the BCL2/MCL1 ratio (p=0.07), as well as significant up-regulation of the BCL2/BCL2L1 ratio in patients with higher PFS (p<0.05).
DOI:
https://doi.org/10.1182/blood-2022-166572
Source:
Title:
Assessment of Minimal Residual Disease By Next-Generation Sequencing and Fluorodeoxyglucose-Positron Emission Tomography in Patients with Relapsed/Refractory Multiple Myeloma Treated with Venetoclax in Combination with Carfilzomib and Dexamethasone
Published date:
11/04/2020
Excerpt:
Among t(11;14) pts, ORR was 92%, ≥ VGPR 85%, and ≥CR 54%; while among BCL2 high pts ORR was 86%, ≥ VGPR 77%, and ≥CR 41%....The combination of VenKd demonstrates promising efficacy in pts with R/R MM, including high rates of MRD, particularly in the t(11;14) and BCL2 high subgroups.
Secondary therapy:
carfilzomib + dexamethasone
Source:
Title:
Advances in precision therapy with venetoclax in multiple myeloma with t(11;14) and high BCL2 expression: A systematic review.
Published date:
05/28/2020
Excerpt:
With high BCL2, VEN-Bd achieved ORR of 84% (CR 35%, VGPR 73%) versus placebo (ORR 83%; VGPR 33%) (Bellini 2019).
DOI:
10.1200/JCO.2020.38.15_suppl.e20535
Source:
Title:
2975 Biomarker and Ex Vivo Sensitivity Analysis of Venetoclax (ABT-199/GDC-0199) in Combination with Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Excerpt:
The exploratory biomarker analysis showed that higher BCL-2 gene expression levels at baseline significantly correlated with clinical responses to therapy, with a trend toward increased mToS. Additionally, MM cells treated ex vivo demonstrated greater sensitivity to the combination of VEN/BTZ than to the 2 single agents alone.
Source:
Title:
Venetoclax monotherapy is feasible and efficient in patients with bcl-2 overexpressing relapsed/refractory multiple myeloma at high- risk sites: a case series
Published date:
08/28/2021
Excerpt:
...three cases of bcl-2 IHC positive RRMM patients...two of three patients showed a strong cyclin D1 expression....Regarding the first case, two months after venetoclax beginning, IgG levels dropped to normal range reaching a VGPR (Duration of response (DOR) is 7 months). In the second case a CR was achieved in PET-CT and MRI scans 5 months after beginning of venetoclax treatment (DOR 15 months). A follow-up PET-CT staging of the third case showed a CR of the previously described extramedullary manifestations three months after venetoclax dosing.
Source:
Title:
REVEALING TRANSCRIPTOME DEREGULATION UPON GENOMIC COMPLEXITY IN MULTIPLE MYELOMA.
Published date:
05/14/2020
Excerpt:
...for CYLD we observed upregulation of BCL2, a marker of response to venetoclax….
Source:
Title:
The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma
Excerpt:
...Karpas 620 CCND1 line was selected for its high Bcl-xL expression. Puma and Bim were found associated with both Bcl-2 and Bcl-xL in this cell line. After 6 h of ABT-199 treatment (25 nm), Puma/Bcl-2 and Bim/Bcl-2 complexes were disrupted in contrast to the Bcl-xL heterodimers that were not modified (Figure 1c)....Sensitivity to ABT-199 was significantly associated with higher expression of Bcl-2 (P=0.008) and tended to be associated with a lower Mcl-1 expression (P=0.09) (Supplementary Figure 2).
DOI:
https://dx.doi.org/10.1038%2Fleu.2013.216
