Paving the way to precision medicine in multiple myeloma

Inam, Shafqat; Ross, Jeremy A.; Touzeau, Cyrille; Moreau, Philippe; Kumar, Shaji; Harrison, Simon

doi:10.1080/17474086.2021.1905515

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…Moreover, we have shown the potential of integrating VACR, CDW, and pharmacy databases to create high‐performing algorithms with which to phenotype patients with a particular disease. With further advances in tumor cytogenetics and biomarkers and greater synergy across structured and unstructured data, 24 more sophisticated algorithms can be developed to advance precision medicine and redefine clinical phenotypes of patients with MM treated and followed in VA and other large databases. Future studies should also validate algorithms that measure important treatment outcomes—such as duration, discontinuation, and MM relapse—taking care to capture both internal information in VA data and external information from other data sources (e.g., CMS).…”

Section: Discussionmentioning

confidence: 99%

Validation of algorithms to select patients with multiple myeloma and patients initiating myeloma treatment in the national Veterans Affairs Healthcare System

DuMontier

Hassan

et al. 2022

Pharmacoepidemiology and Drug

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Background: We aimed to evaluate and compare the performance of multiple myeloma (MM) selection algorithms for use in Veterans Affairs (VA) research.Methods: Using the VA Corporate Data Warehouse (CDW), the VA Cancer Registry (VACR), and VA pharmacy data, we randomly selected 500 patients from 01/01/1999 to 06/01/2021 who had (1) either one MM diagnostic code OR were listed in the VACR as having MM AND (2) at least one MM treatment code. A team reviewed oncology notes for each veteran to annotate details regarding MM diagnosis and initial treatment within VA. We evaluated inter-annotator agreement and compared the performance of four published algorithms (two developed and validated external to VA data and two used in VA data).Results: A total of 859 patients were reviewed to obtain 500 patients who were annotated as having MM and initiating MM treatment in VA. Agreement was high among annotators for all variables: MM diagnosis (98.3% agreement, Kappa = 0.93); initial treatment in VA (91.8% agreement; Kappa = 0.77); and initial treatment classification (87.6% agreement; Kappa = 0.86). VA Algorithms were more specific and had higher PPVs than non-VA algorithms for both MM diagnosis and initial treatment in VA. We developed the "VA Recommended Algorithm," which had the highest PPV among all algorithms in identifying patients diagnosed with MM (PPV = 0.98, 95% CI = 0.95-0.99) and in identifying patients who initiated their MM treatment in VA (PPV = 0.93, 95% CI = 0.90-0.96). Conclusion:Our VA Recommended Algorithm optimizes sensitivity and PPV for cohort selection and treatment classification.

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Section: Discussionmentioning

confidence: 99%

Validation of algorithms to select patients with multiple myeloma and patients initiating myeloma treatment in the national Veterans Affairs Healthcare System

DuMontier

Hassan

et al. 2022

Pharmacoepidemiology and Drug

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“… 2 , 3 About 20% of MM patients harbor t(11;14) translocation, and they demonstrate overexpression of BCL-2. 4 , 5 Preclinical studies indicate that venetoclax is capable of inducing apoptosis in plasma cell lines dependent on BCL-2 for survival. 6 , 7 For these reasons, although venetoclax has not been approved by the Food and Drug Administration (FDA) for the treatment of MM, a growing number of studies are investigating its efficacy and safety as an alternative antitumor strategy to treat RRMM, especially in patients with t(11;14).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

Lin

Xing

et al. 2023

Therapeutic Advances in Hematology

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Background: Patients with relapsed/refractory multiple myeloma (RRMM) usually have dismal prognostic outcomes. Venetoclax, a selective inhibitor of antiapoptotic protein B-cell lymphoma-2 (BCL-2), demonstrates antimyeloma activity in plasma cells with t(11;14) or high BCL-2 expression. Objectives: This meta-analysis aimed to investigate the efficacy and safety of venetoclax-based therapy in RRMM. Design: This is a meta-analysis study. Data Sources and Methods: PubMed, Embase, and Cochrane were searched for studies published up to 20 December 2021. Overall response rate (ORR), rate of very good partial response or better (≧VGPR), and complete response (CR) rate were pooled with the random-effects model. Safety was evaluated by the incidences of grade ≧3 adverse events. Subgroup analysis and meta-regression were performed to identify the causes of heterogeneities. All the analyses were conducted by STATA 15.0 software. Results: A total of 14 studies with 713 patients were included for analysis. The pooled ORR, rate of ≧VGPR, and CR for all patients were 59% [95% confidence interval (CI) = 45–71%], 38% (95% CI = 26–51%), and 17% (95% CI = 10–26%), respectively. The median progression-free survival (PFS) ranged from 2.0 months to not reached (NR), and the median overall survival (OS) ranged from 12.0 months to NR. Meta-regression showed that patients treated with more drugs combined or less heavily pretreated had higher response rates. Patients with t(11;14) had superior ORR [relative risk (RR) = 1.47, 95% CI = 1.05–2.07], ≧VGPR (RR = 1.71, 95% CI = 1.12–2.60), CR (RR = 1.86, 95% CI = 1.34–2.57), PFS [hazard ratio (HR) = 0.47, 95% CI = 0.30–0.65], and OS (HR = 0.30, 95% CI = 0.08–0.52) compared with patients without t(11;14). Most grade ≧3 adverse events were hematologic, gastrointestinal, and infectious related and were manageable. Conclusion: Venetoclax-based therapy is an effective and safe option for RRMM patients, especially those with t(11;14).

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Paving the way to precision medicine in multiple myeloma

Cited by 2 publications

References 19 publications

Validation of algorithms to select patients with multiple myeloma and patients initiating myeloma treatment in the national Veterans Affairs Healthcare System

Validation of algorithms to select patients with multiple myeloma and patients initiating myeloma treatment in the national Veterans Affairs Healthcare System

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

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