Current Testing Practices for t(11;14) Rearrangements in Patients with Newly Diagnosed Multiple Myeloma in the United States

Background: Despite an improvement in the awareness and use of precision medicine and molecular testing in hematological cancers, there are still significant disparities in biomarker testing. This ultimately leads to inequality in molecular testing access and can lead to suboptimal medical care for some patients, who do not receive the most appropriate and effective therapy. Venetoclax is a selective BCL-2 inhibitor and has shown promising antimyeloma activity in patients with t(11;14) multiple myeloma (MM). t(11;14) is the most frequent chromosomal translocation in MM reported in approximately 15-20% of newly diagnosed MM patients (NDMM) (Kumar et al. Blood 2017). In this study, we assessed current t(11;14)(q13;q32) testing practices in patients with NDMM in the United States (US) to gain insights on challenges for biomarker testing and equitable access to precision medicine.

Methods: A retrospective, real-world evidence study was conducted between January and December 2021 using the Diaceutics DXRX Data Repository database. DXRX is a patient-level claims- and laboratory-linked dataset covering more than 4000 laboratories and 360 million patient lives between 2011 and 2022 in the US. Eligible patients were identified using International Classification of Disease (ICD) codes for NDMM (ICD-10 code C90.0). A 2-year lookback was utilized to ensure patients were not in remission or relapse (ICD-10 codes C90.01, C90.02). Percentages were used to describe study population characteristics. t(11;14) and plasma cell enrichment (PCE) testing rates were estimated using descriptive statistics for the entire cohort as well as for race/ethnicity subgroups. PCE testing was considered as it contributes to increasing sensitivity of testing.

Results: We identified 27,586 eligible patients with NDMM. The median age at diagnosis was 70 years (interquartile range: 65-75) and 45% were female. Among the eligible patients, 69% (n=19,034) specifically received t(11;14) testing, within 1 month from diagnosis to testing.

Fluorescence in situ hybridization (FISH; dual color, dual fusion probe and immunoglobin [IG] break apart) was the most commonly utilized technology (89%; n=16,940) for detecting t(11;14); next-generation sequencing panels were limited (<1%) in utilization. Confirmatory reflex testing with a t(11;14) dual probe following positive IG break apart was not performed in 17% (n=3235) of patients. In patients who were tested with the t(11;14) dual probe FISH assay, less than half (40.9%) were tested for t(11;14) with PCE. Results of the FISH assay were available for 4941 patients. A lower positivity rate was observed with non-PCE testing (13.1%; n=647) compared with those utilizing PCE (16.8%; n=830), p=0.494.

Testing rates of t(11;14) in an academic setting were 72% (n=10,659) vs 64% (n=8374) in the community setting, p<0.0001. PCE was performed on only 24.9% (n=2093) of patients in a community setting vs 61% (n=6502) of samples in an academic setting, p<0.0001.

For the subgroup analysis, race/ethnicity data were available for 9245 patients with NDMM; 75.7% were White, 15.9% were Black, 2.6% were Asian, 2% were Hispanic, and 3.2% were classified as other. t(11;14) testing rates were higher for patients who were White (72.8%) compared with the minority groups (66.9% for patients who were Black, 68.8% for patients who were Asian, and 65.7% for patients who were Hispanic). The t(11;14) testing setting for minority group patients was community (62%) vs academic (38%).

Conclusions: Notable variations in t(11;14) testing patterns were observed among patients with NDMM in different care settings and racial/ethnic groups. There is a clear unmet need for standardization across academic and community settings to mitigate suboptimal testing methodologies that could impact treatment decision-making and patient outcomes. From our study, there is a clear need to improve t(11;14) testing rates as the clinical utility changes from a prognostic to predictive biomarker with the availability of personalized healthcare options. Education of PCE utilization for physicians, especially community-based pathologists and laboratories, will be essential to reduce false negatives and inequalities in optimal testing, especially PCE in ethnic minorities in the US.

Baughn:Roche-Genentech: Consultancy. Mearns:Genentech: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Nixon:Roche / Genentech: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Chopra:Genentech Inc. (Roche): Current Employment; Roche, BMS, Amgen: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Patents & Royalties: Publication number: 20210100805 Publication number: 20200405737 Patent number: 10695352 Patent number: 10653710 Publication number: 20180303840 Publication number: 20180296583. Girvan:Eli Lilly: Current equity holder in publicly-traded company, Ended employment in the past 24 months; AbbVie: Current Employment, Current equity holder in publicly-traded company. Cornell:AbbVie: Current Employment, Current equity holder in publicly-traded company. Saxena:Diaceutics PLC: Current Employment, Current equity holder in publicly-traded company. Slifko:Diaceutics PLC: Current Employment, Current equity holder in publicly-traded company. Clark:Diaceutics: Current Employment, Current equity holder in publicly-traded company. Kumar:AbbVie,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive,: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE,: Research Funding; MedImmune/Astra Zeneca,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck,: Research Funding; Novartis,: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee.