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Timing Is Everything: Advancing Genomic Testing in Hematologic Malignancies
Rapid NGS and streamlined workflows are critical to delivering timely, actionable genomic insights in blood cancers, but access, reimbursement, and expertise gaps persist.
Cancer care has changed substantially in the past few years, and molecular diagnostics have been central to that shift. However, hematological malignancies, such as acute myeloid leukemia (AML), multiple myeloma, and certain lymphomas, remain challenging to manage.
In rapidly progressing blood cancers, treatment decisions often need to be made within days, and genomic data is most valuable when biomarker results are available early enough to inform the initial treatment plan. The challenge in precision oncology is delivering actionable molecular insights to clinicians quickly enough. Rapid, reliable diagnostic tools are essential to ensure the right information is available precisely when it matters most for patient care.
Molecular characterization with precision diagnostics
Hematologic malignancies frequently demonstrate complex clonal architectures, with co-occurring mutations that can influence disease behavior, including treatment response. This means 2 patients with the same diagnosis may end up needing different treatment plans.
Comprehensive, multi-gene testing with sensitive next-generation sequencing (NGS) panels allows simultaneous detection of clinically relevant variants in a single assay. When designed appropriately, targeted panels balance breadth and depth, capturing key alterations while maintaining analytical sensitivity for low variant allele frequency (VAF) events. The utility of such testing is highly dependent on timing.
Establishing clinical value with a rapid turnaround time
The 2022 European LeukemiaNet (ELN) recommendations emphasize that molecular results identifying therapeutically actionable targets should be available as quickly as possible—ideally within 3–5 days—to inform initial treatment strategy.1
Rapid NGS can meaningfully reduce the turnaround time to actionable results while providing broad molecular profiling, helping clinicians align patients with therapies targeted to their specific alterations. For instance, early identification of FLT3 or IDH1 mutations can support timely consideration of approved target therapies in the appropriate setting or match patients to an optimal clinical trial. Rapid-NGS panels complement other established core diagnostics, such as cytogenetics and flow cytometry, by capturing additional molecular alterations that are not detectable by these tests.
Similar considerations can apply across other hematologic malignancies, where molecular features are increasingly incorporated into classifications, risk models, and treatment selection. Depending on panel design and sensitivity, NGS can also support diagnosis in challenging cases (e.g., suspected “triple-negative” myeloproliferative neoplasm or complex lymphoma cases), detect low-level adverse subclonal variants (e.g., TP53), Ig/TCR clonality assessment, informing risk and treatment decisions. In selected settings, profiling may also identify trackable biomarkers for minimal residual disease response monitoring.
In each case, for rapid testing to translate into clinical value, results need to be clear, consistent, and integrated into the established clinical workflows. Unclear reporting can delay decisions and may require confirmatory or additional testing, adding time in situations where decisions are time-sensitive.
Barriers beyond technology
The technical capability for rapid NGS now exists in many regions. Automation, streamlined library preparation, and integrated bioinformatics have reduced hands-on time and improved reproducibility.
Yet, adoption remains uneven. Often, barriers to precision medicine in hematology are operational: staffing, interpretation capacity, validation and reporting, and funding or reimbursement determine whether genomic data arrives in time and is usable.
Running these technologies requires specialist expertise and resources to validate assays, manage high-throughput analysis, and interpret findings. However, expertise is not evenly available across institutions. While professional guidelines exist, reporting practices vary across laboratories.
Roadblocks around affordability and equitable access are persistent challenges across healthcare that also complicate the adoption of NGS. While large academic centers are often better positioned to build and maintain in-house NGS services, community hospitals and rural clinics rely more on regional networks or external testing and may have limited local specialist capacity. As a result, access to rapid genomic profiling can vary widely.
Another contributing factor to the slower integration of NGS technologies is that coverage and funding haven’t been consistent across payers and health systems. Even when testing is clinically indicated, inconsistent coverage and prior authorization can delay ordering and make it difficult for laboratories to sustain rapid, in-house workflows and for smaller labs to justify the investment.
Enabling broader access to rapid molecular profiling
Wider access to NGS technologies is achievable. Automated specimen-to-report systems can reduce manual steps, support more predictable turnaround times, and enable standardized analysis and reporting across laboratories. While automation does not solve everything, such as reimbursement, local policies, and the availability of clinical expertise, it can make decentralized in-house rapid molecular profiling more feasible.
Curated disease-focused targeted panels are often the most practical choice for rapid clinical decision-making. By concentrating on clinically actionable genes, they reduce interpretive burden and allow faster analysis without compromising clinical relevance. Partnerships with academic institutions and regional networks can also extend interpretive expertise to community settings, helping bridge disparities in access.
The precision-medicine trials program myeloMATCH (Myeloid Malignancies Molecular Analysis for Therapy Choice) in AML and MDS illustrates how rapid molecular profiling can be operationalized at scale. Early reports demonstrate the feasibility of collecting and returning clinical and molecular data quickly to support the matching of patients to genomically defined treatment studies.
Closing the gap between capability and access
Further transformation in the care of hematologic malignancies is likely to occur over the coming years, as rapid genomic testing becomes more integrated into routine practice. For many disease settings, the technology is ready for broader use, and the body of clinical evidence supporting its use continues to expand.
Because access, turnaround time, and consistency still vary across health systems, closing this gap will require investment in molecular diagnostic capacity, including validated workflows, quality systems, staffing, and automation. Equally important are education and ongoing support so clinicians and laboratory teams can order and interpret results consistently. Clearer reimbursement pathways and continued progress toward more standardized reporting can further reduce delays and variability across sites.
For hematologic malignancies, precision medicine is no longer aspirational—it is increasingly embedded in classification systems, risk models, and many treatment pathways. The remaining imperative is ensuring that genomic insight arrives in time to influence the decisions that matter most.
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