Summary & Overview
CPT 0364U: clonoSEQ® Assay for MRD Monitoring via NGS
CPT code 0364U identifies the clonoSEQ® Assay, a proprietary next-generation sequencing (NGS) test used to detect and monitor minimal residual disease (MRD) in hematolymphoid malignancies via blood or bone marrow specimens. As a PLA code tied to a single manufacturer's assay, it standardizes reporting for a clinically important monitoring tool that can influence treatment decisions and long-term surveillance strategies nationwide. The code matters nationally because MRD status increasingly informs prognosis and therapy selection in hematologic cancers, and clear coding affects coverage, billing consistency, and clinical documentation.
Key payers discussed include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of clinical purpose and service characteristics, payer coverage patterns and benchmarks, applicable billing modifiers and service-line implications, and the clinical context for repeat testing to track disease burden. The publication also summarizes common questions payers consider for NGS-based MRD assays, practical implications for lab and outpatient settings, and where to find additional policy updates. Data not available in the input is noted where relevant.
Billing Code Overview
CPT code 0364U is a Proprietary Laboratory Analyses (PLA) code specific to the clonoSEQ® Assay from Adaptive Biotechnologies. The test uses next-generation sequencing (NGS) to analyze a blood or bone marrow specimen from a hematolymphoid (blood/lymph) cancer patient to identify and track patient-specific clonal DNA sequences associated with the malignancy. Repeated testing enables detection of minimal residual disease (MRD) by measuring persistent or rising levels of these clonal sequences during and after treatment.
Service type: Laboratory — next-generation sequencing-based MRD monitoring
Typical site of service: Clinical laboratory or hospital outpatient laboratory; specimen collection may occur in outpatient clinics or inpatient settings where blood or bone marrow samples are obtained.
Clinical & Coding Specifications
Clinical Context
A typical patient is an adult or pediatric individual diagnosed with a hematolymphoid malignancy (for example, B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, or other lymphoid neoplasms) undergoing systemic therapy or post-transplant surveillance. The treating hematologist/oncologist orders the 0364U clonoSEQ® Assay to quantify minimal residual disease (MRD) by next-generation sequencing (NGS) of rearranged immunoglobulin or T-cell receptor gene sequences in a peripheral blood or bone marrow specimen. The clinical workflow begins with the clinician documenting the indication in the medical record, obtaining informed consent if required, and ordering the test through the institutional or commercial laboratory ordering portal. A phlebotomy or bone marrow collection is performed at the outpatient clinic, infusion center, hospital inpatient unit, or pathology collection site. The specimen is sent to the manufacturer-designated lab for proprietary processing and NGS analysis. Results reporting includes a quantitative MRD level, interpretation of detectable versus undetectable disease, and comparison with prior clonoSEQ® results to inform response assessment and longitudinal monitoring. Typical use cases include assessing depth of response after induction/consolidation therapy, early detection of molecular relapse during surveillance, and post-hematopoietic cell transplant monitoring.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | When billing only the interpretation/analysis component provided by a physician or qualified professional separate from the technical lab processing. |
TC | Technical component | When billing only the laboratory technical component (sequencing, reagents, instrumentation) separate from professional interpretation. |
QK | CLIA waived laboratory personnel technical component | When a specific contractual staffing arrangement or personnel reporting requirement applies (used per payer policy for PLA technical staffing delineation). |
QX | Modifier for assistant-at-surgery (distinct) | Rarely applicable; included for payer systems that require QX for certain delegated services associated with specimen collection when an assistant performs the procedure. |
QY | Modifier for provider-performed microscopy (PPM) — supervisory | When the performing laboratory meets provider-performed microscopy or similar specialty testing supervisory rules per payer guidance. |
62 | Two surgeons | Not typical for this test but used when two physicians share responsibility for specimen collection in unusual operative settings. |
78 | Unplanned return to OR | Not applicable to the assay itself; included for completeness in complex inpatient care episodes involving operative specimen collection. |
80 | Assistant surgeon | See 62 and QX notes; rarely used for procedures related to specimen procurement. |
22 | Increased procedural services | When additional, atypical work is required for specimen procurement or coordination beyond standard expectations and allowed by payer policy. |
52 | Reduced services | When a partial or limited specimen is submitted that reduces the scope of testing performed. |
53 | Discontinued procedure | When the collection procedure was started but discontinued and billing must reflect limited services. |
AS | Physician is present during anesthesia | Used if specimen collection occurs under anesthesia and the physician documents being present per payer rules. |
FY | CLIA-exempt laboratory reporting modifier | Applied per certain payer or contractual reporting rules for proprietary assays processed under specific laboratory arrangements. |
QY | Provider-performed testing supervisory modifier (duplicate listed intentionally per payer systems) | See above entry for QY. |
| Taxonomy Code | Specialty | Notes |
|---|---|---|
| 207RR0500X | Hematology & Oncology | Hematologist-oncologists order and interpret MRD testing for blood cancers. |
| 207L00000X | Hematopathology | Hematopathologists review marrow morphology and coordinate molecular MRD testing. |
| 208000000X | Medical Oncology | Medical oncologists managing systemic therapy use MRD results for treatment decisions. |
| 1223P0001X | Clinical Laboratory | Clinical laboratory directors and molecular diagnostics specialists oversee test performance and reporting. |
| 2082N0402X | Pediatric Hematology-Oncology | Pediatric specialists order clonoSEQ® for children with lymphoid malignancies. |
Related Diagnoses
| ICD-10 Code | Description | Clinical Relevance |
|---|---|---|
C91.10 | Chronic lymphocytic leukemia of unspecified site not having achieved remission | MRD testing used to monitor disease burden and response to therapy in CLL. |
C91.00 | Acute lymphoblastic leukemia not having achieved remission | clonoSEQ® is used to detect residual leukemic clones after induction or consolidation therapy. |
C90.00 | Multiple myeloma not having achieved remission | MRD assessment in bone marrow or peripheral blood informs depth of response in myeloma management. |
C83.30 | Diffuse large B-cell lymphoma, unspecified site | For select lymphomas, MRD testing may be used in clinical follow-up to detect molecular relapse. |
C81.90 | Hodgkin lymphoma, unspecified site | Molecular monitoring may be adjunctive to imaging and clinical assessment in follow-up. |
Related CPT Codes
| CPT Code | Description | Relationship to This Procedure |
|---|---|---|
0364U | clonoSEQ® Assay — NGS-based MRD testing for hematolymphoid cancers (proprietary PLA) | Primary code reported for the proprietary assay performed by Adaptive Biotechnologies; used to bill for sequencing-based MRD quantification. |
88305 | Level IV surgical pathology, gross and microscopic examination | May be billed for bone marrow biopsy specimen pathology examination performed alongside MRD testing when marrow morphology is assessed. |
88005 | Flow cytometry interpretation | Performed in some centers as an alternative or complementary MRD modality; may be billed when flow MRD panels are run in parallel. |
81479 | Unlisted molecular pathology procedure | Occasionally used for additional non-proprietary molecular tests related to disease characterization when no specific CPT exists. |
36415 | Collection of venous blood by venipuncture | Billed for peripheral blood specimen collection for the assay when performed in an outpatient or inpatient setting. |
38221 | Bone marrow biopsy, needle or trocar, single or multiple sites; with or without aspiration | Billed when a bone marrow core biopsy is obtained to provide material for MRD testing and pathology evaluation. |