Zynlonta (loncastuximab tesirine-lpyl) — HCPCS J9359

DLBCL R/R salvage landscape — CD19 ADC vs CD79b ADC vs bispecifics NCCN verified May 2026

Zynlonta competes head-to-head with the CD20×CD3 bispecifics in the post-CAR-T / post-second-line space. Polivy is positioned earlier in the sequence.

Zynlonta is the only CD19-directed antibody-drug conjugate approved for R/R DLBCL, with a pyrrolobenzodiazepine (PBD) DNA-crosslinker payload that is mechanistically distinct from the MMAE payload used in Polivy (CD79b ADC) and Adcetris (CD30 ADC). Its label position — monotherapy after ≥2 prior systemic therapies — places it in direct competition with the CD20×CD3 bispecifics (Columvi, Epkinly) and after CAR-T in many treatment pathways.

Position relative to CAR-T

In current NCCN B-cell lymphoma guidelines, Zynlonta is positioned as a treatment option for R/R DLBCL after ≥2 prior systemic therapies, often used post-CAR-T failure or in patients ineligible for CAR-T (age, comorbidities, no available product). The bispecifics share this niche; choice is driven by site capability (CRS monitoring infrastructure), patient access to subcutaneous administration (Epkinly), and prior exposure to CD19-directed therapy (which may make CD19 ADC less attractive after CD19 CAR-T).

CD19+ confirmation is required

Although the FDA label does not require CD19+ testing for treatment initiation, payers routinely request flow cytometry or IHC confirmation of CD19 expression on the lymphoma cells. Document the CD19 positivity in the PA submission and chart. Loss of CD19 expression after prior CD19-directed therapy (e.g., CAR-T) is increasingly recognized and is a reason for treatment failure.

Dosing — the load-then-reduce schedule FDA label Apr 2021

150 mcg/kg cycles 1–2, then 75 mcg/kg cycle 3 and beyond. Both infusions are 30 minutes every dose.

FDA-labeled regimen

Zynlonta is administered IV on day 1 of each 21-day cycle until disease progression or unacceptable toxicity, with a label-mandated dose reduction at cycle 3:

Worked example — first cycle billing for 70 kg patient

Dose modifications — FDA label

• Edema/effusions grade 2: withhold until grade ≤1; resume at same dose with diuretics
• Edema/effusions grade 3+: withhold until grade ≤1, then resume at the next lower dose level (cycle 1–2 reduce from 150 → 75 mcg/kg; cycle 3+ reduce from 75 → 50 mcg/kg)
• ALT/AST >3× ULN (grade 2): withhold until improvement to baseline or ≤ULN, resume at same dose
• ALT/AST >5× ULN (grade 3+): withhold until improvement, resume at lower dose level
• Bilirubin >1.5× ULN (grade 2+): withhold; resume at lower dose level when bilirubin returns to baseline
• ANC <1,000/µL or platelets <25,000/µL: withhold until recovery; resume at lower dose level for recurrent grade 4
• Severe cutaneous reactions / SJS / TEN: permanently discontinue

Adults only — no pediatric indication

Zynlonta is approved for adult patients only. Safety and efficacy in pediatric patients have not been established. Off-label pediatric use will be denied by payers and is not supported by clinical data.

Dexamethasone premedication protocol — mandatory FDA label W&P

The 3-day dex course is label-mandated and the single most common denial trigger when documentation is incomplete.

Schedule by cycle

Billing the dex premedication

• IV dexamethasone: bill J1100 "Injection, dexamethasone sodium phosphate, 1 mg" — each 1 mg = 1 unit; 4 mg = 4 units per dose
• PO dexamethasone: not billed under the medical benefit; the patient fills oral dex via pharmacy (commonly handled by ADC Therapeutics patient support program)
• Inpatient or HOPD-administered IV dex: may be part of facility chemo prep bundle — verify your facility's billing convention

Documentation checklist for PA audit defense

• Dex start date and stop date for each cycle (3 consecutive days)
• Route (PO vs IV), dose, and BID frequency
• Patient confirmation of adherence (especially for self-administered PO course)
• Cycle number tied to each premed course
• Any held doses with clinical justification

NDC reference FDA NDC Directory verified May 2026

Administration codes CPT verified May 2026

Zynlonta is billed under chemotherapy administration codes (complex ADC with cytotoxic PBD payload).

Modifiers CMS verified May 2026

JW — required on virtually every Zynlonta claim

Effective July 1, 2023, CMS requires either the JZ or JW modifier on every single-dose container claim. Because Zynlonta comes only in a 10 mg vial and dosing is weight-based at either 150 mcg/kg or 75 mcg/kg, partial-vial waste occurs at virtually every patient weight. Bill JW with the discarded portion (converted to units at 0.075 mg per unit) on a separate claim line.

Cycle 1–2 worked waste table (150 mcg/kg, 10 mg vials)

Cycle 3+ worked waste table (75 mcg/kg, 10 mg vials)

JZ — only when calculated dose exactly matches a 10 mg multiple

JZ applies when no drug is discarded. For Zynlonta this is uncommon at typical weights but possible (e.g., 100 kg at 150 mcg/kg = 15 mg requires 2 vials with 5 mg waste — not zero; truly zero-waste requires the dose to land exactly on 10, 20, 30 mg, etc.). For most patient weights, you will bill JW instead. One of JZ or JW must be on every J9359 claim.

Modifier 25 — same-day E/M

Use modifier 25 on the E/M code when significant, separately identifiable evaluation and management is performed on the same day as infusion. Routine pre-infusion clinical assessment is bundled with 96413.

340B modifiers (JG, TB)

For 340B-acquired Zynlonta, follow your MAC's current 340B modifier policy. ADC Therapeutics' billing guide does not provide 340B-specific instructions.

ICD-10-CM by indication FY2026 verified May 2026

R/R DLBCL is the only indication. Use site-specific 5th character; document ≥2 prior systemic therapies in PA.

Site of care & place of service Verified May 2026

Zynlonta is administered in outpatient settings — hospital outpatient (HOPD), freestanding ambulatory infusion suites, or oncology offices with chemo infusion infrastructure. The 30-minute infusion duration and lack of CRS monitoring make it suitable for any qualified infusion suite, but ADC-specific monitoring (edema/effusions, hepatic, hematologic) requires staff trained in oncologic adverse event recognition. Home infusion is not appropriate — Zynlonta requires oncology-clinic monitoring capability.

Claim form field mapping ADC Therapeutics 2026

From ADC Therapeutics Patient Support coding & coverage guidance.

Payer policy snapshot + PA criteria Reviewed May 2026

DLBCL pathology with CD19 expression, 2+ prior systemic therapy documentation, and dex premed plan are the core PA elements.

Key PA documentation

• Pathology report confirming DLBCL NOS or HGBCL diagnosis with B-cell phenotype
• CD19 expression confirmation (flow cytometry or IHC) — especially after prior CD19-directed therapy
• Prior treatment history with regimens, response, and dates documenting ≥2 prior systemic lines
• Dexamethasone premedication plan (4 mg BID × 3 days starting day before each infusion)
• Baseline labs: CBC, comprehensive metabolic panel, LFTs (ALT/AST/bilirubin); echocardiogram if indicated
• Performance status (ECOG 0–2 typical)
• Adult age confirmation (no pediatric indication)

Step therapy

Generally NOT required for FDA-labeled R/R DLBCL use, since the indication itself requires ≥2 prior systemic therapies — step therapy is essentially built into the label requirement. Some payers position bispecifics (Columvi, Epkinly) or CAR-T as preferred 3L options and may require failure or contraindication to those before approving Zynlonta — verify per-payer.

Medicare reimbursement CMS Q2 2026 (live)

Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.

Coverage

No NCD specific to loncastuximab tesirine. Coverage falls under MAC LCDs for biologics and the generic drug-coverage framework. All MACs cover J9359 for the FDA-approved on-label indication (R/R DLBCL after ≥2 prior systemic therapies) with appropriate ICD-10 and prior treatment documentation. Some MACs request affirmative dex premedication plan documentation in the patient record.

Code history

• J9359 — permanent code, effective January 1, 2022 (initial FDA approval April 23, 2021; pre-permanent-code interim period used C9085 transitional, then unclassified J3490/J9999)
• HCPCS unit = 0.075 mg = 75 micrograms (per CMS HCPCS file)

Patient assistance — ADC Therapeutics Patient Support ADC Therapeutics verified May 2026

• ADC Therapeutics Patient Support: 1-855-690-0340 (Monday–Friday, 8 AM–8 PM ET) — benefits investigation, prior authorization assistance, appeal support, dex premed coordination
• Zynlonta Co-Pay Assistance Program: commercial copay support for eligible commercially-insured patients (excludes Medicare, Medicaid, Tricare, VA, federal program patients). Annual maximum verified at enrollment.
• ADC Therapeutics Patient Assistance Program: free product for uninsured / underinsured patients meeting income requirements (typically ≤500% FPL)
• Foundations: for Medicare patients, refer to PAN Foundation, HealthWell Foundation, CancerCare, Leukemia & Lymphoma Society Co-Pay Assistance Program — verify open lymphoma funds quarterly
• Web: zynlontahcp.com/patient-support (HCP) and zynlonta.com (patient)

Common denials & how to fix them

Frequently asked questions

What is the HCPCS code for Zynlonta?

Zynlonta (loncastuximab tesirine-lpyl) is billed under HCPCS J9359 — "Injection, loncastuximab tesirine-lpyl, 0.075 mg." Each 0.075 mg (75 mcg) equals one billable unit. Standard dosing is 150 mcg/kg IV every 21 days for cycles 1–2, then 75 mcg/kg IV every 21 days for cycle 3 and beyond, for R/R DLBCL monotherapy after ≥2 prior systemic therapies.

Why does the Zynlonta dose drop from 150 mcg/kg to 75 mcg/kg after cycle 2?

The FDA label specifies 150 mcg/kg on day 1 of the first two 21-day cycles, then 75 mcg/kg on day 1 of cycle 3 and each subsequent cycle. The higher loading dose drives the initial CD19-directed cytotoxic response from the PBD payload; the lower maintenance dose preserves activity while reducing cumulative toxicity (edema/effusions, myelosuppression, hepatotoxicity). A cycle 3 dose billed at the cycle 1 dose level is a common denial trigger — audit cycle counter on every claim.

How many units do I bill for a Zynlonta dose?

Each unit equals 0.075 mg. For a 70 kg patient in cycle 1 at 150 mcg/kg, the dose is 10.5 mg = 140 units (10.5 ÷ 0.075). Zynlonta comes only in a 10 mg single-dose vial, so 10.5 mg requires 2 vials (20 mg dispensed) with 9.5 mg discarded — bill JW for 127 units of waste (9.5 ÷ 0.075, rounded up) on a separate claim line. Cycle 3+ at 75 mcg/kg for the same patient is 5.25 mg = 70 units, with 1 vial and 4.75 mg / 64-unit JW waste.

Why is the 3-day dexamethasone premedication so important for billing?

The FDA label mandates dexamethasone 4 mg PO or IV BID for 3 days starting the day before each Zynlonta infusion. The premedication reduces incidence of cutaneous reactions and edema/effusions tied to the PBD payload. Missing or incomplete dex premed documentation is the single most common Zynlonta denial reason — chart the start and stop dates and bill the premed dexamethasone separately under J1100 (each 1 mg) if IV.

What administration CPT do I use for Zynlonta?

CPT 96413 — chemo IV initial. Zynlonta infusion is 30 minutes every dose (no extended first-dose duration), so 96413 alone covers each cycle without needing 96415. Zynlonta is a complex monoclonal antibody-drug conjugate with a PBD cytotoxic payload — chemo admin codes apply, not 96365.

What is the Medicare reimbursement for J9359?

For Q2 2026, the Medicare Part B payment limit for J9359 is $221.493 per 0.075 mg unit (ASP + 6%). A 140-unit cycle 1–2 dose (70 kg patient at 150 mcg/kg) reimburses at approximately $31,009.02; a 70-unit cycle 3+ dose (70 kg patient at 75 mcg/kg) reimburses at approximately $15,504.51. JW waste is reimbursed separately at the same per-unit rate. ASP is updated quarterly by CMS.

How does Zynlonta compare to Polivy and the DLBCL bispecifics?

Zynlonta is a CD19-directed ADC with a PBD DNA-crosslinker payload, used as monotherapy in R/R DLBCL after 2+ prior systemic therapies. Polivy (J9309, polatuzumab vedotin) is a CD79b ADC used earlier in the sequence — 1L combo (POLARIX R-CHP) or 3L+ with bendamustine + rituximab. The CD20×CD3 bispecifics Columvi (J9286) and Epkinly (J9321) also occupy the R/R 3L+ space as monotherapy with step-up dosing and CRS monitoring requirements. Zynlonta is operationally simpler (30-min infusion, no step-up, no CRS) but carries strict dex premedication requirements bispecifics do not.

Is Zynlonta approved for pediatric patients?

No. Zynlonta is approved for adult patients only. Safety and efficacy in pediatric patients have not been established. Off-label pediatric use will be denied by payers and is not supported by clinical data.

What is the LOTIS-7 confirmatory trial?

Zynlonta's April 2021 FDA approval was granted under the accelerated-approval pathway based on the single-arm LOTIS-2 Phase II trial. LOTIS-7 is the current Phase Ib/II post-marketing confirmatory trial, evaluating loncastuximab tesirine in combination with other anti-CD20 or BCL2-pathway agents in R/R DLBCL. LOTIS-5 (Zynlonta + rituximab vs R-GemOx) was the prior planned confirmatory trial but was halted in 2023; ADC Therapeutics shifted the confirmatory commitment to LOTIS-7. Until accelerated approval converts to full approval, some payers may require enhanced PA documentation.

Source documents

1. ADC Therapeutics Patient Support — Zynlonta HCP page
   Phone 1-855-690-0340; Co-Pay Assistance Program; Patient Assistance Program for uninsured
2. DailyMed — ZYNLONTA (loncastuximab tesirine-lpyl) full prescribing information
   Current FDA-approved label revised February 26, 2026 (setid af54af12-3edf-4301-8bc5-0446bc813c1d); BLA 761196; April 23, 2021 accelerated approval for R/R LBCL after ≥2 prior lines. Accelerated approval status confirmed — not withdrawn as of label date; confirmatory benefit pending.
3. ADC Therapeutics — Zynlonta Prescribing Information PDF
4. Caimi et al. — Loncastuximab tesirine in relapsed or refractory DLBCL (LOTIS-2)
   Lancet Oncology 2021; single-arm Phase II trial supporting accelerated approval, n=145
5. FDA — April 23, 2021 accelerated approval announcement
   BLA 761196 accelerated approval based on LOTIS-2
6. LOTIS-7 confirmatory trial (NCT04970901)
   Phase Ib/II of loncastuximab tesirine in combinations for R/R B-cell NHL
7. CMS — Medicare Part B Drug ASP Pricing File
   Q2 2026 quarterly file, effective April 1 – June 30, 2026; J9359 = 0.075 mg per unit
8. SEER CanMED — HCPCS J9359 reference
   Permanent code effective January 1, 2022
9. NCCN Clinical Practice Guidelines — B-Cell Lymphomas
   DLBCL R/R 3L+ recommendations including Zynlonta monotherapy, comparison with bispecifics and CAR-T
10. UnitedHealthcare — Oncology Medication Clinical Coverage Policy
11. Aetna CPB — Antineoplastic Agents (covers loncastuximab tesirine)
12. FDA National Drug Code Directory

About this page

We maintain this page as a living reference. Medicare ASP pricing is bound to our underlying CareCost data layer and refreshes automatically when CMS publishes new quarterly files. Coding and policy content is reviewed at least quarterly and updated whenever a source document changes.

Found an error? Email hello@carecostestimate.com.

Refresh cadence

Reviewer

Change log

• May 23, 2026 — SME audit pass. Added verified DailyMed setid af54af12-3edf-4301-8bc5-0446bc813c1d (label revised February 26, 2026). Confirmed accelerated approval still in force (not withdrawn); confirmatory clinical benefit verification still pending. ASP confirmed Q2 2026 $221.493 per 0.075 mg unit.
• May 22, 2026 — Initial publication. ASP data: Q2 2026 ($221.493 per 0.075 mg unit). Manufacturer source: ADC Therapeutics Patient Support 2026. FDA label: April 23, 2021 accelerated approval (BLA 761196) for R/R DLBCL after ≥2 prior systemic therapies. Confirmatory trial: LOTIS-7 (NCT04970901). HCPCS J9359 permanent code effective January 1, 2022.

Methodology

Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File. Payer policies are read directly from each payer's published medical/pharmacy policy documents. Indication list is verified against the current FDA label revision and NCCN B-Cell Lymphoma Guidelines. We do not paraphrase from billing-software vendor blogs.