CurrentEmblemHealthPolicy N/A

Zynlonta (loncastuzimab tesirine-lpyl) — Coverage Criteria

Defines clinical coverage criteria, exclusions, and medication management for Zynlonta for treatment of lymphoma, specifying requirements for authorization and supporting evidence; applies to EmblemHealth members managed by Evolent UM.

Policy Summary

PayerEmblemHealth

PolicyZynlonta (loncastuzimab tesirine-lpyl) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJun 28, 2024

Next Review DateJun 12, 2024

Key ActionObtain prior authorization and document CD19+ tumor expression and prior progression on ≥2 systemic therapy lines.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

0.15 mg/kgsingle-dose limit (first 2 cycles)

0.075 mg/kgsingle-dose limit (cycle 3+)

>=2prior therapy lines required

CD19+tumor expression

Coverage Criteria

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DLBCL indication: Member has relapsed or refractory diffuse large B-cell lymphoma (DLBCL NOS, DLBCL arising from low-grade lymphoma, or high-grade B-cell lymphoma)

CD19 expression: CD19+ tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry

Prior therapies: Member has had disease progression on two or more lines of systemic therapies (examples: R-CHOP, R-ICE, R-DHAP, R-ESHAP, R-EPOCH, or R-GDP)>= 2 prior systemic lines

Requests for Zynlonta will be excluded when any of the following apply: the medication is being used on or after disease progression with the same regimen; there is no confirmed documentation of CD19 tumor expression by an accepted test; or the ordered dose exceeds the policy’s single-dose limits of 0.15 mg/kg for the first two cycles or 0.075 mg/kg for cycle 3 and beyond. Prior authorization approval requires documentation of CD19+ disease and prior treatment history (see provider actions), and exceeding these dosing thresholds will result in denial.

Zynlonta use for indications that are off-label or lack sufficient evidence is excluded. The policy defines insufficient evidence as use not supported by CMS-recognized compendia or acceptable peer-reviewed literature and evaluates factors such as whether the patient and regimen are represented in published evidence, whether outcomes are clinically meaningful (for example, ASCO-recommended thresholds such as a hazard ratio < 0.80 or OS/PFS benefit of at least 3 months), study design appropriateness, and the level of evidence (recognizing that non-randomized trials with substantial subject numbers may be supportive while case reports and abstracts without full articles generally are not).

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zynlonta (loncastuzimab tesirine-lpyl). Approvals are contingent on documentation confirming CD19+ relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL) and that the member meets the prior therapy requirements below. Authorization decisions must be supported by FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature per the Medicare Benefit Policy Manual.

A prior authorization request must include documentation of CD19 tumor expression (e.g., bone marrow or peripheral blood flow cytometry).
Provide clinical records showing prior systemic therapies and progression dates.
Cite supporting evidence: FDA label, CMS compendia, NCCN/ASCO guidance, or acceptable peer-reviewed literature.

Prior Authorization

Prior Therapy Requirement

Member must have relapsed or refractory DLBCL and have progressed on two or more lines of systemic therapy prior to use of Zynlonta. Examples of acceptable prior systemic regimens include R-CHOP, R-ICE, R-DHAP, R-ESHAP, R-EPOCH, or R-GDP.

Document at least two prior systemic therapy regimens and evidence of progression after those therapies.
Include regimen names, treatment dates, and objective evidence of progression (imaging reports, clinical notes).

Documentation Required

Documentation & Exclusion Triggers

Requests lacking required documentation or meeting exclusion criteria will be denied. Do not authorize if CD19 expression is not confirmed, dosing exceeds single-dose limits, or therapy is being requested following progression on the same regimen. Ensure supporting literature meets CMS criteria for acceptable evidence.

Exclude requests without confirmed CD19 tumor expression by standard testing.
Exclude requests where dosing exceeds single-dose limits: 0.15 mg/kg (first 2 cycles); 0.075 mg/kg (cycle 3 and beyond).
Exclude investigational or off-label uses lacking sufficient evidence per CMS compendia or acceptable peer-reviewed literature.

Initial Therapy Criteria

Initial coverage criteria

Indication: Monotherapy for CD19+ relapsed/refractory DLBCL

CD19 expression must be demonstrated by flow cytometry in bone marrow or peripheral blood.

Prior therapies: Disease progression on two or more lines of systemic therapy>= 2 prior lines

Examples listed in policy (e.g., R-CHOP, R-ICE, R-DHAP, R-ESHAP, R-EPOCH, R-GDP)

Dosing limits: Single dose limits: 0.15 mg/kg for first 2 cycles; 0.075 mg/kg cycle 3 and beyond

Exceeding these limits is an exclusion per policy.

Continuation Therapy Criteria

Continuation therapy exceptions

Continuation requests for previously used medications may be authorized under limited conditions.

Continuation conditions: Requested medication was used within the last year; member has not experienced disease progression and/or no intolerance to the medication; no additional medications are being added to the continuation request.

Applies to continuation requests for a medication that would otherwise be not approvable.

Step	Requirement
Prior failure requirement	Member must have had disease progression on two or more lines of systemic therapy (examples: R-CHOP, R-ICE, R-DHAP, R-ESHAP, R-EPOCH, or R-GDP)

Definitions

Relapsed/refractory DLBCL definition

Definition of relapsed/refractory DLBCLDiffuse large B‑cell lymphoma not otherwise specified (DLBCL NOS)

DLBCL arising from low‑grade lymphomaDLBCL that has evolved from a prior low‑grade lymphoma

High‑grade B‑cell lymphomaHigh‑grade B‑cell lymphoma presenting with disease progression after prior therapies

CD19+ tumor expression — documentation

Required tumor markerCD19+ tumor expression

Accepted specimen sourcesDemonstrated in bone marrow or peripheral blood

Accepted test methodBy flow cytometry

Background

Zynlonta (loncastuzimab tesirine-lpyl) is an antibody-drug conjugate indicated as monotherapy for patients with CD19-positive relapsed or refractory diffuse large B‑cell lymphoma (DLBCL). The policy references the FDA label and available clinical evidence (including LOTIS‑2) and requires demonstration of CD19 expression and prior systemic therapy failure per the coverage criteria.