ModifiedPremera BluecrossPolicy 5.01.24

Monoclonal Antibodies for the Treatment of Lymphoma

Defines medical necessity, investigational uses, documentation, and coding for monoclonal antibodies used to treat lymphoma and related lymphoid malignancies under the medical benefit.

Policy Summary

PayerPremera Bluecross

PolicyMonoclonal Antibodies for the Treatment of Lymphoma

Policy CodePolicy 5.01.24

Change TypeCoverage and operational updates (product relocations, formulary status, added indications)

Effective DateJun 1, 2026

Next Review Date

Key ActionObtain prior authorization and submit medical records demonstrating criteria are met, including documentation of prior therapies and CD20 expression when required.

SourceLink

POLICY UPDATE CHANGES

Moved Columvi, Epkinly, and Lunsumio from the Monoclonal Antibodies policy to the Bispecific Antibodies policy (5.01.650).

Moved Adcetris and Polivy from the Monoclonal Antibodies policy to the Antibody-Drug Conjugate policy (5.01.582).

Updated Polivy coverage to include use in combination with R-CHP for previously untreated DLBCL or HGBL with IPI >= 2.

Added coverage criteria for Columvi for adults with relapsed/refractory DLBCL or LBCL arising from follicular lymphoma after two or more systemic therapies.

Updated product formulary status: Ruxience listed as non-preferred (earlier) and later Riabni changed from non-preferred to preferred; Rituxan and Rituxan Hycela updated to require trial with all preferred rituximab products.

Clarified non-formulary exception review authorizations may be approved up to 12 months for all drugs listed in this policy (2025 update).

6 monthsinitial auth

12 months

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Coverage Criteria and Medical Necessity

Product-specific medical necessity

Covered when the following product-specific conditions are met:

Rituximab biosimilars and formulations - first-line: Riabni (rituximab-arrx), Ruxience (rituximab-pvvr), and Truxima (rituximab-abbs) are CD20-directed cytolytic antibodies and may be considered medically necessary for labeled indications including Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). These agents may also be considered medically necessary for treatment of B‑cell or other lymphoid malignancies with documented CD20 antigen expression (see enumerated list).

Not subject to site-of-service review for lymphoma.

Rituxan (rituximab) — second-line: Rituxan (rituximab) may be considered medically necessary for labeled indications (NHL, CLL) AND the individual has had an inadequate response or intolerance to Riabni (rituximab-arrx), Ruxience (rituximab-pvvr), AND Truxima (rituximab-abbs).

May be used for the same off-label CD20-expressing indications listed for biosimilars.

Rituxan Hycela (subcutaneous rituximab) — second-line with exception: Rituxan Hycela (rituximab and hyaluronidase human) may be considered medically necessary for adult individuals with documented CD20 antigen expression for specified conditions (e.g., FL, DLBCL in combination with CHOP or other anthracycline-based regimens, CLL in combination with FC) when the individual has had an inadequate response or intolerance to Riabni, Ruxience, AND Truxima AND documentation is provided; an exception may be granted for difficult venous access.documented CD20 antigen expression

Specific labeled/off-label uses and combinations are enumerated in policy (e.g., use with CHOP for previously untreated DLBCL).

Monjuvi (tafasitamab-cxix) may be considered medically necessary for adults with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy/HSCT when used in combination with lenalidomide after at least two prior therapies; Monjuvi in combination with rituximab and lenalidomide may be considered medically necessary for relapsed/refractory follicular lymphoma per inMIND trial criteria after prior therapy as specified.>=18 years; prior therapy requirements per indication

Age and prior-line requirements aligned to trial populations (L-MIND, inMIND).

Arzerra (ofatumumab) may be considered medically necessary for specified CLL situations described in the product labeling (e.g., in combination with chlorambucil when fludarabine is inappropriate; with fludarabine+cyclophosphamide for relapsed CLL; extended treatment after >=2 lines; refractory CLL to fludarabine and alemtuzumab).

Evidence for some Arzerra indications is limited to uncontrolled studies; see investigational considerations where controlled-trial evidence is required.

Investigational indications

Not covered/Investigational when:

Investigational: no CD20 expression: Treatment of lymphoid B-cell malignancies that do not express CD20 antigen is considered investigational for rituximab products.

All other uses of the listed rituximab products are considered investigational unless listed in a related medical policy.

Evidence-based coverage considerations

Evidence summary-based coverage considerations for monoclonal antibodies in B‑cell malignancies:

SC vs IV rituximab: Randomized trials (SABRINA in FL; MabEase in DLBCL; SAWYER in CLL) demonstrated similar efficacy and safety for an IV lead‑in followed by subcutaneous rituximab compared with IV rituximab; primary endpoints met non‑inferiority or comparable response rates in these populations.

SABRINA: overall response ~84.9% IV vs 84.4% SC (FL, n=410); MabEase: CR/Cru 42.4% IV vs 50.6% SC (DLBCL, n=576); SAWYER: PK non-inferiority with higher troughs for SC (CLL, n=176).

Ofatumumab (Arzerra) evidence limitations: Evidence for Arzerra is primarily from uncontrolled clinical studies in refractory CLL with approximate response rates reported; controlled trials are lacking to establish superiority or survival benefit and this may constrain coverage where higher‑level evidence is needed.

Refer to single-arm and uncontrolled study data described in the policy evidence section.

Tafasitamab (Monjuvi) clinical data: Phase 2 L‑MIND and Phase 3 inMIND data support tafasitamab combinations: L‑MIND (R/R DLBCL ineligible for HSCT) demonstrated ORR 60% (43% CR) with median DOR ~22 months and median PFS ~12 months; inMIND (R/R FL) showed significant PFS improvement with Monjuvi+rituximab+lenalidomide versus control (median PFS 22.4 vs 13.9 months; HR 0.43).

Notable Coverage Criteria and Product Placement

Selected coverage updates and criteria changes noted in these chunks:

Polivy frontline indication: Polivy (polatuzumab vedotin-piiq) is covered in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for previously untreated DLBCL, NOS or HGBL in adult individuals with an IPI score of 2 or greater.IPI >= 2

Added in 2023 update.

Columvi relapsed/refractory indication: Columvi (glofitamab-gxbm) coverage was added for adult individuals with relapsed or refractory DLBCL, NOS or LBCL arising from follicular lymphoma after two or more lines of systemic therapies.>= 2 prior systemic therapies

Added in the 2023 update; subsequently moved to Bispecific Antibodies policy as noted in later updates.

Rituximab product sequencing and formulary placement: Rituxan and Rituxan Hycela were updated to non-preferred status and now require trial with all preferred rituximab products prior to coverage of non-preferred agents; preferred/non-preferred assignments for rituximab biosimilars have been changed over time per history notes.

Historical coverage actions and formulary/indication updates

Policy history documents additions of medically necessary indications, preferred product status, and movement of specific agents between policies.

Indication and policy movements over time: Multiple agents and indications have been added, updated, or relocated across related policies (examples include addition of Monjuvi and Epkinly coverage, addition then later movement of Columvi, Lunsumio, Adcetris, and Polivy to other specialized policies), reflecting evolving evidence and policy organization.

History entries list specific dates and actions; see history for details.

Formulary and preferred-status changes: Rituximab products have undergone preferred/non-preferred status changes across reviews (e.g., Truxima preferred; Ruxience changed to preferred; Rituxan and Rituxan Hycela designated non-preferred requiring trials of preferred products).

Historical timeline and coding updates documented in history entries.

Treatment of lymphoid B-cell malignancies that do not express CD20 antigen is explicitly designated as investigational for rituximab products (including Riabni, Rituxan, Rituxan Hycela, Ruxience, and Truxima). This investigational stance applies to off‑label uses in CD20‑negative lymphoid B‑cell malignancies; other uses are considered investigational unless a related policy specifies coverage.

Ofatumumab (Arzerra) has evidence limited primarily to uncontrolled clinical studies showing objective responses in some refractory CLL populations; controlled trials and demonstration of survival benefit are lacking. Uses of ofatumumab that are not supported by controlled‑trial evidence and demonstrated survival advantage may be excluded or considered investigational under this policy.

Lumoxiti (moxetumomab pasudotox‑tdfk) was removed and is noted as unavailable after August 2023 because the manufacturer permanently discontinued the product from the US market; as a result, Lumoxiti criteria were removed from this policy.

This medical policy does not apply to Medicare Advantage; coverage determinations remain subject to the limits and conditions of the member's benefit plan and providers should consult the member benefit booklet or contact member services for plan‑specific coverage.

All other uses of the rituximab products listed in this policy that are not specified as covered within this document or a related medical policy are considered investigational. Additionally, formulary and step‑therapy updates (e.g., requirements to trial preferred rituximab products) affect access and do not change the investigational designation for unspecified uses.

There are no new explicit not medically necessary statements introduced in the recent updates; the primary changes are operational and administrative—relocating several agents to related policies, updating formulary/preferred product status, and clarifying coverage and authorization procedures.

Coding and Billing

HCPCS codes referencedHCPCS

J9302	Injection, ofatumumab (Arzerra), 10 mg
J9311	Injection, rituximab 10 mg and hyaluronidase (Rituxan Hycela)
J9312	Injection, rituximab (Rituxan), 10 mg
J9349	Injection, tafasitamab-cxix (Monjuvi), 2 mg
Q5115	Injection, rituximab-abbs, biosimilar (Truxima), 10 mg
Q5119	Injection, rituximab-pvvr, biosimilar (Ruxience), 10 mg
Q5123	Injection, rituximab-arrx, biosimilar (Riabni), 10 mg

HCPCS / historical coding actionsHCPCS

J9311	HCPCS code added (referenced in history)
J9312	HCPCS code added (referenced in history)
J9313	HCPCS code added (referenced in history)
J9042	HCPCS code referenced (removed later when agent moved)
J9999	HCPCS code referenced/removed
Q5115	HCPCS code added
Q5119	HCPCS code added
J3590	HCPCS code added and removed in history for various agents
C9070	HCPCS code added then term date set and removed
J9349	HCPCS code added

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Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization for tafasitamab regimens

Prior authorization required for tafasitamab-based regimens. Authorization decisions should reflect the clinical trial populations that support tafasitamab use (for example, combinations with lenalidomide and populations ineligible for HSCT or those evaluated in L-MIND and inMIND). Initial approvals may be granted up to 6 months; re-authorization up to 12 months is allowable when drug-specific criteria are met and chart notes document ongoing clinical benefit.

Apply prior authorization consistent with tafasitamab clinical trial populations (e.g., tafasitamab + lenalidomide in R/R DLBCL; tafasitamab combinations evaluated in FL).
Initial authorization up to 6 months; re-authorization up to 12 months if criteria met and clinical response documented.

Denial Risk

Limited controlled evidence for Arzerra (ofatumumab)

Ofatumumab (Arzerra) has limited evidence from uncontrolled clinical studies; available data suggest activity in some refractory CLL and rituximab-refractory disease but lack controlled trial evidence demonstrating superiority or survival benefit. This limited controlled evidence should inform coverage decisions and may be a reason to restrict coverage compared with alternatives that have stronger evidence.

Covered Regimens and Indications

Regimen	Indication	Coverage status
Rituxan Hycela or IV rituximab in combination with CHOP or other anthracycline-based chemotherapy	Previously untreated diffuse large B‑cell lymphoma (DLBCL)	Covered

Regimen	Indication	Coverage status
IV rituximab or initial IV lead‑in followed by subcutaneous Rituxan Hycela plus chemotherapy (as studied in SABRINA)	Previously untreated CD20‑positive follicular lymphoma (FL)	Covered

Regimen	Indication	Coverage status
Rituximab added to CHOP chemotherapy (rituximab + CHOP)	Intermediate or aggressive non‑Hodgkin lymphoma; mantle cell lymphoma	Covered

Regimen	Indication	Coverage status
Tafasitamab + lenalidomide (L‑MIND regimen)	Relapsed/refractory DLBCL in adults ineligible for high‑dose chemotherapy/HSCT	Covered
Tafasitamab + rituximab + lenalidomide (inMIND combination)	Relapsed/refractory follicular lymphoma when used per trial criteria	Covered

Regimen	Indication	Coverage status
IV rituximab (standard formulation)	CD20‑positive NHL and CLL as labeled or per policy criteria	Covered
IV lead‑in dose followed by SC Rituxan Hycela (studies: SABRINA, MabEase, SAWYER)	Follicular lymphoma, DLBCL, CLL (as studied)	Covered

Regimen	Indication	Coverage status
Ofatumumab monotherapy (Arzerra)	Refractory chronic lymphocytic leukemia (CLL) in uncontrolled study populations	Experimental

Regimen	Indication	Coverage status
Polivy (polatuzumab vedotin‑piiq) in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R‑CHP)	Previously untreated high‑risk DLBCL or high‑grade B‑cell lymphoma (HGBL) with IPI ≥ 2	Covered

Regimen	Indication	Coverage status
Polivy used as bridging therapy prior to planned CD19 CAR‑T treatment	Individuals requiring bridging therapy before CAR‑T infusion	Neutral

Regimen	Indication	Coverage status
Polivy + R‑CHP (polatuzumab vedotin‑piiq with rituximab product, cyclophosphamide, doxorubicin, prednisone)	Previously untreated adult DLBCL or HGBL with International Prognostic Index (IPI) ≥ 2	Covered

Regimen	Indication	Coverage status
Rituxan Hycela (subcutaneous rituximab) — requires documented CD20 antigen expression	Indications per Rituxan Hycela labeling and policy (e.g., FL, DLBCL, CLL) with documented CD20 expression	Covered (formulation‑specific requirement)

Regimen	Indication	Coverage status
Epkinly (epcoritamab‑bysp) — coverage added in policy history	Certain adults with DLBCL; later expanded to relapsed/refractory FL per history	Covered (per policy additions)

Regimen	Indication	Coverage status
Monjuvi (tafasitamab‑cxix) — tafasitamab combinations (with lenalidomide; with rituximab + lenalidomide)	Relapsed/refractory DLBCL (L‑MIND) and later added indication for relapsed/refractory FL (inMIND) per policy history	Covered

Regimen	Indication	Coverage status
Columvi (glofitamab‑gxbm) — coverage for relapsed/refractory DLBCL or LBCL arising from follicular lymphoma after ≥2 prior systemic therapies (policy moved)	Relapsed/refractory DLBCL or LBCL after two or more lines of systemic therapy	Covered (moved to bispecific antibodies policy)

Line-of-Therapy Criteria

first-line | second-line

First-line: Riabni, Ruxience, and Truxima may be used first-line for labeled indications (NHL, CLL) and for listed off-label CD20-expressing malignancies.

Second-line (Rituxan): Rituxan may be used as second-line when the individual has had inadequate response or intolerance to Riabni, Ruxience, AND Truxima.

Second-line (Rituxan Hycela): Rituxan Hycela may be used in adults for specified indications when the individual has had inadequate response or intolerance to Riabni, Ruxience, AND Truxima; exception allowed for difficult venous access.

second-line | later

Biomarker and Diagnostic Requirements

inv-46: CD20 — documented CD20 antigen expression

RequirementDocumented CD20 antigen expression is required for use of CD20-directed therapies (rituximab products).

Applicable productsRiabni (rituximab-arrx), Rituxan (rituximab), Ruxience (rituximab-pvvr), Truxima (rituximab-abbs), Rituxan Hycela (rituximab and hyaluronidase).

Relevant indicationsNon-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and other B‑cell or lymphoid malignancies with CD20 expression as listed in policy (e.g., FL, DLBCL, mantle cell, MALT).

inv-47: CD19 — CD19 biomarker reference

BiomarkerCD19 is the target antigen for tafasitamab (Monjuvi).

Associated productMonjuvi (tafasitamab-cxix) — a CD19-directed cytolytic antibody indicated in combination with lenalidomide for relapsed/refractory DLBCL (per labeling).

Definitions and Product Notes

inv-32: Rituximab and biosimilars — CD20-directed cytolytic antibody

DefinitionRituximab and biosimilars are CD20-directed cytolytic antibodies used to treat CD20-expressing B‑cell malignancies (e.g., NHL, CLL).

Products includedRiabni (rituximab-arrx), Rituxan (rituximab), Ruxience (rituximab-pvvr), Truxima (rituximab-abbs), Rituxan Hycela (subcutaneous formulation).

Policy notePreferred-product sequencing and trials of biosimilars may be required per formulary updates (trial/failure of preferred products before non-preferred use).

inv-33: Tafasitamab (Monjuvi) — CD19-directed cytolytic antibody

DefinitionTafasitamab (Monjuvi) is a CD19-directed cytolytic monoclonal antibody indicated in combination with lenalidomide for relapsed/refractory DLBCL.

Clinical evidence

Policy Summary

PayerPremera Bluecross

PolicyMonoclonal Antibodies for the Treatment of Lymphoma

Policy CodePolicy 5.01.24

Change TypeCoverage and operational updates (product relocations, formulary status, added indications)

Effective DateJun 1, 2026

Next Review Date

Key ActionObtain prior authorization and submit medical records demonstrating criteria are met, including documentation of prior therapies and CD20 expression when required.

SourceLink

On This Page

Note

Obsolete references and archived policies

Remove or avoid reliance on obsolete references. References to archived policies (for example, BCBSA Reference Policy 2.03.05) have been removed from this policy; requests citing archived policy language may be denied as obsolete. Providers should reference the current policy language and recent policy history when submitting prior authorization requests.

Archived references (e.g., BCBSA Ref. Policy 2.03.05) are no longer applicable.
Do not submit requests based solely on archived policy language; use current policy criteria and history.

Documentation Required

Documentation for tafasitamab-based regimens

When requesting tafasitamab-containing regimens, submit complete clinical documentation demonstrating that the member meets drug-specific criteria and matches the supporting trial population. Required documentation includes prior lines of therapy, eligibility or ineligibility for HSCT when relevant, response to prior therapies, and detailed clinic notes.

Office visit notes with diagnosis, relevant history, physical exam, and medication history.
Documentation of prior lines of systemic therapy and reasons for ineligibility for HSCT when applicable (e.g., L-MIND eligibility).
Treatment response documentation (e.g., baseline and on-treatment assessments).

Step Therapy

Required trial of preferred biosimilars before alternate formulations

Prior inadequate response or intolerance to listed biosimilars (preferred rituximab products) may be required before coverage of non-preferred or alternate rituximab formulations. The policy requires trial and failure of preferred rituximab products (e.g., Ruxience, Truxima) prior to approval of non-preferred agents unless an exception (such as difficult venous access) is documented.

Document prior trial and inadequate response or intolerance to all preferred rituximab products (e.g., Ruxience, Truxima) when requesting Rituxan or Rituxan Hycela.
Exception may be granted for difficult venous access—provide supporting documentation.

Step Therapy

Step-therapy context for tafasitamab

Step-therapy and comparative-effectiveness context should be considered when evaluating tafasitamab requests. Evidence compares tafasitamab regimens to other options (including CAR-T therapies and polatuzumab-based regimens); response rates and prior lines of therapy in pivotal trials should guide placement in the treatment sequence.

Consider CAR-T (higher reported response rates) and polatuzumab + bendamustine + rituximab data in the treatment sequencing discussion.
Document prior therapies and why tafasitamab is preferred for this patient given comparative evidence and eligibility for other options.

inv-35: Monjuvi (tafasitamab‑cxix) — Anti‑CD19 monoclonal antibody evaluated alone and with lenalidomide

Mechanism/IndicationMonjuvi (tafasitamab-cxix) is an anti‑CD19 monoclonal antibody evaluated alone and in combination with lenalidomide for relapsed/refractory DLBCL.

Key trialL‑MIND (Phase 2) in 81 adults showed ORR 60% (43% CR) with tafasitamab + lenalidomide; maintenance tafasitamab continued until progression in responders.

Additional datainMIND (Phase 3) provided randomized evidence for FL when combined with rituximab + lenalidomide and supports expanded FL indication and safety data (n=546 safety dataset).

inv-36: Arzerra (ofatumumab) — Anti‑CD20 monoclonal antibody with limited evidence from uncontrolled studies for refractory CLL

AgentArzerra (ofatumumab) is an anti‑CD20 monoclonal antibody.

Evidence summaryEvidence for Arzerra efficacy is limited primarily to uncontrolled studies (approx. 50% objective response in fludarabine- or alemtuzumab-refractory CLL); controlled trials are lacking to establish superiority or survival benefit.

Coverage implicationLimited controlled-trial evidence may constrain coverage where higher-level evidence is required; review documentation per policy.

Monoclonal antibodies used in B‑cell malignancies include agents directed at surface antigens such as CD20 (e.g., rituximab and biosimilars) and CD19 (e.g., tafasitamab). These antibodies mediate cytolysis of malignant lymphoid cells via immune effector mechanisms and are deployed according to antigen expression and trial‑supported indications. For CD20‑directed agents, documentation of CD20 antigen expression is required for certain formulations (for example, Rituxan Hycela) and clinical benefit has been established in multiple randomized trials for combinations such as rituximab plus CHOP in aggressive NHL and in trials comparing IV and SC rituximab formulations.