Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2021020
Category:	Pharmacy
Initiated:	June 2021
Last Review:	March 2025

Polatuzumab Vedotin-piiq (e.g., Polivy)

Description:

Polatuzumab vedotin-piiq is a CD79b-directed antibody–drug conjugate [a humanized igG1 antibody specific for CD79b and a small molecule, monomethyl auristatin E (MMAE), a microtubule-disrupting agent]. The monoclonal antibody binds to CD79b, a B-cell specific surface protein, which is a component of the B-cell receptor. Upon binding CD79b, polatuzumab vedotin-piiq is internalized, and the linker is cleaved by lysosomal proteases to enable intracellular delivery of MMAE. MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis. (Polivy, 2023)

Regulatory Status

In June 2019, Polatuzumab vedotin-piiq (e.g., Polatuzumab vedotin) has been approved by FDA and indicated in combination with bendamustine and a rituximab product for the treatment of adult individuals with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies.

Accelerated approval was granted for this indication based on complete response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

In April 2023, Polatuzumab vedotin-piiq (e.g., Polatuzumab vedotin) has been approved by FDA and indicated in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone for the treatment of adult individuals who have previously untreated diffuse large B-cell lymphoma (not otherwise specified) or high-grade B-cell lymphoma with international prognostic index score of two or greater. This FDA decision converted the accelerated approval of polatuzumab in combination with bendamustine and rituximab for relapsed or refractory DLBCL after at least two prior therapies to regular approval.

The National Comprehensive Cancer Network® (NCCN) also has additional category 2A recommendations for the treatment of:

1. Cases ineligible for HSCT with relapsed or refractory high-grade B-cell lymphoma with translocations of MYC and BCL2 and/or BCL6 (after ≥2 prior lines of therapy).

2. Cases of other types of B-cell lymphoma including follicular lymphoma, AIDS-related lymphomas, and B-Cell post-transplant lymphoproliferative disorders.

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.

The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.

Effective March 5, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Polatuzumab vedotin-piiq (e.g., Polivy) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following indications when ALL the following criteria are met:

For FDA labeled indications, Polatuzumab vedotin-piiq (e.g., Polivy) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.

For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication in the dosage and administration section.

FDA Labeled Indications:

The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication below with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”)].

STANDARD REVIEW for up to 12 months:

1. Individual is age 18 years of age or older (Polivy, 2023); AND

2. Polatuzumab Vedotin-piiq (e.g., Polivy) will be used:

a. In combination with rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adults who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater(Polivy, 2023); OR

b. In combination with bendamustine and a rituximab product for the treatment of adults with relapsed or refractory DLBCL, NOS, after at least two prior therapies(Polivy, 2023).

Off-label Indications:

The use of this drug for off-label indications not listed below is subject to policy 2000030.

STANDARD REVIEW for up to 12 months:

The following indications are covered when the individual meets the related NCCN category 1 or 2A recommendations specific to the indications below (e.g., histology, cancer staging, surgical status, mono- or combination therapy, and previous lines of therapy):

1. B-Cell Lymphomas:

a. Diffuse Large B-Cell Lymphoma (NCCN 1 and 2A); OR

b. Histologic Transformation of Indolent Lymphomas to Diffuse Large B-Cell Lymphoma (NCCN 1 and 2A); OR

c. High-Grade B-Cell Lymphomas (NCCN 2A); OR

d. HIV-Related B-Cell Lymphomas (NCCN 2A; OR

e. Post-Transplant Lymphoproliferative Disorders (NCCN 2A).

Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications.

Policy Guidelines

The International Prognostic Index for Diffuse Large B-cell Lymphoma (Ruppert, 2020) predicts overall and progression-free survival in DLBCL based on risk factors. Scores of 0-1 are in low-risk group, score 2 is in low-intermediate group risk, score 3 is in high-intermediate group risk and scores 4-5 are in high group risk.

Scores from the following categories are added up:

1 point for age older than 60 years
1 point for Ann Arbor stage II or IV (disease involvement on both sides of diaphragm or involvement of extranodal sites)
1 point for ECOG performance status greater than 2
1 point for serum LDH level higher than normal
1 point for more than one extranodal site (e.g., bone marrow, GI tract, liver, lung, CNS, skin, testes, Waldeyer’s ring).

smIPI definition: Stage-adjusted IPI is calculated by assigning one point for each of the following (max 4 points):

Age > 60 years
Stage II disease
Elevated serum lactate dehydrogenase (LDH)
ECOG performance status of two or above

Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG-ACRIN Cancer Research Group, 2022)

0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities; Up and about more than 50% of waking hours
3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4 Completely disabled; Cannot carry out any selfcare; Totally confined to bed or chair
5 Dead

Dosage and Administration

Dosing per FDA Guidelines unless otherwise specified below.

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product.

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone.

Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.

Polatuzumab vedotin-piiq is available as injection: 30 mg or 140 mg as a lyophilized powder in a single-dose vial.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Polatuzumab vedotin-piiq (e.g., Polivy), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, Polatuzumab vedotin-piiq (e.g., Polivy), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective June 2024 to March 4, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.

For off label indications, authorizations will not exceed 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles OR maximum recommended doses as outlined in dosage and administration.

Polatuzumab vedotin-piiq meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following indications when ALL the following criteria are met:

DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of diffuse large b-cell lymphoma; AND

2. Polatuzumab vedotin will be used as a first-line therapy component along with rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen for (NCCN 1):

a. Stage I-II (excluding stage II with extensive mesenteric disease) for stage modified International Prognostic Index (smIPI) score larger than 1; OR

b. Stage II (with extensive mesenteric disease) or stage III-IV for International Prognostic Index (IPI) score 2 and greater (see policy guidelines); OR

3. Polatuzumab vedotin will be used as a single agent or in combination with bendamustine and/or rituximab as second-line and subsequent therapy if no intention to proceed to transplant for (NCCN 2A):

a. Relapsed disease more than 12 months after completion of first-line therapy; OR

b, Primary refractory disease or relapsed disease less than 12 months after completion of first-line therapy in non-candidates for CAR T-cell therapy; OR

c. Alternative systemic therapy for relapsed or refractory disease in non-candidates for CAR T-cell therapy; OR

4. Polatuzumab vedotin will be used as a bridging option with or without bendamustine or rituximab as clinically indicated for primary refractory disease or relapsed disease less than 12 months after completion of first-line therapy until CAR T-cell product is available (NCCN 2A); OR

5. Polatuzumab vedotin will be used as a treatment of histologic transformation of follicular or marginal zone lymphoma to DLBCL or high-grade B-cell lymphoma with MYC and BCL6 and without BCL2 rearrangements after minimal or no prior therapy along with rituximab, cyclophosphamide, doxorubicin, and prednisone in individual with International Prognostic Index (IPI) score of 2 and higher (NCCN 1); OR

6. Polatuzumab vedotin will be used as a treatment for histologic transformation of indolent lymphomas DLBCL as a single agent or in combination with bendamustine and/or rituximab if individual has been previously treated with an anthracycline-based regimen and no intention has been made to proceed to transplant where (NCCN 2A):

a. Used as additional therapy for partial response, no response, progressive or relapsed disease following chemoimmunotherapy for histologic transformation of follicular or marginal zone lymphomas after minimal or no prior therapy; OR

b. Used as therapy for histologic transformation of follicular or marginal zone lymphomas after multiple lines of prior therapies including 2 or more chemoimmunotherapy regiments for indolent or transformed disease.

HIGH-GRADE B-CELL LYMPHOMAS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of high-grade B-cell lymphoma; AND

2. Polatuzumab vedotin will be used as a single agent or in combination with bendamustine and/or rituximab as second-line and subsequent therapy if no intention to proceed to transplant (NCCN 2A):

a. Relapsed or refractory disease longer than>12 months after completion of first-line therapy; OR

b. Primary refractory disease or relapsed disease, longer than 12 months after completion of first-line therapy if no intention to proceed to CAR T-cell therapy; OR

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy.; OR

3. Used with or without bendamustine and with or without rituximab as clinically indicated as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease <12 months after completion of first line therapy. (NCCN 2A).

HIV- RELATED B-CELL LYMPHOMAS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of HIV-related diffuse large B-cell lymphoma or primary effusion lymphoma or HHV8-positive diffuse large B-cell lymphoma that is not otherwise specified; AND

2. Polatuzumab vedotin will be used as a second line and subsequent therapy as a single agent or in combination with bendamustine and/or rituximab or without rituximab for relapse of HIV-related plasmablastic lymphoma if no intention to proceed to transplant for (NCCN 2A):

a. Relapsed or refractory disease longer than>12 months after completion of first-line therapy; OR

b. Primary refractory disease or relapsed disease <12 months after completion f first-line therapy if not intention to proceed to CAR T-cell therapy; OR

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed CAR T-cell therapy; OR

3. Polatuzumab vedotin will be used a single agent or in combination with bendamustine and/or rituximab as clinically indicated as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease less than <12 months after completion of first-line therapy (NCCN 2A).

POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of a monomorphic post-transplant lymphoproliferative disorder (PTLD); AND

2. Polatuzumab vedotin will be used as a second line and subsequent therapy as a single agent or with bendamustine and/or rituximab if no intention to proceed to transplant (NCCN 2A):

a. For relapsed disease if longer than>12 months after completion of initial treatment with chemoimmunotherapy; OR

b. For primary refractory disease or relapsed disease less than <12 months after completion of initial treatment with chemoimmunotherapy if no intention to proceed to CAR T-cell therapy; OR c. As alternative systemic therapy for relapsed/refractory disease if no intention ot to proceed to CAR T-cell therapy.; OR

3. Used as clinically indicated as a single agent or in combination with bendamustine and/or rituximab as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease less than<12 months after completion of initial treatment with chemoimmunotherapy (NCCN 2A).

The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).

Policy Guidelines

Scores from the following categories are added up:

1 point for age older than 60 years

1 point for Ann Arbor stage II or IV (disease involvement on both sides of diaphragm or involvement of extranodal sites)

1 point for ECOG performance status greater than 2

1 point for serum LDH level higher than normal

1 point for more than one extranodal site (e.g., bone marrow, GI tract, liver, lung, CNS, skin, testes, Waldeyer’s ring).

smIPI definition: Stage-adjusted IPI is calculated by assigning one point for each of the following (max 4 points):

age > 60 years
stage II disease
elevated serum lactate dehydrogenase (LDH)
ECOG performance status of two or above

Dosage and Administration

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product.

Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.

Polatuzumab vedotin-piiq is available as injection: 30 mg or 140 mg as a lyophilized powder in a single-dose vial.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, Polatuzumab vedotin-piiq is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective April 2024 to May 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.

DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of diffuse large b-cell lymphoma; AND

2. Polatuzumab vedotin will be used as a first-line therapy component along with rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen for (NCCN 1):

a. Stage I-II (excluding stage II with extensive mesenteric disease) for stage modified International Prognostic Index (smIPI) score larger than 1; OR

b. Stage II (with extensive mesenteric disease) or stage III-IV for International Prognostic Index (IPI) score 2 and greater (see policy guidelines); OR

3. Polatuzumab vedotin will be used as a single agent or in combination with bendamustine and/or rituximab as second-line and subsequent therapy if no intention to proceed to transplant for (NCCN 2A):

a. Relapsed disease more than 12 months after completion of first-line therapy; OR

b, Primary refractory disease or relapsed disease less than 12 months after completion of first-line therapy in non-candidates for CAR T-cell therapy; OR

c. Alternative systemic therapy for relapsed or refractory disease in non-candidates for CAR T-cell therapy; OR

4. Polatuzumab vedotin will be used as a bridging option with or without bendamustine or rituximab as clinically indicated for primary refractory disease or relapsed disease less than 12 months after completion of first-line therapy until CAR T-cell product is available (NCCN 2A); OR

5. Polatuzumab vedotin will be used as a treatment of histologic transformation of follicular or marginal zone lymphoma to DLBCL or high-grade B-cell lymphoma with MYC and BCL6 and without BCL2 rearrangements after minimal or no prior therapy along with rituximab, cyclophosphamide, doxorubicin, and prednisone in individual with International Prognostic Index (IPI) score of 2 and higher (NCCN 1); OR

6. Polatuzumab vedotin will be used as a treatment for histologic transformation of indolent lymphomas DLBCL as a single agent or in combination with bendamustine and/or rituximab if individual has been previously treated with an anthracycline-based regimen and no intention has been made to proceed to transplant where (NCCN 2A):

a. Used as additional therapy for partial response, no response, progressive or relapsed disease following chemoimmunotherapy for histologic transformation of follicular or marginal zone lymphomas after minimal or no prior therapy; OR

b. Used as therapy for histologic transformation of follicular or marginal zone lymphomas after multiple lines of prior therapies including 2 or more chemoimmunotherapy regiments for indolent or transformed disease.

HIGH-GRADE B-CELL LYMPHOMAS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of high-grade B-cell lymphoma; AND

2. Polatuzumab vedotin will be used as a single agent or in combination with bendamustine and/or rituximab as second-line and subsequent therapy if no intention to proceed to transplant (NCCN 2A):

a. Relapsed or refractory disease longer than>12 months after completion of first-line therapy; OR

b. Primary refractory disease or relapsed disease, longer than 12 months after completion of first-line therapy if no intention to proceed to CAR T-cell therapy; OR

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy.; OR

3. Used with or without bendamustine and with or without rituximab as clinically indicated as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease <12 months after completion of first line therapy. (NCCN 2A).

HIV- RELATED B-CELL LYMPHOMAS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of HIV-related diffuse large B-cell lymphoma or primary effusion lymphoma or HHV8-positive diffuse large B-cell lymphoma that is not otherwise specified; AND

2. Polatuzumab vedotin will be used as a second line and subsequent therapy as a single agent or in combination with bendamustine and/or rituximab or without rituximab for relapse of HIV-related plasmablastic lymphoma if no intention to proceed to transplant for (NCCN 2A):

a. Relapsed or refractory disease longer than>12 months after completion of first-line therapy; OR

b. Primary refractory disease or relapsed disease <12 months after completion f first-line therapy if not intention to proceed to CAR T-cell therapy; OR

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed CAR T-cell therapy; OR

3. Polatuzumab vedotin will be used a single agent or in combination with bendamustine and/or rituximab as clinically indicated as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease less than <12 months after completion of first-line therapy (NCCN 2A).

POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual has a diagnosis of a monomorphic post-transplant lymphoproliferative disorder (PTLD); AND

2. Polatuzumab vedotin will be used as a second line and subsequent therapy as a single agent or with bendamustine and/or rituximab if no intention to proceed to transplant (NCCN 2A):

a. For relapsed disease if longer than>12 months after completion of initial treatment with chemoimmunotherapy; OR

b. For primary refractory disease or relapsed disease less than <12 months after completion of initial treatment with chemoimmunotherapy if no intention to proceed to CAR T-cell therapy; OR c. As alternative systemic therapy for relapsed/refractory disease if no intention ot to proceed to CAR T-cell therapy.; OR

3. Used as clinically indicated as a single agent or in combination with bendamustine and/or rituximab as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease less than<12 months after completion of initial treatment with chemoimmunotherapy (NCCN 2A).

Policy Guidelines

Scores from the following categories are added up:

1 point for age older than 60 years

1 point for Ann Arbor stage II or IV (disease involvement on both sides of diaphragm or involvement of extranodal sites)

1 point for ECOG performance status greater than 2

1 point for serum LDH level higher than normal

1 point for more than one extranodal site (e.g., bone marrow, GI tract, liver, lung, CNS, skin, testes, Waldeyer’s ring).

Dosage and Administration

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product.

Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.

Polatuzumab vedotin-piiq is available as injection: 30 mg or 140 mg as a lyophilized powder in a single-dose vial.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

Effective March 2023 - March 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following indications when specified criteria are met:

B-Cell Lymphomas-Follicular Lymphoma

1. Used as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)as subsequent therapy for no response, relapsed, or progressive disease in individuals with indications for treatment (NCCN 2A).

2. Must be dosed in accordance with the FDA label.

B-Cell Lymphomas- Histologic Transformation of Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

1. Preferred first-line therapy for stage II with extensive mesenteric disease or stage III-IV disease as a component of Pola-R-CHP (polatuzumab vedotin-piiq, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen for IPI >2. (NCCN 1).

2. Preferred as a single agent or in combination with bendamustine and/or rituximab as second-line and subsequent therapy if no intention to proceed to transplant for (NCCN 2A):

a. Relapsed or refractory disease >12 months after completion of first-line therapy.

b. Primarcy refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy if no intention to proceed to CAR T-cell therapy.

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy.

3. Used with or without bendamustine and with or without rituximab as clinically indicated as a bridging option for primary refractory disease or relapsed disease <12 months after completion of first-line therapy until CAR T-cell product is available. (NCCN 2A).

d. Must be dosed in accordance with the FDA label.

B-Cell Lymphomas-Diffuse Large B-Cell Lymphoma

1. Preferred as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)as second-line and subsequent therapy for partial response, no response, relapsed, progressive or refractory disease in non-candidates for transplant (NCCN 2A).

2. Must be dosed in accordance with the FDA label.

B-Cell Lymphomas - High-Grade B-Cell Lymphomas

1. Used as a single agent or in combination with bendamustine and/or rituximab as second-line and subsequent therapy if no intention to proceed to transplant (NCCN 2A):

a. Relapsed or refactory disease >12 months after completion of first-line therapy.

b. Primary refractory disease or relapsed disease, 12 months after completion of first-line therapy if no intention to proceed to CAR T-cell therapy.

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy.

2. Used with or without bendamustine and with or without rituximab as clinically indicated as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease <12 months after completion of first line therapy. (NCCN 2A).

3. Must be dosed in accordance with the FDA label.

B-Cell Lymphomas - AIDS-Related B-Cell Lymphomas

1. Second-line and subsequent therapy as a single agent or in combination with bendamustine and/or rituximab for HIV-related diffuse large B-cell lymphoma, primary effusion lymphoma, and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified, or without rituximab for relapse of HIV-related plasmablastic lymphoma if no intention to proceed to transplant for (NCCN 2A):

a. Relapsed or refractory disease >12 months after completion of first-line therapy.

b. Primary refractory disease or relapsed disease <12 months after completion f first-line therapy if not intention ot proceed to CAR T-cell therapy.

c. Alternative systemic therapy for relapsed/refractory disease if no intention to proceed CAR T-cell therapy.

2. Used a single agent or in combination with bendamustine and/or rituximab as clinically indicated as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease <12 months after completion of first-line therapy.

3. Must be dosed in accordance with the FDA label.

B-Cell Lymphomas - Post-Transplant Lymphoproliferative Disorders

1. Second-line and subsequent therapy as a single agent or with bendamustine and/or rituximab for monomorphic PTLD if no intention to proceed to transplant (NCCN 2A):

a. For relapsed or refractory disease >12 months after completion of initial treatment with chemoimmunotherapy.

b. For primary refractory disease or relapsed disease <12 months after completion of initial treatment with chemoimmunotherapy if no intention to proceed to CAR T-cell therapy.

c. As alternative systemic therapy for relapsed/refractory disease if no intention ot proceed to CAR T-cell therapy.

2. Used as clinically indicated as a single agent or in combination with bendamustine and/or rituximab as a bridging option until CAR T-cell product is available for primary refractory disease or relapsed disease <12 months after completion of initial treatment with chemoimmunotherapy.

3. Must be dosed in accordance with the FDA label.

B-Cell Lymphomas – Histologic Transformation of Indolent Lymphomas to Diffuse Large B-Cell Lymphoma

1. Preferred as a single agent or in combination with bendamustine and/or rituximab if previously treated with an anthracycline-based regimen if no intention ot proceed to transplant. (NCCN 2A)

a. As additional therapy for partial response, no response, or progressive disease following chemoimmunotherapy if histologic transformation to diffuse large B-cell lymphoma after minimal or no prior treatment.

b. After multiple prior therapies for indolent or transformed disease.

2. Must be dosed in accordance with the FDA label.

Dosage and Administration

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.

Polatuzumab vedotin-piiq is available as injection: 30 mg or 140 mg as a lyophilized powder in a single-dose vial.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

Effective January 2022 to February 2023

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications when specified criteria are met:

B-Cell Lymphomas-Follicular Lymphoma

Used as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)as subsequent therapy for refractory or progressive disease in patients with indications for treatment (NCCN 2A).
Used as a single agent or in combination with bendamustine and/or rituximab for treatment of histologic transformation to diffuse large B-cell lymphoma (DLBCL) with translocations of MYC and BCL2 and/or BCL6 in patients who have received (NCCN 2A):

Minimal or no chemoimmunotherapy prior to histologic transformation to DLBCL and have no response or progressive disease after chemoimmunotherapy (anthracycline- or anthracenedione-based regimens preferred unless contraindicated); or
multiple prior therapies including 2 or more lines of chemoimmunotherapy for indolent or transformed disease.

B-Cell Lymphomas- Histologic Transformation of Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

Used as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)for patients who have received multiple prior therapies including 2 or more lines of chemoimmunotherapy for indolent or transformed disease (NCCN 2A).

B-Cell Lymphomas-Diffuse Large B-Cell Lymphoma

Preferred as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)as second-line and subsequent therapy for partial response, no response, relapsed, progressive or refractory disease in non-candidates for transplant (NCCN 2A).

B-Cell Lymphomas - High-Grade B-Cell Lymphomas with Translocations of MYC and BCL2 and/or BCL6 (Double/Triple Hit Lymphoma)

Used as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)as second-line and subsequent therapy for partial response, no response, relapsed, progressive or refractory disease in non-candidates for transplant (NCCN 2A).

B-Cell Lymphomas - High-Grade B-Cell Lymphomas, NOS

Used as a single agent or in combination with bendamustine and/or rituximab (including rituximab biosimilars)as second-line and subsequent therapy for partial response, no response, relapsed, progressive or refractory disease in non-candidates for transplant (NCCN 2A).

B-Cell Lymphomas - AIDS-Related B-Cell Lymphomas

Second-line and subsequent therapy as a single agent or in combination with bendamustine with rituximab (including rituximab biosimilars) for:

Relapse of AIDS-related diffuse large B-cell lymphoma (NCCN 2A);
Primary effusion lymphoma (NCCN 2A); or
HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (NOS).

Second-line and subsequent therapy as a single agent or in combination with bendamustine without rituximab (including rituximab biosimilars)for relapse of AIDS-related plasmablastic lymphoma in non-candidates for transplant (NCCN 2A).

B-Cell Lymphomas - Post-Transplant Lymphoproliferative Disorders

Subsequent therapy as a single agent or with bendamustine and/or rituximab (including rituximab biosimilars) for patients with partial response, persistent or progressive disease after receiving 2 or more lines of chemoimmunotherapy for monomorphic PTLD (B-cell type) (NCCN 2A).

Dosage and Administration

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

Effective June 2021 through December 31, 2021

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

A. Diagnosis of one of the following:

relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (including high-grade B-cell lymphomas); OR relapsed or refractory high-grade B-cell lymphoma with translocations of MYC and BCL2 and/or BCL6, OR
other types of B-cell lymphoma including follicular lymphoma, AIDS-related lymphomas, and B-Cell post-transplant lymphoproliferative disorders

AND

B. ALL of the below:

used as a single agent or in combination with bendamustine and a rituximab (including rituximab biosimilars), AND
member has received at least two prior therapies; AND
is ineligible for autologous hematopoietic stem cell transplantation (HSCT).

Dosage and Administration

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

The use of Polatuzumab vedotin-piiq does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

Rationale:

The efficacy of polatuzumab vedotin-piiq was evaluated in Study GO29365 (NCT02257567), an open-label, multicenter clinical trial that included a cohort of 80 individuals with relapsed or refractory DLBCL after least one prior regimen. Individuals were randomized 1:1 to receive either POLATUZUMAB VEDOTIN in combination with bendamustine and a rituximab product (BR) or BR alone for six 21-day cycles. Randomization was stratified by duration of response (DOR) to last therapy. Eligible individuals were not candidates for autologous HSCT at study entry. The study excluded individuals with Grade 2 or higher peripheral neuropathy, prior allogeneic HSCT, active central nervous system lymphoma, or transformed lymphoma. Polatuzumab vedotin-piiq was given by intravenous infusion at 1.8 mg/kg on Day 2 of Cycle 1 and on Day 1 of Cycles 2–6. Bendamustine was administered at 90 mg/m2 intravenously daily on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2–6. A rituximab product was administered at a dose of 375 mg/m2 intravenously on Day 1 of Cycles 1–6. The cycle length was 21 days.

Of the 80 individuals randomized to receive Polatuzumab vedotin-piiq plus BR (n = 40) or BR alone (n = 40), the median age was 69 years (range: 30–86 years), 66% were male, and 71% were white. Most individuals (98%) had DLBCL not otherwise specified. The primary reasons individuals were not candidates for HSCT included age (40%), insufficient response to salvage therapy (26%), and prior transplant failure (20%). The median number of prior therapies was 2 (range: 1–7), with 29% receiving one prior therapy, 25% receiving 2 prior therapies, and 46% receiving 3 or more prior therapies. Eighty percent of individuals had refractory disease to last therapy. In the Polatuzumab vedotin-piiq plus BR arm, of the 25 individuals who achieved a partial or complete response, 16 (64%) had a DOR of at least 6 months, and 12 (48%) had a DOR of at least 12 months. In the BR arm, of the 10 individuals who achieved a partial or complete response, 3 (30%) had a DOR lasting at least 6 months, and 2 (20%) had a DOR lasting at least 12 months.

The safety of Polatuzumab vedotin in combination with R-CHP (rituximab, cyclophosphamide, doxorubicin and prednisone) chemoimmunotherapy was evaluated in POLARIX, a randomized double-blind, placebo-controlled, multicenter study of 873 individuals with previously untreated large B-cell lymphoma, 435 of whom received polatuzumab vedotin plus R-CHP. Individuals were randomized 1:1 to receive polatuzumab vedotin plus R-CHP or to receive R-CHOP for six 21-day cycles followed by two additional cycles of rituximab alone in both arms. Granulocyte colony-stimulating factor (G-CSF) primary prophylaxis was required and administered to 90% of individuals in the polatuzumab vedotin plus R-CHP arm and 93% of individuals in the R-CHOP arm. Following premedication with an antihistamine and antipyretic, polatuzumab vedotin was administered intravenously at 1.8 mg/kg on Day 1 of Cycles 1–6. R-CHP was administered starting on Day 1 of Cycles 1–6. Rituximab monotherapy was administered on Day 1 of Cycles 7–8. The trial required an absolute neutrophil count ≥1,000/µL, platelet count ≥75,000/µL, creatinine clearance (CLcr) ≥40 mL/min, hepatic transaminases ≤2.5 times the upper limit of normal (ULN), and bilirubin 80, ECOG performance status above 2, known central nervous system (CNS) lymphoma, and Grade 2 or higher peripheral neuropathy. The median age was 65 years overall (range: 19 to 80 years); 54% of individuals were male; 53% were White, 19% were Asian, 2%, Black or African American, and 5% were Hispanic or Latino. In the polatuzumab vedotin plus R-CHP group, 92% of individuals received 6 cycles of polatuzumab vedotin, and 94% completed 6 cycles of combination therapy. Serious adverse reactions occurred in 34% of individuals who received polatuzumab vedotin plus R-CHP, including febrile neutropenia and pneumonia in ≥5% of recipients. Fatal adverse reactions occurred in 3% of recipients of polatuzumab vedotin plus R-CHP within 90 days of last treatment, primarily from infection including pneumonia (0.9%) and sepsis (0.2%). Adverse reactions led to dose reduction of polatuzumab vedotin in 6% of individuals, mainly from peripheral neuropathy. Adverse reactions lead to dose interruption of polatuzumab vedotin in 18% of individuals, most commonly from pneumonia and neutropenia, and permanent discontinuation of polatuzumab vedotin in 4.4% of individuals.

In a prespecified descriptive analysis of the largest lymphoma subgroup, DLBCL, NOS, the PFS HR was 0.75 (95% CI: 0.57, 0.99). In individuals with HGBL, the PFS HR was 0.48 (95% CI: 0.21, 1.08). There were insufficient data to evaluate efficacy in other large B-cell lymphomas. With an estimated median follow-up of 3.3 years, the prespecified final analysis of overall survival (OS) showed no statistically significant difference, with a HR of 0.94 (95% CI: 0.67, 1.33). In a descriptive analysis, the OS HR in individuals with DLBCL, NOS was 1.02 (95% CI: 0.70, 1.49). The OS HR in individuals with HGBL was 0.42 (95% CI: 0.15, 1.19).

2022 Update

Annual policy review completed with a literature search using the MEDLINE database through March 2022. No new literature was identified that would prompt a change in the coverage statement.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through March 2023. No new literature was identified that would prompt a change in the coverage statement.

2024 Update

Additional FDA-approved indication has been included in the coverage statement. Clinical criteria for off-label indications have been updated according to newest NCCN guidelines.

June 2024 Update

As described in Rojek et al (2022), the International Prognostic Index (IPI) for DLBCL was adjusted to better stratify prognosis in limited-stage disease by removing the number of extranodal sites and dichotomizing stage as I versus II. This stage-modified IPI (smIPI) thus includes one point each for age > 60 years, stage II disease, elevated serum lactate dehydrogenase (LDH), and performance status of two or above. In the pre-rituximab era, those with no risk factors, and thus stage I disease, had the best outcomes with 5-year overall survival (OS) of 95%; for those with one to two risk factors, 5-year OS dropped to 77%, and 50% for three or more risk factors. This smIPI model was more powerful than an age-adjusted risk stratification alone. In the rituximab era, outcomes in each IPI risk group have improved across both limited and advanced disease groups, and smIPI retains utility.

2025 Update

A double-blind, placebo-controlled, international phase 3 trial was conducted to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety.

Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups.

Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (ClinicalTrials.gov number, NCT03274492.). (Tilly, 2022)

CPT/HCPCS:

References:

Douglas M(2020) Polatuzumab Vedotin for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Transplant-Ineligible Patients, J Adv Pract Oncol Actions. 2020 Jul;11(5):521-528. doi: 10.6004/jadpro.2020.11.5.8. Epub 2020 Jul 1.

National Comprehensive Cancer Network (NCCNA)(2023) National Comprehensive Cancer Network, Inc. 2023 Practice Guidelines in Oncology v.1.2023. Available at https://www.nccn.org. Accessed March 8, 2023.

National Comprehensive Cancer Network(2021) Policy NCCN guidelines Accessed at https://www.nccn.org/professionals/drug_compendium/content/

Segman Y, Ribakovsky E, Avigdor A, et.al.,(2021) Outcome of relapsed/refractory diffuse large B-cell lymphoma patients treated with polatuzumab vedotin-based therapy: real-life experience, Leuk Lymphoma . 2021 Jan;62(1):118-24 doi10.1080/10428194.2020.1824069. Epub 2020 Sep 27.

Sehn L, Herrera A, Flowers C, et.al.,(2020) Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma, J Clin Oncol . 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.

Sehn LH, Herrera AF, Matasar MJ, et.al.,(2018) Polatuzumab vedotin (Pola) plus bendamustine (B) with rituximab (R) or obinutuzumab (G) in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Updated results of a phase (Ph) Ib/II study. Blood 2018;132(Suppl 1):1683. Available at: http://www.bloodjournal.org/content/132/Suppl_1/1683.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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