Medical Policy

Policy Num:       05.001.044
Policy Name:     Polivy® (polatuzumab vedotin-piiq)
Policy ID:          [05.001.044] [Ac / L / M+ / P+] [0.00.00]

Last Review:       October 24, 2024
Next Review:      October 20, 2025
 

Related Policies: None

 Polivy^® (polatuzumab vedotin-piiq)

Summary

POLIVY is a CD79b-directed antibody–drug conjugate indicated in combination with bendamustine and a rituximab product for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies

Objective

The objective of this evidence-based review is to determine wheather polatuzumab improves the net health outcome in patients with need of oncologic treatment.
 

Policy Statements

Polatuzumab vedotin-piiq (Polivy) is considered medically necessary for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) when the following criteria are met:

• The patient has relapsed or refractory disease; and

• Polatuzumab vedotin is administered in combination with bendamustine and a rituximab product; and

• The patient has received at least two prior systemic chemotherapies; and

• The patient is not a candidate for autologous hematopoietic stem cell transplantation (HSCT);

and

• The patient has not previously undergone allogeneic HSCT; and

• The patient does not have active central nervous system lymphoma or histologically transformed lymphoma.

Authorization: 12 months

Use of polatuzumab vedotin-piiq (Polivy) may be considered medically necessary for clinical indications not listed above when the drug is prescribed for the treatment of cancer either:

• In accordance with FDA label (when clinical benefit has been established, (see Policy

Guidelines); OR

• In accordance with specific strong endorsement or support by nationally recognized compendia, when such recommendation is based on strong/high levels of evidence, and/or uniform consensus of clinical appropriateness has been reached.

Policy Guidelines

Length of Authorization

Coverage will be provided for six months (up to 6 cycles of therapy) and may NOT be renewed.

II. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Polivy 140 mg SDV vial: 1 vial per 21 days*

B. Max Units (per dose and over time) [HCPCS Unit]:

• 140 billable units every 21 days*

III. Initial Approval Criteria 1

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria 1,3

• Patient will receive prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus;

AND

• Patient does not currently have Grade ≥ 2 peripheral neuropathy; AND

• Patient does not have CNS lymphoma; AND

B-Cell Lymphomas † ‡ 1,2,3,4

• Patient has diffuse large B-cell lymphoma (DLBCL)Ф; AND

o Patient has partial response, no response, relapsed, progressive or refractory disease;

AND

o Patient is not a candidate for stem cell transplant; AND

o Used in combination with bendamustine and rituximab; AND

o Used as subsequent treatment after at least two prior therapies

(**Note: For patients with relapsed disease who received prior bendamustine, response duration must

have been >1 year)

The recommended dose of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with bendamustine and rituximab product. Administer POLIVY, bendamustine, and rituximab product in any order on Day 1 of each cycle. The recommended dose of bendamustine is 90 mg/m2 /day on Day 1 and 2 when administered with POLIVY and a rituximab product. The recommended dose of rituximab product is 375 mg/m2 intravenously on Day 1 of each cycle. If not already premedicated, administer an antihistamine and antipyretic at least 30 minutes prior to POLIVY. Administer the initial dose of POLIVY over 90 minutes. Monitor patients for infusion-related reactions during the infusion and for a minimum of 90 minutes following completion of the initial dose. If the previous infusion was well tolerated, the subsequent dose of POLIVY may be administered as a 30-minute infusion and patients should be monitored during the infusion and for at least 30 minutes after completion of the infusion. If a planned dose of POLIVY is missed, administer as soon as possible. Adjust the schedule of administration to maintain a 21-day interval between doses.

The most common adverse reactions (≥20%) included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia

Benefit Application

BlueCard/National Account Issues - N/A

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered.  Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Diffuse large B cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 25 percent of NHL cases. In the United States and England, the incidence of DLBCL is approximately 7 cases per 100,000 persons per year and the incidence varies by ethnicity, with Caucasian Americans having higher rates than Blacks, Asians, and American Indian or Alaska Natives, in order of decreasing incidence. Like most other NHLs, there is a male predominance with approximately 55 percent of cases occurring in men. Incidence increases with age; the median age at presentation is 64 years for patients, with a younger age for Blacks than for Caucasian Americans. Although it can be cured, about 30 to 40% of patients suffer relapse. This type of cancer grows quickly in the lymph nodes and may affect the bone marrow, spleen, liver or other organs. Signs and symptoms of DLBCL may include swollen lymph nodes, fever, recurring night sweats and weight loss (Freedman, 2019; FDA,2019).

Polatuzumab vedotin-piiq is an antibody that is attached to a chemotherapy drug (antibody-drug conjugate). Polatuzumab binds to the CD79b protein found only on B cells, then releases the chemotherapy drug into those cells.

Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate (ADC) consisting of three components: 1) the humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for human CD79b; 2) the small molecule anti-mitotic agent MMAE; and 3) a protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB) that covalently attaches MMAE to the polatuzumab antibody.

Polatuzumab vedotin-piiq has an approximate molecular weight of 150 kDa. An average of 3.5 molecules of MMAE are attached to each antibody molecule. Polatuzumab vedotin-piiq isproduced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.

POLIVY (polatuzumab vedotin-piiq) for injection is supplied as a sterile, white to grayish-white, preservative-free, lyophilized powder, which has a cake-like appearance, for intravenous infusion after reconstitution and dilution. After reconstitution with 7.2 mL of Sterile Water for Injection, USP, the final concentration is 20 mg/mL with a pH of approximately 5.3. Each single-dose vial delivers 140 mg of polatuzumab vedotin-piiq, polysorbate-20 (8.4 mg), sodium hydroxide (3.80 mg), succinic acid (8.27 mg), sucrose (288 mg).

The POLIVY vial stoppers are not made with natural rubber latex.

Mechanism of Action

Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate with activity against dividing B cells. The small molecule, MMAE is an anti-mitotic agent covalently attached to the antibody via a cleavable linker. 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.

Regulatory Status

On June 10, 2019, The U.S. Food and Drug Administration (FDA) approved Polivy (polatuzumab vedotin-piiq), in combination with the chemotherapy bendamustine and a rituximab product (a combination known as “BR”), to treat adult patients with diffuse large B-cell lymphoma (DLBCL) that has progressed or returned after at least two prior therapies. Polatuzumab is a novel antibody-drug conjugate intended to target specific cells (FDA, 2019)

Rationale

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Relapsed or Refractory Diffuse Large B-cell Lymphoma

The efficacy of POLIVY was evaluated in Study GO29365 (NCT02257567), an open-label, multicenter clinical trial that included a cohort of 80 patients with relapsed or refractory DLBCL after least one prior regimen. Patients were randomized 1:1 to receive either POLIVY 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 patients were not candidates for autologous HSCT at study entry. The study excluded patients with Grade 2 or higher peripheral neuropathy, prior allogeneic HSCT, active central nervous system lymphoma, or transformed lymphoma.

Following premedication with an antihistamine and antipyretic, POLIVY 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 patients randomized to receive POLIVY 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 patients (98%) had DLBCL not otherwise specified. The primary reasons patients 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 patients had refractory disease to last therapy.

In the POLIVY plus BR arm, patients received a median of 5 cycles, with 49% receiving 6 cycles. In the BR arm, patients received a median of 3 cycles, with 23% receiving 6 cycles. Efficacy was based on complete response (CR) rate at the end of treatment and DOR, as determined by an independent review committee (IRC). Other efficacy measures included IRCassessed best overall response.

In the POLIVY plus BR arm, of the 25 patients 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 patients 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.

Tilly et al (2019; NCT01992653) stated polatuzumab vedotin, an antibody-drug conjugate targeting the CD79b component of the B-cell receptor, has demonstrated activity as a single agent and in combination with rituximab in relapsed or refractory diffuse large B-cell lymphoma. In this study, the authors evaluated the safety and preliminary activity of polatuzumab vedotin in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, and prednisone (CHP) in patients with previously untreated diffuse large B-cell lymphoma. This was an open-label, non-randomized study composed of a phase 1b dose escalation and a phase 2 dose expansion at 11 hospitals and health centers in the USA and France. Patients aged 18 years or older with B-cell non-Hodgkin lymphoma were eligible. Exclusion criteria included peripheral neuropathy with grade greater than 1, major surgery within 4 weeks before enrolment, known CNS involvement of lymphoma, and uncontrolled heart disease. Phase 1b dose escalation had a three-plus-three design and established the recommended phase 2 dose. Phase 2 expansion evaluated the recommended phase 2 dose of polatuzumab vedotin in patients with newly diagnosed diffuse large B-cell lymphoma with an International Prognostic Index (IPI) of 2-5. Patients received cyclophosphamide 750 mg/m2 on day 1 intravenously, doxorubicin 50 mg/m2 on day 1 intravenously, and prednisone 100 mg once daily on days 1-5 of each 21-day cycle orally (CHP), plus either rituximab 375 mg/m2 intravenously on day 1 of each cycle (R-CHP) or obinutuzumab 1000 mg intravenously on days 1, 8, and 15 of cycle 1 and on day 1 of the following cycles (G-CHP). Polatuzumab vedotin was administered on day 2 of cycles 1 and 2, and on day 1 of the following cycles at 1·0-2·4 mg/kg during the escalation phase and at the recommended phase 2 dose during the expansion phase. Treatment could last six or eight cycles, depending on investigator preference. The primary endpoints of the study were safety and tolerability, and determination of the maximum tolerated dose (or recommended phase 2 dose) of polatuzumab vedotin. All endpoints were analyzed per protocol in the safety evaluable population, defined as all patients who received at least one dose of study treatment. Between Dec 4, 2013, and July 26, 2016, 85 patients were enrolled. 82 patients were included in the safety and activity evaluable populations, 25 in phase 1b and 57 in phase 2. In light of information from other studies using polatuzumab vedotin reported during this study, in which the safety profile associated with exposure to polatuzumab vedotin at doses higher than 1·8 mg/kg every 3 weeks was not outweighed by any clinical benefit, the recommended phase 2 dose was set to 1·8 mg/kg in the R-CHP cohort and no higher doses were explored in this study. 66 patients with newly diagnosed diffuse large B-cell lymphoma received the polatuzumab vedotin recommended phase 2 dose (45 R-CHP; 21 G-CHP). In 66 patients with diffuse large B-cell lymphoma who received the recommended phase 2 dose, the most common adverse events of grade 3 or worse were neutropenia (20 [30%]), febrile neutropenia (12 [18%]), and thrombocytopenia (six [9%]). Among the 70 patients (any histology) who received the recommended phase 2 dose, 19 (27%) had grade 1 peripheral neuropathy, eight (11%) grade 2, and two (3%) grade 3. Four deaths were reported during follow-up: two treatment-related (one complication of atrial fibrillation and one septic shock) and two deaths were due to disease progression. As of the cutoff date of Dec 29, 2017, median follow-up time was 21·5 months (IQR 16·7-24·3) for the untreated diffuse large B-cell lymphoma cohort treated at the polatuzumab vedotin recommended phase 2 dose. 59 (89%) patients achieved an overall response at end of treatment (51 [77%] patients had a complete response, and eight [12%] patients had a partial response). The safety of incorporating polatuzumab vedotin to R-CHP or G-CHP was as expected and manageable. Preliminary clinical activity in newly diagnosed diffuse large B-cell lymphoma seems promising and encouraged a phase 3 trial comparing polatuzumab vedotin with R-CHP to R-CHOP (Tilly, 2019).

Morschhauser et al (2019; NCT01691898) stated antibody-drug conjugates (ADCs) polatuzumab vedotin (pola) and pinatuzumab vedotin (pina) showed clinical activity and tolerability in phase 1 trials. The aim of this multicenter, open-label, phase 2 study was to compare rituximab plus pola (R-pola) or pina (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. In this phase 2 randomized study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomization scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs) every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumor response. The study is closed to accrual. 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI: 43-74) achieved an objective response and 11 (26%, 95% CI: 14-42) achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI: 37-70) achieved an objective response, and eight (21%, 95% CI: 9-36) achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI: 38-82) achieved an objective response, and one (5%, 95% CI: 0·1-24) achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI: 46-88) achieved an objective response, and nine (45%, 95% CI: 23-68) achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3-5 adverse events occurred in 33 (79%) of 42 patients receiving R-pina (most common were neutropenia [29%] and hyperglycemia [10%]; nine [21%] grade 5 adverse events, five of which were infection-related), and in 30 (77%) of 39 patients receiving R-pola (most common were neutropenia [23%], anemia [8%] and diarrhea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3-5 adverse events occurred in 13 (62%) of 21 patients receiving R-pina (most common were neutropenia [29%] and hyperglycemia [14%]; no grade 5 adverse events) and in ten (50%) of 20 patients receiving R-pola (most common were neutropenia [15%] and diarrhea [10%]; one grade 5 adverse event). The authors concluded that R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit-risk favoring R-pola (Morschhauser, 2019).

Population Reference No. 1 

Diffuse Large B-Cell Lymphoma -FDA Indication

For the treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL)

When ALL of the following criteria are met:

Given in combination with bendamustine and a rituximab product; and

Documentation of diagnosis of DLBCL; and

Documentation of at least two (2) prior therapies; and

Administration of prophylaxis forPneumocystis jirovecipneumonia and herpes virus throughout treatment with polatuzumab vedotin (Polivy).

Population Reference No. 2 

As subsequent therapy, after at least 2 prior therapies, as a single agent or in combination with bendamustine with or without a rituximab product for relapse of ANY of the following:

AIDS-related DLBCL; or

Primary effusion pneumonia; or

HHV8-positive DLBCL, not otherwise specified; or

Without rituximab for relapse of AIDS-related plasmablastic lymphoma in non-candidates for transplant

Population Reference No. 3 

Diffuse Large B-Cell Lymphoma OFF Label - NCCN Recommendation

As a single agent or in combination with bendamustine and/or a rituximab product as subsequent therapy for partial response, no response, relapsed, progressive, or refractory disease after at least 2 prior therapies in non-candidates for transplant

Population Reference No. 4 

Folicular Lymphoma (Grade 1-2( OFF LABEL - NCCN Recommendation

As a single agent or in combination with bendamustine and/or a rituximab product for treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received EITHER:

Minimal or no chemoimmunotherapy prior to histologic transformation to DLBCL and have no response or progressive disease after chemoimmunotherapy (anthracycline or anthracenedione-based regimens, unless contraindicated); or

Multiple prior therapies including at least 2 lines of chemoimmunotherapy for indolent or transformed disease; or

As a single agent or in combination with bendamustine and/or a rituximab product as subsequent therapy after at least 2 prior therapies for refractory or progressive disease in individuals with indications for treatment

Population Reference No. 5 

High-Grade B- Cell Lymphomas OFF LABEL – NCCN Recommendation

As a single agent or in combination with bendamustine and/or a rituximab product as second-line and subsequent therapy for partial response, no response, relapsed, progressive, or refractory disease after at least 2 prior therapies in non-candidates for transplant;

Population Reference No. 6 

Histologic Transformation of Nodal Marginal Zone to Diffuse Large B-Cell Lymphoma OFF LABEL – NCCN Recommendation

As a single agent or in combination with bendamustine and/or a rituximab product for individuals who have received multiple prior therapies including at least 2 lines of chemoimmunotherapy for indolent or transformed disease.

Population Reference No. 7 

Mantle Cell Lymphoma OFF LABEL – NCCN Recommendation

As subsequent therapy after at least 2 prior therapies as a single agent or in combination with bendamustine and/or a rituximab product for stage I-II, aggressive stage II bulky, III, or IV, or symptomatic indolent stage II bulky, III, or IV disease in individuals who have stable disease or partial response with substantial disease after induction therapy, or who have relapsed or progressive disease

Population Reference No. 8 

Post-Transplant Lymphoproliferative Disorder OFF LABEL – NCCN Recommendation

As subsequent therapy as a single agent or with bendamustine and/or a rituximab product for individuals with a partial response, persistent or progressive disease after receiving at least 2 lines of chemoimmunotherapy for monomorphic post-transplant lymphoproliferative disorder

Population Reference No. 9

B-Cell Lymphomas - Diffuse Large B-Cell Lymphoma-Histologic Transformation of Indolent Lymphomas to Diffuse Large B-Cell Lymphoma-High-Grade B-Cell Lymphomas-- HIV-Related B-Cell Lymphomas-Post-Transplant Lymphoproliferative Disorders

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
relapsed disease >12 months after completion of first-line therapy
primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy in non-candidates for CAR T-cell therapy
alternative systemic therapy (if not previously used) for relapsed/refractory disease in non-candidates for CAR T-cell therapy
Used with or without bendamustine and with or without rituximab (consider/add bendamustine only after leukapheresis) 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
Preferred as a single agent or in combination with bendamustine and/or rituximab if previously treated with an anthracycline-based regimen and no intention to proceed to transplant
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
for histologic transformation of follicular or marginal zone lymphomas after multiple lines of prior therapies including ≥2 chemoimmunotherapy regimens for indolent or transformed disease
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
relapsed disease >12 months after completion of first-line therapy
primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy in non-candidates for CAR T-cell therapy
alternative systemic therapy (if not previously used) for relapsed/refractory disease in non-candidates for CAR T-cell therapy
Used with or without bendamustine and with or without rituximab (consider/add bendamustine only after leukapheresis) 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
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
relapsed disease >12 months after completion of first-line therapy
primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy in non-candidates for CAR T-cell therapy
alternative systemic therapy (if not previously used) for relapsed/refractory disease in non-candidates for CAR T-cell therapy
Used as a single agent or in combination with bendamustine and/or rituximab (consider/add bendamustine only after leukapheresis) 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

Supplemental Information

N/A

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Recommendations

The NCCN Drugs and Biologics Compendium (NCCN, 2020) recommends polatuzumab for the following: 

B-Cell Lymphomas 

·         High-Grade B-Cell Lymphomas - Used as a single agent or in combination with bendamustine and/or rituximab as second-line or subsequent therapy for partial response, no response, relapsed, progressive or refractory disease after ≥2 prior therapies in non-candidates for transplant [2A]

·         Follicular Lymphoma (grade 1-2) - 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) without translocations of MYC and BCL2 and/or BCL6 in patients who have received [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) 

·         multiple prior therapies including ≥2 lines of chemoimmunotherapy for indolent or transformed disease

·         Follicular Lymphoma (grade 1-2) - Used as a single agent or in combination with bendamustine and/or rituximab as subsequent therapy (after ≥2 prior therapies) for refractory or progressive disease in patients with indications for treatment [2A]

·         Mantle Cell Lymphoma - Subsequent therapy (after ≥2 prior therapies) as a single agent or in combination with bendamustine and/or rituximab for stage I-II, aggressive stage II bulky, III, or IV, or symptomatic indolent stage II bulky, III, or IV disease in patients who have stable disease or partial response with substantial disease after induction therapy, or who have relapsed or progressive disease [2A]

·         Post-Transplant Lymphoproliferative Disorders - Subsequent therapy as a single agent or with bendamustine and/or rituximab for patients with partial response, persistent or progressive disease after receiving ≥2 lines of chemoimmunotherapy for monomorphic PTLD (B-cell type) [2A]

·         AIDS-Related B-Cell Lymphomas - Subsequent therapy (after ≥2 prior therapies) as a single agent or in combination with bendamustine with or without rituximab for relapse of AIDS-related diffuse large B-cell lymphoma, primary effusion lymphoma, and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (NOS) or without rituximab for relapse of AIDS-related plasmablastic lymphoma in non-candidates for transplant [2A]

·         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 for patients who have received multiple prior therapies including ≥2 lines of chemoimmunotherapy for indolent or transformed disease [2A]

·         Diffuse Large B-Cell Lymphoma - Preferred as a single agent or in combination with bendamustine and/or rituximab as second-line or subsequent therapy for partial response, no response, relapsed, progressive or refractory disease after ≥2 prior therapies in non-candidates for transplant [2A]

Medicare National Coverage

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual

(Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage

Determination (NCD), Local Coverage Articles (LCAs) and Local Coverage Determinations (LCDs)

may exist and compliance with these policies is required where applicable. They can be found at:

http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional

indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD): N/A

References

1.    Freedman AS and Aster AC. Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed May 2019.

2.    Genentech, Inc. Polivy (polatuzumab) injection, for intravenous use. Prescribing Information. South San Francisco, CA: Genentech; June 2019.

3.    Morschhauser F, Flinn IW, Advani R, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019 May;6(5): e254-e265.

4.    National Comprehensive Cancer Network (NCCN). B-cell lymphomas. NCCN Clinical Practice Guidelines in Oncology, Version 4.2019. Fort Washington, PA: NCCN; 2019.

5.    National Comprehensive Cancer Network (NCCN). B-cell lymphomas. NCCN Clinical Practice Guidelines in Oncology, Version 4.2019. Fort Washington, PA: NCCN; 2020.

6.    National Comprehensive Cancer Network (NCCN). Polatuzumab. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; 2019.

7.    National Comprehensive Cancer Network (NCCN). Polatuzumab. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; 2020.

8.    Shemesh CS, Agarwal P, Lu T, et al. Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Mar 28 [Epub ahead of print].

9.    Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019;20(7):998-1010.

10. U.S. Food and Drug Administration (FDA). FDA approves first chemoimmunotherapy regimen for patients with relapsed or refractory diffuse large B-cell lymphoma. FDA News Release. Silver Spring, MD: FDA; June 10, 2019.

Codes

Applicable Modifiers

Policy History