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This is a new policy published on 8/27/2019. It will be effective on 9/28/2019 or later.
  
Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:195
Effective Date: 09/28/2019
Original Policy Date:08/27/2019
Last Review Date:
Date Published to Web: 08/27/2019
Subject:
Polatuzumab vedotin-piiq (Polivy)

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

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Polivy (polatuzumab vedotin-piiq) 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.

Polivy (polatuzumab vedotin-piiq) is an antibody that is attached to a chemotherapy drug. Polivy (polatuzumab vedotin-piiq) binds to a specific protein, CD79b found only on B cells, then releases the chemotherapy drug into those cells. The efficacy of Polivy (polatuzumab vedotin-piiq) was evaluated in 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 (polatuzumab vedotin-piiq) 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 (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 patients randomized to receive Polivy (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 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 (polatuzumab vedotin-piiq) 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 IRC assessed best overall response. Complete response rate was 40% with Polivy (polatuzumab vedotin-piiq) plus BR compared to 18% with BR alone. In the Polivy (polatuzumab vedotin-piiq) 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.

The most common side effects of Polivy (polatuzumab vedotin-piiq) plus BR include neutropenia,thrombocytopenia and anemia; peripheral neuropathy; fatigue; diarrhea; fever; decreased appetite; and pneumonia.

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.


Policy:
I. Polivy (polatuzumab vedotin-piiq) is medically necessary for the treatment for the treatment of adult members with relapsed or refractory diffuse large B-cell lymphoma when all of the following criteria are met:

      a. Member has failed ≥2 prior therapies AND

      [INFORMATIONAL NOTE: Patients in the clinical trial were not restricted to having tried specific prior therapies. Majority of the patients received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Other examples of therapies included either CVP (cyclophosphamide, vincristine, prednisone) or ICE (ifosfamide, carboplatin, etoposide) or EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) or GEMOX (gemcitabine,oxaliplatin) regimen or lenalidomide etc.

      As per NCCN (National Comprehensive Cancer Network) guidelines (Version 4.2019) on Diffuse Large B-Cell Lymphoma:

          First line therapy
          CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab with RT
          Dose-dense CHOP 14-rituximab

          Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)+ rituximab

          First line therapy for patients with poor left ventricular function
          CDOP (cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) + rituximab
          RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone)
          RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)

          First line for elderly patients (age <80 years)
          R-mini- CHOP

          Second line subsequent therapy
          Bendamustine +/- rituximab
          Bendamustine, rituximab and polatuzumab vedotin-piiq
          Brentuximab vedotin
          CAR T-Cell therapy
          CEPP (cyclophosphamide, etoposide, prednisone, procarbazine) +/- rituximab
          DHAP (dexamethasone, cisplatin, cytarabine) +/- rituximab
          DHAX (dexamethasone, cytarabine, oxaliplatin) +/- rituximab
          EPOCH + rituximab
          ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) +/- rituximab
          GDP gemcitabine dexamethasone, cisplatin, or carboplatin) +/- rituximab
          GemOX (gemcitabine,oxaliplatin) +/- rituximab
          Gemcitabine, vinorelbine, rituximab
          Ibrutinib
          ICE (ifosfamide, carboplatin, etoposide) +/- rituximab
          Lenalidomide +/- rituximab]
      b. Member will use in combination with bendamustine and a rituximab product AND

      c. Member will receive prophylaxis for pneumocystis jiroveci pneumonia and herpes virus throughout treatment AND

      d. Member has an ECOG performance ≤ 2

II. When Polivy (polatuzumab vedotin-piiq) is considered medically necessary, therapy will be approved for 6 cycles based on FDA-approved labeling:
      a. 1.8 mg/kg administered intravenously, given on Day 1 of each cycle of 21 days in duration for 6 cycles in combination with bendamustine and rituximab product
III. Use of Polivy (polatuzumab vedotin-piiq) for greater than 6 cycles is considered investigational.

[INFORMATIONAL NOTE: Based on the dosing section of the FDA labeled package insert:

Table 1 Management of Peripheral Neuropathy, Infusion-Related Reaction, and Myelosuppression
EventDose Modification
Grade 2–3 Peripheral
Neuropathy
Hold Polivy dosing until improvement to Grade 1 or lower.
If recovered to Grade 1 or lower on or before Day 14, restart Polivy with
the next cycle at a permanently reduced dose of 1.4 mg/kg.
If a prior dose reduction to 1.4 mg/kg has occurred, discontinue Polivy.
If not recovered to Grade 1 or lower on or before Day 14, discontinue
Polivy.
Grade 4 Peripheral
Neuropathy
Discontinue Polivy.
Grade 1–3 Infusion-Related
Reaction
Interrupt Polivy infusion and give supportive treatment.
For the first instance of Grade 3 wheezing, bronchospasm, or generalized
urticaria, permanently discontinue Polivy. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue Polivy. Otherwise, upon complete resolution of symptoms, infusion may be
resumed at 50% of the rate achieved prior to interruption. In the absence
of infusion related symptoms, the rate of infusion may be escalated in
increments of 50 mg/hour every 30 minutes. For the next cycle, infuse Polivy over 90 minutes. If no infusionrelated reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
Grade 4 Infusion-Related
Reaction
Stop Polivy infusion immediately. Give supportive treatment.
Permanently discontinue Polivy
Grade 3–4 Neutropeniaa,bHold all treatment until ANC recovers to greater than 1000/microliter.
If ANC recovers to greater than 1000/microliter on or before Day 7, resume
all treatment without any additional dose reductions. Consider granulocyte
colony stimulating factor prophylaxis for subsequent cycles, if not
previously given.
If ANC recovers to greater than 1000/microliter after Day 7:
      • restart all treatment. Consider granulocyte colony stimulating factor
      prophylaxis for subsequent cycles, if not previously given. If
      prophylaxis was given, consider dose reduction of bendamustine.
      • if dose reduction of bendamustine has already occurred, consider
      dose reduction of Polivy to 1.4 mg/kg
Grade 3–4
Thrombocytopeniaa,b
Hold all treatment until platelets recover to greater than 75,000/microliter.
If platelets recover to greater than 75,000/microliter on or before Day 7,
resume all treatment without any additional dose reductions.
If platelets recover to greater than 75,000/microliter after Day 7:
      • restart all treatment, with dose reduction of bendamustine.
      • if dose reduction of bendamustine has already occurred, consider dose reduction of Polivy to 1.4 mg/kg.
a Severity on Day 1 of any cycle.
b If primary cause is due to lymphoma, dose delay or reduction may not be needed.]

IV. Polivy (polatuzumab vedotin-piiq) is considered medically necessary for the following off-label uses:


    a. High-Grade B Cell Lymphoma
        i. Used in combination with bendamustine and 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
V. Other uses of Polivy (polatuzumab vedotin-piiq) are considered investigational, including but not limited to, follicular lymphoma.

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Polatuzumab vedotin-piiq (Polivy)
Polivy (Polatuzumab vedotin-piiq)

References:
1. Polivy [package insert]. Genentech, Inc.; South San Francisco, CA. June 2019.

2. Polivy [Dossier]. Genentech, Inc. South San Francisco, CA. July 2019.

3. Clinicaltrials.gov. Polivy. Available at [https://clinicaltrials.gov/ct2/show/NCT02257567]

4. NCCN Drugs and Biologics Compendium™. Polivy. 2019. [Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=399 <http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=399> ][ cited June 2019]

5. NCCN Guidelines Version 4.2019. Diffuse Large B-Cell Lymphoma. 2019. [Available at https://www.nccn.org/professionals/physician_gls/pdf/b-cell_blocks.pdf] Accessed August 6, 2019.

    Codes:
    (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

    CPT*
      HCPCS

      * CPT only copyright 2019 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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      Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

      The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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