Cigna National Formulary Coverage Policy

Prior Authorization Oncology – Copiktra™ (duvelisib capsules)

Table of Contents Product Identifier(s)

National Formulary Medical Necessity ...... 1 61689 Conditions Not Covered...... 2 Background ...... 2 References ...... 3 Revision History ...... 3

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

National Formulary Medical Necessity

Cigna covers duvelisib capsules (Copiktra™) as medically necessary when the following criteria are met for FDA Indications or Other Uses with Supportive Evidence:

Prior Authorization is recommended for prescription benefit coverage of Copiktra. All approvals are provided for the duration noted below.

FDA Indication(s)

1. Chronic Lymphocytic Leukemia (CLL). Approve for 3 years if the individual has tried two prior therapies. Note: Examples of therapies include Imbruvica® (ibrutinib capsules and tablets); Venclexta® ( tablets) with or without ; Venclexta plus Gazyva® (obinutuzumab injection for intravenous use); plus Gazyva; chlorambucil plus rituximab; FCR (, , and rituximab); FR (fludarabine plus rituximab); PCR (, cyclophosphamide, and rituximab); Treanda® ( injection) with or without rituximab; high-dose methylprednisolone (HDMP) plus rituximab; Campath® (alemtuzumab injection for intravenous use) with or without rituximab; Calquence® (acalabrutinib

Page 1 of 3 Cigna National Formulary Coverage Policy: PA Oncology – Copiktra capsules); Zydelig® ( tablets) with or without rituximab; Gazyva; Rituxan; Arzerra® (ofatumumab injection for intravenous use); or chlorambucil.

2. . Approve for 3 years if the individual has tried two prior therapies. Note: Examples of therapies include Treanda® (bendamustine injection) plus rituximab; Treanda plus Gazyva® (obinutuzumab injection for intravenous use); CHOP (cyclophosphamide, , , prednisone) plus Gazyva; RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone); RCVP (rituximab, cyclophosphamide, vincristine, prednisone); chlorambucil with or without rituximab; cyclophosphamide with or without rituximab; Gazyva; Revlimid® (lenalidomide capsules); CVP plus Gazyva; Zydelig® (idelalisib tablets); chlorambucil; cyclophosphamide; or Aliqopa® (copanlisib injection for intravenous use).

3. Small Lymphocytic Lymphoma (SLL). Approve for 3 years if the individual has tried two prior therapies. Note: Examples of therapies include Imbruvica® (ibrutinib capsules and tablets); Venclexta® (venetoclax tablets) with or without rituximab; Venclexta plus Gazyva® (obinutuzumab injection for intravenous use); chlorambucil plus Gazyva® (obinutuzumab injection for intravenous use); chlorambucil plus rituximab; FCR (fludarabine, cyclophosphamide, and rituximab); FR (fludarabine plus rituximab); PCR (pentostatin, cyclophosphamide, and rituximab); Treanda® (bendamustine injection) with or without rituximab; high-dose methylprednisolone (HDMP) plus rituximab; Campath® (alemtuzumab injection for intravenous use) with or without rituximab; Calquence® (acalabrutinib capsules); Zydelig® (idelalisib tablets) with or without rituximab; Gazyva; Rituxan; Arzerra® (ofatumumab injection for intravenous use); or chlorambucil.

Other Uses with Supportive Evidence

4. MALT Lymphoma (Gastric and Nongastric). Approve for 3 years if the individual has tried two other therapies. Note: Examples of therapies include rituximab; Treanda® (bendamustine injection for intravenous use) plus rituximab; RCHOP (rituximab, cyclophosphamide, vincristine, prednisone); RCVP (rituximab, cyclophosphamide, vincristine, prednisone); chlorambucil with or without rituximab; cyclophosphamide with or without rituximab; Imbruvica® (ibrutinib tablets and capsules); Zydelig® (idelalisib tablets); Revlimid® (lenalidomide capsules) with or without rituximab; or Aliqopa® (copanlisib injection for intravenous use).

5. Marginal Zone Lymphoma. Approve for 3 years if the individual has tried two other therapies. Note: Examples of therapies include rituximab; Treanda® (bendamustine injection for intravenous use) plus rituximab; RCHOP (rituximab, cyclophosphamide, vincristine, prednisone); RCVP (rituximab, cyclophosphamide, vincristine, prednisone); chlorambucil with or without rituximab; cyclophosphamide with or without rituximab; Imbruvica® (ibrutinib tablets and capsules); Zydelig® (idelalisib tablets); Revlimid® (lenalidomide capsules) with or without rituximab; or Aliqopa® (copanlisib injection for intravenous use).

Conditions Not Covered

Duvelisib capsules (Copiktra™) is considered experimental, investigational or unproven for ANY other use.

Background

Overview Copiktra, a kinase inhibitor, is indicated for the treatment of adults with:1 • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), relapsed or refractory, after at least two prior therapies. • Follicular lymphoma, relapsed or refractory, after at least two prior systemic therapies.

Disease Overview CLL is one of the most prevalent adult leukemias in the Western world, with an age-adjusted incidence of 4 to 5 per 100,000.2,3 In 2019, an estimated 20,720 patients were diagnosed with CLL in the US, and around 3,930 patients will die from the disease.3 The median age at diagnosis is 72 years of age and men are more affected

Page 2 of 3 Cigna National Formulary Coverage Policy: PA Oncology – Copiktra than women (2:1).2 Lymphadenopathy may be a finding upon presentation, as well as symptoms such as fevers, night sweat, weight loss, or fatigue.2,3 CLL and SLL are different manifestations of the same condition but managed similarily.3 Both diseases are characterized by a progressive accumulation of leukemic cells, which appear as small mature lymphocytes and may be found among occasional larger or atypical cells, in the peripheral blood, bone marrow, and lymphoid tissues. One major distinction is that in CLL, a significant number of the abnormal lymphocytes are present in blood, in addition to bone marrow and lymphoid tissue. Comparably, in SLL there are few, if any, abnormal lymphocytes circulating in blood. The bulk of the disease is in the lymph nodes, bone marrow, and in other lymphoid tissue. Many patients with CLL have cytogenetic abnormalities which can serve as markers that provide prognostic information. Drug therapy for CLL is not curative and is often not necessary in uncomplicated early disease. Some patients can be monitored without therapy until they have progressive or symptomatic/active disease. Many medications and therapy regimens are used to manage CLL. Factors to consider for recommending the most optimal regimen for a patient include disease stage, patient symptoms, fitness and other concomitant illnesses of the patient, genetic factors, and the treatment scenario.

Guidelines Copiktra is included in several guidelines published by the National Comprehensive Cancer Network (NCCN). • CLL/SLL: The NCCN guidelines for CLL/SLL (version 1.2021 – September 28, 2020) address CLL.3 Copiktra is one of several therapies for relapsed or refractory therapy (category 2A). The guidelines note that CLL and SLL are different manifestations of the same condition and are treated similarly. • Follicular Lymphoma: The NCCN guidelines for B-cell Lymphomas (version 4.2020 – August 13, 2020) recommend Copiktra as second-line and subsequent therapy in patients with follicular lymphoma (Grade 1 to 2) among patients relapsed or refractory after two prior therapies (category 2A).4 • Marginal Zone Lymphoma: The NCCN guidelines for B-Cell Lymphomas (version 4.2020 – August 13, 2020) recommend Copiktra as second-line and subsequent therapy for marginal zone lymphomas that are refractory or refractory to two prior therapies.4 Other regimens are recommended first-line including many that are rituximab-based. Many recommendations for the different types of gastric MALT and nongastric MALT lymphoma follow those of marginal zone lymphomas.

Safety Copiktra has a Boxed Warning regarding fatal and serious toxicities such as , diarrhea or colitis, cutaneous reactions, and pneumonitis.1 Copiktra was approved with a Risk Evaluation and Mitigation Strategy (REMS) program to assist physicians in the management of these risks. Other Warnings are present regarding hepatotoxicity, neutropenia, and embryofetal toxicity. References

1. Copiktra® capsules [prescribing information]. Needham, MA: Verastem; July 2019. 2. Hallek M, Shanafelt TD, Eichhorst B. Chronic lymphocytic leukemia. Lancet. 2018;391:1524-1537. 3. The NCCN Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Clinical Practice Guidelines in Oncology (Version 1.2021 − September 28, 2020). © 2020 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed on October 28, 2020. 4. The NCCN B-Cell Lymphomas Clinical Practice Guidelines in Oncology (Version 4.2020 − August 13, 2020). © 2020 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed on October 28, 2020. Revision History

Type of Summary of Changes Approval Date Revision Annual No criteria changes. 11/04/2020 Revision

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Page 3 of 3 Cigna National Formulary Coverage Policy: PA Oncology – Copiktra