Medical Policy

 

Subject: Copanlisib (Aliqopa®)
Document #: DRUG.00118 Publish Date:    12/12/2018
Status: Reviewed Last Review Date:    11/08/2018

Description/Scope

 

This document addresses the use of copanlisib (Aliqopa) (Bayer HealthCare Pharmaceuticals, Whippany, NJ), a P13K kinase inhibitor administered intravenously for the treatment of follicular lymphoma.

 

Position Statement

Medically Necessary:

Use of copanlisib is considered medically necessary for the treatment of adults older than 18 years of age with relapsed follicular lymphoma who have received at least two prior systemic therapies and have not had previous treatment with another PI3-kinase inhibitor previously (for example, idelalisib [Zydelig]).

Continuation of treatment with copanlisib is considered medically necessary as long as there is objective evidence of continuing clinical benefit (for example, complete response, partial response, or stable disease) verified at least every 6 months that is objectively measured.

Investigational and Not Medically Necessary:

Use of copanlisib is considered investigational and medically necessary for all other indications, including but not limited to when the criteria above have not been met.

Repeat treatment with copanlisib is considered investigational and medically necessary after the development of disease progression or unacceptable toxicity.

Rationale

Copanlisib (Aliqopa) was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on September 14, 2017. The approved indication was for the treatment of adult patients with follicular lymphoma who have relapsed after trying at least two systemic therapies.

Approval was based on data from a single-arm phase II multicenter clinical trial (NCT 01660451/CHRONOS-1) of 142 subjects, including 104 with follicular B-cell non-Hodgkin lymphoma who had relapsed disease after at least two prior treatments. The most common prior systemic therapies were chemotherapy in combination with anti-CD20 immunotherapy (89%), chemotherapy alone (41%), and anti-CD20 immunotherapy alone (37%). Subjects were treated with a fixed dose of 60 mg of copanlisib intravenously on days 1, 8, and 15 of a 28-day cycle, with treatment continued until disease progression or unacceptable toxicity. The median time to response was 1.7 months (range 1.3 to 9.7 months), with the following outcome reported:  Overall response rate (ORR) of 59% (n=61; 95% confidence interval [CI], 49, 68); complete response (CR) of 14% (n=15), and partial response (PR) of 44% (n=46). The median duration of response was 12.2 months.

In an earlier publication of the same clinical trial, Dreyling, et al. reported on 84 subjects with follicular B-cell non-Hodgkin lymphoma who underwent treatment with copanlisib following relapse disease after at least two prior systemic treatments (Dreyling, 2017). Of the 84 subjects included in the primary analysis, 33 had indolent lymphoma and 51 had aggressive lymphoma. An additional 17 subjects with aggressive lymphoma were enrolled in an expansion cohort. The most common histologic subtypes included follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%). Prior treatment with rituximab was reported in 78.6% of subjects, with 54.8% classified as rituximab-refractory. The median duration of treatment was 23 weeks and 8 weeks in the indolent and aggressive groups, respectively. The per-protocol primary efficacy analysis included 66 subjects, and the overall response rate (ORR) was 43.8% in the indolent cohort and 29.4% in the aggressive group. Additional analysis demonstrated that, per investigator assessment, 66.7% in the indolent group and 42.5% in the aggressive group had a reduction in lesion size of at least 50%.  In subjects with follicular lymphoma, complete response and unconfirmed complete response were observed in 3 of 15 subjects (20.0%) and partial response in an additional 3 subjects (20.0%).  The ORR was reported to be 40% in this group.  In the 15 subjects with chronic leukocytic leukemia, partial response was reported in 5 (ORR=38.5%). There were 3 subjects with marginal zone lymphoma, and 2 had partial response (ORR=66.7%).  Finally, partial response was reported in a single subject with small lymphocytic lymphoma (ORR=100%).  The median time to response was 52 days (range 0-109) in the indolent group and 51 days (range 0-117) in the aggressive group. Median progression-free survival (PFS) was 294 days (range 0-874) in the indolent group and 70 days (range 0-897) in the aggressive group.  At 12 months, the progression-free survival was 45% and 13% in the indolent and aggressive groups, respectively. The median duration of response was 390 days (range 0-825) and 166 days (range 0-786 days) in the indolent and aggressive groups, respectively. The authors reported that the median overall survival was 657 days in the indolent group (range 0-958) and 183 days in the aggressive group (range 0-1017).  At 12 months, the overall survival was 69% in the indolent and 42% in the aggressive lymphoma group. The most common treatment-emergent adverse events (TEAEs) were hyperglycemia (59.5%), hypertension (54.8%), fatigue (48.8%), and diarrhea (40.5%). All were generally manageable. Neutropenia occurred in 28.6% of subjects. Serious drug-related TEAEs were recorded in 32.1% of subjects, including lung infections, diarrhea, febrile neutropenia, pancreatitis, cardiac disorders. There were 10 deaths reported overall, with 4 considered possibly drug-related.  All-grade hematologic toxicities included decreased neutrophil count (34.5%), anemia (28.6%), and decreased platelet count (17.9%).  TEAEs leading to permanent treatment discontinuation were reported in 25.0% of subjects. The authors concluded that, “Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma.”

Further studies are warranted to elucidate the benefit of copanlisib in other conditions.

Background/Overview

Follicular lymphoma is a mostly slow-growing type of non-Hodgkin lymphoma, which is a type of cancer involving the lymphatic system. This system is part of the body’s immune process and is important for fighting infections and invasions. According to the National Cancer Institute, approximately 72,240 people in the United States will be diagnosed with some form of non-Hodgkin lymphoma this year; approximately 20,140 individuals with non-Hodgkin lymphoma will die from the disease in 2017.

The American Cancer Society states that follicular lymphomas are usually slow-growing, but may be quicker growing in some cases.  It usually responds well to treatment, although complete cures are rare.

Copanlisib is a type of drug known as a ‘kinase inhibitor’.  This type of drug works by blocking several enzymes that promote cell growth, which has been found to be an effective approach to treat a variety of cancers.

Definitions

Follicular lymphoma: A type of B-cell non-Hodgkin lymphoma, a cancer of the immune system that is usually indolent (slow-growing). The tumor cells grow as groups to form nodules. There are several subtypes of follicular lymphoma.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

HCPCS

 

 

C9030

Injection, copanlisib, 1 mg [Aliqopa] [Note: code will be deleted 12/31/2018]

 

J9057

Injection, copanlisib, 1 mg [Aliqopa] [Note: code effective 01/01/2019; NOC codes J3590 or J9999 until 12/31/2018]

 

 

 

 

ICD-10 Diagnosis

 

C82.00-C82.99

Follicular lymphoma

C83.00-C83.09

Small cell B-cell lymphoma

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Dreyling M, Morschhauser F, Bouabdallah K, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017; 28(9):2169-2178.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Aliqopa® [Product Information], Whippany, NJ. Bayer HealthCare Pharmaceuticals. September 14, 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf. Accessed on October 31, 2018.
  2. NCCN Clinical Practice Guidelines in Oncology© 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org. Accessed on October 31, 2018.
    • B-Cell Lymphomas (V4.2018). Revised October 31, 2018.
Websites for Additional Information
  1. American Cancer Society. Types of Non-Hodgkin Lymphoma. Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/types-of-non-hodgkin-lymphoma.html. Accessed on August 31, 2018.
Index

Aliqopa
Copanlisib
Follicular lymphoma

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed

11/08/2018

Medical Policy & Technology Assessment Committee (MPTAC) review

Reviewed

10/31/2018

Hematology/Oncology Subcommittee review. Updated References section. Updated Coding section with 01/01/2019 HCPCS changes; added J9057, C9030 deleted 12/31/2018.

 

06/28/2018

Updated Coding section with 07/01/2018 HCPCS changes; added C9030.

New

11/02/2017

MPTAC review

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial document development.