Isatuximab-irfc (Sarclisa)

Number: 0969

Policy

Note: REQUIRES PRECERTIFICATION

Precertification of Sarclisa (isatuximab-irfc) is required of all Aetna participating providers and members in applicable plan designs. For precertification, call (866) 752-7021 (Commercial), (866) 503-0857 (Medicare), or fax (866) 267-3277.

Aetna considers isatuximab-irfc (Sarclisa) medically necessary for the treatment of multiple myeloma when all of the following criteria are met:

1. The member has previously received at least two prior therapies for multiple myeloma, including lenalidomide and a proteasome inhibitor; and

2. The requested medication will be used in combination with pomalidomide and dexamethasone

Aetna considers continued treatment with isatuximab-irfc (Sarclisa) medically necessary in members requesting reauthorization for a medically necessary indication when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Aetna considers Sarclisa (isatuximab-irfc) therapy experimental and investigational for members receiving concomitant therapy with a proteasome inhibitor [e.g., bortezomib (Velcade), ixazomib (Ninlaro), carfilzomib (Kyprolis)] because the safety and effectiveness of this combination has not been established.

Dosing Recommendations

Premedicate with dexamethasone, acetaminophen, H2 antagonists, and diphenhydramine. The recommended dose of Sarclisa is 10 mg/kg as an intravenous infusion every week for 4 weeks followed by every 2 weeks in combination with pomalidomide and dexamethasone until disease progression or unacceptable toxicity.

See Full Prescribing Information for instructions on preparation and administration.

Source: sanofi-aventis 2020.

Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Treatment of multiple myeloma, in combination with pomalidomide and dexamethasone, for adult patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

On March 02, 2020, the U.S. Food and Drug Administration approved Sarclisa (isatuximab-irfc), in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Isatuximab, administered through intravenous (IV) infusion, is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumor activity via multiple mechanisms of action. In a phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. 

The FDA approved isatuximab based on the results of a randomized, multicenter, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions (Attal 2019; ICARIA-MM; NCT02990338). The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. Patients were randomly assigned (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomization was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (<75 years vs ≥75 years). Treatments were assigned based on a permuted blocked randomization scheme with a block size of four. The isatuximab-pomalidomide-dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. Between Jan 10, 2017, and Feb 2, 2018, three hundred and seven patients were randomly assigned to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; p=0·001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 (9%) in the pomalidomide-dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection). The authors concluded the addition of isatuximab to pomalidomide-dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor.

Isatuximab can cause serious side effects, which include the following. Isatuximab can cause IV infusion-related reactions. In a grade three or higher (severe) reaction, the isatuximab infusion should be permanently discontinued and health care professionals should institute appropriate medical management. Isatuximab can also cause neutropenia and health care professionals should monitor a patient’s complete blood cell count periodically during treatment, as well as monitor patients with neutropenia for signs of infection. Higher incidences of second primary malignancies (a second primary cancer that may occur in the same tissue or organ as the first cancer or in another region of the body) were observed in a controlled clinical trial of patients with multiple myeloma receiving Sarclisa. Therefore, health care professionals should monitor patients for the development of a second primary malignancy when taking Sarclisa.

Laboratory test interference may be experienced with isatuximab . Blood banks should be informed that patients are receiving isatuximab because the drug may interfere with certain tests that are done by blood banks (such as antibody screening) for patients who need a blood transfusion. Health care professionals should type and screen patients prior to starting treatment with isatuximab. Isatuximab may interfere with the assays (tests) used to monitor M-protein, which may impact the determination of complete response. Health care professionals should advise pregnant women that isatuximab may cause harm to a developing fetus. Women who are pregnant should not use isatuximab. Women planning to become pregnant should use effective contraceptives during and for at least five months after treatment.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96413, 96415	Intravenous chemotherapy administration
HCPCS codes covered if selection criteria are met:
J9227	Injection, isatuximab-irfc, 10 mg
Other HCPCS codes related to the CPB:
Pomalidomide, lenalidomide - no specific code
J1094	Injection, dexamethasone acetate, 1 mg
ICD-10 codes covered if selection criteria are met:
C90.00 - C90.02	Multiple myeloma

The above policy is based on the following references: