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.
According to the American Cancer Society, in 2020, there will be approximately 32,110 new cases of multiple myeloma (MM) in the United States: 18,130 men and 13,980 women. Additionally, about 12,960 deaths due to MM are expected to occur. Almost all patients with MM who survive initial treatment will eventually relapse, experiencing relapsing-remitting MM (RRMM). Treatment options for patients with RRMM include hematopoietic cell transplantation (HCT), a re-challenge of the previous chemotherapy regimen, or a trial of a new regimen. Factors used to determine the choice of therapy include risk stratification (i.e. high- or standard-risk disease), prior treatments used, and the duration of response to these treatments. Medications used include Velcade (bortezomib), Kyprolis (carfilzomib), Revlimid (lenalidomide), Pomalyst (pomalidomide), Darzalex (daratumumab), Ninlaro (ixazomib), Empliciti (elotuzumab), Farydak (panobinostat), and Doxil (doxorubicin liposome). Xpovio (selinexor) is also available for patients who have had at least four prior therapies. In the triple-drug regimens that are increasingly the norm for treating MM, patients typically receive one or two active agents in combination with the steroid dexamethasone and are treated until disease progression, after which another dexamethasone-containing regimen is given.
On March 2, 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. Sarclisa (isatuximab-irfc), administered through intravenous (IV) infusion, is a CD38-directed cytolytic antibody that works by helping certain cells in the immune system attack multiple myeloma cancer cells.
The approval of Sarclisa (isatuximab-irfc) is based on results of the Phase 3 ICARIA-MM (NCT 02990338) trial, which examined the use of Sarclisa with Pomalyst (pomalidomide) and dexamethasone compared to Pomalyst with dexamethasone (Pd). ICARIA-MM is an open-label, multicenter Phase 3 clinical study that included 307 patients with relapsed/refractory multiple myeloma who received ≥2 prior lines of treatment, including Revlimid and a proteasome inhibitor such as Velcade, Kyprolis, or Ninlaro. The median patient age was 67 years. In addition, patients had received a median of 3 (range, 2-11) prior lines of therapy. At a median follow-up of 11.6 months, the median PFS was 11.53 months with the Sarclisa (isatuximab-irfc) regimen compared with 6.47 months with Pd alone. OS data were not yet mature at the time of analysis. The median OS was not reached in either arm. The 1-year OS rate was 72% with the Sarclisa (isatuximab-irfc) arm compared with 63% with Pd-alone arm. The ORR in the Sarclisa (isatuximab-irfc) arm showed a stringent complete response (sCR) rate of 4.5%, a very good partial response rate (VGPR) of 27.3%, and a partial response (PR) rate of 28.6%. This compares to the non-Sarclisa (isatuximab-irfc) arm, which showed response rates of 2.0%, 6.5%, and 26.8%, respectively. In addition, the median time to first response was 35 days with the Sarclisa (isatuximab-irfc) arm compared to 58 days with Pomalyst-alone arm. The median duration of treatment was 41 weeks (range, 1.3–76.7) in the Sarclisa (isatuximab-irfc) arm compared to 24.0 weeks (range, 1.0–73.7) in the Pomalyst-alone arm. In the Sarclisa (isatuximab-irfc) arm, 56.5% of patients discontinued treatment compared to 74.5% of patients in the Pomalyst-alone arm.
As per the FDA labeled package insert, common side effects for patients taking Sarclisa (isatuximab-irfc) were neutropenia (abnormally low levels of white blood cells), infusion-related reactions, pneumonia (infection of the air sacs in one or both of the lungs), upper respiratory tract infection, diarrhea, anemia, lymphopenia (decrease in the level of white blood cells) and thrombocytopenia (abnormally low levels of platelets). Sarclisa (isatuximab-irfc) can cause serious side effects, which include IV infusion-related reactions, neutropenia, and higher incidences of second primary malignancies were observed in a controlled clinical trial of patients with multiple myeloma receiving Sarclisa (isatuximab-irfc). As per the package insert, health care professionals should advise pregnant women that Sarclisa (isatuximab-irfc) may cause harm to a developing fetus.
As per the FDA labeled package insert, the recommended dose of Sarclisa (isatuximab-irfc) 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.
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis.
2. Sarclisa (isatuximab-irfc) is medically necessary for the FDA-approved treatment of multiple myeloma in adult members who meet ALL of the following criteria:
3. When Sarclisa (isatuximab-irfc) is considered medically necessary, initial therapy will be approved for 6 months at the following FDA-approved dose:
- Member is 18 years of age or older
- Member has an ECOG performance score of 0-1
- Member has relapsed or refractory multiple myeloma (documentation of diagnosis provided)
- Member has tried and failed at least two prior lines of treatment including ≥ 2 consecutive cycles of lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) given alone or in combination
- Member will be receiving requested drug in combination with pomalidomide and dexamethasone
- ·Member most not have ANY of the following:
- Prior pomalidomide therapy
- Prior allogenic hematpoietic stem cell transplant with active graft versus host disease
- Prior allogenic HSC transplant with active graft versus host disease and/or were under immunosuppressive treatment within the last 2 months
- Known to have HIV (human immunodeficiency virus), or active hepatitis A, B or C infection
- Absolute neutrophil count (ANC) < 1000 per mcL (1 x 109/L)
[INFORMATIONAL NOTE: In the clinical trial, pamolidomide 4 mg was taken orally once daily from day 1 to day 21 of each 28-day cycle. Low dose dexamethasone 40 mg (20mg for patients ≥75 years of age) administered orally or by IV infusion, was given on days 1, 8, 15, and 22 of each 28-day cycle.
- 10 mg/kg actual body weight administered as an intravenous (IV) infusion in combination with pomalidomide and dexamethasone, according to the table below:
Days 1, 8, 15 and 22 (once every weekly)
Cycle 2 and beyond
Days 1, 15 (once every 2 weeks)
- Each treatment cycle consists of a 28-day period. Treatment is repeated until disease progression or unacceptable toxicity.
As per the FDA labeled package insert,
Recommended Pre-medications: Administer the following premedications prior to Sarclisa infusion to reduce the risk and severity of infusion-related reactions:
· Dexamethasone 40 mg orally or intravenously (or 20 mg orally or intravenously for patients ≥75 years of age).
The above recommended dose of dexamethasone (orally or intravenously) corresponds to the total dose to be administered only once before infusion as part of the premedication and of the backbone treatment, before Sarclisa and pomalidomide administration. Administer the recommended premedication agents 15 to 60 minutes prior to starting a Sarclisa infusion.
· Acetaminophen 650 mg to 1000 mg orally (or equivalent).
· H2 antagonists.
· Diphenhydramine 25 mg to 50 mg orally or intravenously (or equivalent). The intravenous route is preferred for at least the first 4 infusions.
Dose modifications: No dose reduction of Sarclisa is recommended. Dose delay may be required to allow recovery of blood counts in the event of hematological toxicity.
Missed dose: If a dose is missed, the dose should be administered as soon as possible and the treatment schedule should be adjusted accordingly, maintaining the treatment interval.]
4. Continuation of Sarclisa (isatuximab-irfc) will be approved every 12 months at the FDA-approved dose when the member meets all of the following criteria:
- There are no unacceptable toxicities (e.g. infusion-related reactions, neutropenia, secondary primary malignancies)
- The member has response to therapy (e.g. lack of disease progression)
5. Sarlisa (istauximab-irfc) is considered investigational for all other indications.
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.
1. Sarclisa (isatuximab-irf). [Package insert] Sanofi-Aventis. Bridgewater, NJ. March 2020.
2. Attal M, Richardson P, Rajkumar S, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019; 394 (10214); 2096-2107.
3. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. Multiple Myeloma. Version 3.2020. Accessed March 24, 2020.
4. National Comprehensive Cancer Network (NCCN) Compendia. Sarclisa. Accessed March, 31, 2020.
5. FDA Approves New Therapy for Patients with Previously Treated Multiple Myeloma. FDA News Release. March 2, 2020. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-patients-previously-treated-multiple-myeloma. Accessed March 24, 2020.
6. ClincalTrials.gov. Multinational clinical study comparing isatuximab, pomalidomide, and dexamethasone in refractory or relapsed multiple myeloma patients (ICARIA-MM). NCT02990338. Available at: https://clinicaltrials.gov/ct2/show/NCT02990338
7. Formulary Submission Dossier: Sarclisaź (isatuximab-irfc) for Relapsed Refractory Multiple Myeloma. Sanofi Genzyme. March 2020.
8. Sarclisa (istauximab-irfc). New Drug Review. IPD Analytics. March 2020
(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.)
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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