Sunflower Health Plan REBLOZYL, Luspatercept-aamt Form

Luspatercept-aamt (Reblozyl®) is an erythroid maturation agent. FDA Approved Indication(s) Reblozyl is indicated for the treatment of anemia in adult patients with: • Beta thalassemia who require regular red blood cell (RBC) transfusions • Very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions without previous erythropoiesis stimulating agent use (ESA-naïve) • Very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) failing an erythropoiesis stimulating agent and requiring 2 or more RBC units over 8 weeks Limitation(s) of use: Not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Reblozyl is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Transfusion Dependent Beta Thalassemia (must meet all): 1. Diagnosis of transfusion-dependent thalassemia (TDT) with one of the following genotypes (a or b): a. Beta thalassemia; b. Hemoglobin E/beta thalassemia; 2. Prescribed by or in consultation with a hematologist; 3. Age ≥ 18 years; 4. Total volume of transfusions exceeds 6 RBC units (see Appendix D) within the last 6 months; 5. No transfusion-free period ≥ 35 days within the last 6 months; 6. Documentation of baseline transfusion burden within the last 6 months; 7. Dose does not exceed 1 mg/kg every 3 weeks. Page 1 of 10 CLINICAL POLICY Luspatercept-aamt Approval duration: 2 months (2 doses) B. Myelodysplastic Syndromes (must meet all): 1. Diagnosis of MDS-RS or MDS/MPN-RS-T that meets one of the following classifications (a, b, or c) (see Appendix E): a. Very low, low, or intermediate risk as classified by IPSS-R; b. Low/intermediate-1 risk as classified by IPSS; c. Very low, low, or intermediate risk as classified by WPSS; 2. Prescribed by or in consultation with a hematologist or oncologist; 3. Age ≥ 18 years; 4. Member is dependent on RBC transfusions; 5. If member has MDS with ring sideroblasts < 15% (or ring sideroblasts < 5% with SFB3B1 mutation), failure of an erythropoiesis-stimulating agent (ESA) (see Appendix B and D), unless one of the following applies (a or b): a. Clinically significant adverse effects are experienced or all are contraindicated; b. Documentation of current serum erythropoietin > 500 mU/mL; 6. Member does not have del(5q) cytogenetic abnormality; 7. Request meets one of the following (a or b):* a. Dose does not exceed 1 mg/kg every 3 weeks; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 2 months (2 doses) C. Other diagnoses/indications (must meet 1 or 2): 1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or 2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. II. Continued Therapy A. Transfusion Dependent Beta Thalassemia (must meet all): 1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 2 of 10 CLINICAL POLICY Luspatercept-aamt b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); 2. Member meets one of the following (a or b): a. For members who have received > 9 weeks of treatment (> 3 doses): Member is responding positively to therapy as evidenced by at least a 33% reduction in transfusion burden from baseline; b. Request is for a dose increase and member has not yet received 9 weeks of treatment (3 doses) at the maximum dose of 1.25 mg/kg; 3. If request is for a dose increase, new dose does not exceed (a or b): a. 1 mg/kg every 3 weeks; b. 1.25 mg/kg every 3 weeks, and documentation supports inadequate response to 1 mg/kg dosing. Approval duration: 6 months B. Myelodysplastic Syndromes (must meet all): 1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Reblozyl for a covered indication and has received this medication for at least 30 days; 2. Member meets one of the following (a or b): a. Member is responding positively to therapy as evidenced by a decreased transfusion burden; b. Request is for a dose increase; 3. If request is for a dose increase, request meets one of the following (a, b, c, or d):* a. New dose does not exceed 1 mg/kg every 3 weeks; b. New dose does not exceed 1.33 mg/kg every 3 weeks, and documentation supports lack of transfusion independence after 2 consecutive doses at 1 mg/kg dosing; c. New dose does not exceed 1.75 mg/kg every 3 weeks, and documentation supports lack of transfusion independence after 2 consecutive doses at 1.33 mg/kg dosing; d. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 6 months (2 months [2 doses] if request is for a dose increase) B. Other diagnoses/indications (must meet 1 or 2): 1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: Page 3 of 10 CLINICAL POLICY Luspatercept-aamt CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or 2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ESA: erythropoiesis-stimulating agent FDA: Food and Drug Administration G-CSF: granulocyte colony stimulating factor Hb: hemoglobin IPSS: International Prognostic Scoring System IPSS-R: International Prognostic Scoring System - Revised MDS: myelodysplastic syndromes MDS-RS: myelodysplastic syndromes with ring sideroblasts MDS/MPN-RS-T: myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis TDT: transfusion dependent thalassemia WPSS: WHO Classification-based Scoring System Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization. Drug Name Dosing Regimen Procrit®, Epogen®, Retacrit® (epoetin alfa)* MDS: 40,000 to 60,000 SC units 1 to 2 times per week every week MDS: 150 to 300 mcg SC every other week Aranesp® (darbepoetin alfa)* Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. *Off-label Target hemoglobin up to 12 g/dL Dose Limit/ Maximum Dose Target hemoglobin up to 12 g/dL Appendix C: Contraindications/Boxed Warnings None reported Page 4 of 10 CLINICAL POLICY Luspatercept-aamt Appendix D: General Information • Conversion of RBC units from mL: 1 RBC unit in this criteria refers to a quantity of packed RBCs approximately 200-350 mL. o Sites who use transfusion bags within this range, or ≥ 350 mL, the conversion in units should be done by dividing the volume transfused to the patient by 350 mL, o Sites who use transfusion bags < 200 mL, the conversion in units should be done by dividing the volume transfused to the patient by 200 mL. • MDS and serum erythropoietin level o According to NCCN, for the treatment of symptomatic anemia in MDS with ring sideroblasts ≥ 15% (or ring sideroblasts ≥ 5% with an SF3B1 mutation), a trial of either recombinant human erythropoetin or darbepoetin in combination with or without a granulocyte colony stimulating factor (G-CSF) is recommended when serum erythropoietin level is ≤ 500 mU/mL. If serum erythropoietin level is > 500 mU/mL for this indication, Reblozyl is recommended. • MDS/MPN-RS-T indication o During regulatory review of the MEDALIST data by the FDA, a post-hoc re- classification of patients using the WHO 2016 criteria was conducted to assess the efficacy and safety of Reblozyl in patients with MDS/MPN-RS-T. Among the 229 patients enrolled in MEDALIST, 23 patients were found to have a diagnosis of MDS/MPN-RS-T following this re-classification. In these patients with MDS/MPN- RS-T, a greater proportion of patients treated with Reblozyl (64.3%; n = 9/14) achieved the primary endpoint of transfusion independence for at least 8 weeks during weeks 1-24 compared to placebo (22.2%; n = 2/9). • MDS COMMANDS trial subgroup analysis o The primary outcome of red blood cell transfusion independence for 12 weeks with a mean hemoglobin increase ≥ 1.5 g/dL was seen in 59% of the luspatercept group and 31% of the epoetin alfa group. The primary outcome was seen more often in MDS patients with positive ring sideroblasts treated with luspatercept compared to ESA (70% met in the luspatercept group compared to 31% met in the ESA group in SFB1 positive patients, and 42% met in the luspatercept group compared to 32% met in the ESA group with SFB1 negative patients). There was no difference seen (i.e., similar treatment benefit) between luspatercept and ESA use in patients with negative ring sideroblasts. • NCCN guidelines for MDS o Current NCCN guidelines for Myelodysplastic Syndromes (version 2.2023) recommend luspatercept as first-line therapy for MDS with ring sideroblasts ≥ 15% (or ring sideroblasts ≥ 5% with an SF3B1 mutation). ESA is recommended as the preferred treatment for MDS with ring sideroblasts < 15% (or ring sideroblasts < 5% with SF3B1 mutation). Appendix E: MDS Risk Classification • International Prognostic Scoring System - Revised (IPSS-R) classification: Risk Category Very low Low Intermediate Risk Score ≤ 1.5 < 1.5 – 3 < 3 – 4.5 Page 5 of 10 CLINICAL POLICY Luspatercept-aamt • Risk Score Risk Category < 4.5 – 6 High Very high > 6 International Prognostic Scoring System (IPSS) classification: Risk Category Low Intermediate-1 Intermediate-2 High Risk Score 0 0.5 – 1 1.5 – 2 2.5 – 3.5 • WHO Classification-based Prognostic Scoring System (WPSS) classification: Risk Category Very low Low Intermediate High Very high Risk Score 0 1 2 3 – 4 5 – 6 V. Dosage and Administration Indication Dosing Regimen TDT 1 mg/kg SC once every 3 weeks Maximum Dose 1.25 mg/kg If a patient does not achieve a reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase to max dose of 1.25 mg/kg. If a patient does not achieve a reduction in RBC transfusion burden after 3 consecutive doses (9 weeks) at 1.25 mg/kg, discontinue treatment. Initial: 1 mg/kg SC once every 3 weeks 1.75 mg/kg MDS Dose increases for insufficient response after initiation of treatment: If a patient is not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase the dose to 1.33 mg/kg SC every 3 weeks. If a patient is not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1.33 mg /kg dose level, increase the dose to a maximum of 1.75 mg/kg SC every 3 weeks. Discontinue if a patient does not experience a decrease in transfusion burden after 9 weeks of treatment (administration of 3 doses) at 1.75 mg/kg Page 6 of 10 CLINICAL POLICY Luspatercept-aamt VI. Product Availability Single dose vials for injection: 25 mg, 75 mg VII.