Subject: Jakafi SGM 1999-A P2026a

Drug

JAKAFI  (ruxolitinib)

JAKAFI XR  (ruxolitinib)

Policy:

Indications

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications¹

·        Jakafi/Jakafi XR is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.

·        Jakafi/Jakafi XR is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

·        Jakafi/Jakafi XR is indicated for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

·        Jakafi/Jakafi XR is indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Compendial Uses^2,7-8

·        Symptomatic lower risk myelofibrosis

·        Myelofibrosis-associated anemia

·        Accelerated/blast phase myeloproliferative neoplasms

·        Polycythemia vera in patients with inadequate response or loss of response to interferon therapy

·        Polycythemia vera in patients with high-risk disease

·        BCR::ABL1 -like B-cell Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic lymphoma (LL)

·        Chronic myelomonocytic leukemia (CMML)-2

·        T-cell lymphomas - T-cell large granular lymphocytic leukemia and T-cell prolymphocytic leukemia

·        Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) with neutrophilia

·        Essential Thrombocythemia

·        Myeloid/lymphoid neoplasms with eosinophilia and JAK2 rearrangement in blast phase or chronic phase

·        Chimeric antigen receptor (CAR) T-cell-related toxicities

o   Cytokine release syndrome (CRS)

o   Immune effector cell-parkinsonism related to B-cell associated maturation antigen-directed CAR T-cell therapy

·        Immune checkpoint inhibitor-related toxicities

o   Concomitant myositis and myocarditis

o   Hemophagocytic lymphohistiocytosis-like syndrome

All other indications are considered experimental/investigational and not medically necessary.

Documentation

Submission of the following information is necessary to initiate the prior authorization review:

·        For BCR::ABL1-like B-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (LL), medical record documentation confirming either a cytokine receptor-like factor 2 (CRLF2) mutation or a mutation associated with activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway.

·        For myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with neutrophilia: Testing or analysis confirming JAK2 mutation or CSF3R mutation

·        For myeloid and/or lymphoid neoplasms with eosinophilia: Testing or analysis confirming JAK2 rearrangement

Coverage Criteria

Myelofibrosis^1,2

Authorization of 12 months may be granted for the treatment of myelofibrosis.

Polycythemia Vera^1,2

Authorization of 12 months may be granted for the treatment of polycythemia vera when any of the following criteria are met:

·        Member has had an inadequate response, loss of response or intolerance to cytoreductive treatment (e.g., hydroxyurea, peginterferon alfa-2a).

·        Member has high risk disease.

Acute Graft-versus-Host Disease (aGVHD) or Chronic Graft-versus-Host Disease (cGVHD)^1,2,8

Authorization of 12 months may be granted for the treatment of graft-vs-host disease when used in combination with systemic corticosteroids and any of the following criteria are met:

·        Member has steroid-refractory acute GVHD (e.g., progressed within 3 days or did not improve within 7 consecutive days of treatment with prednisone 2 mg/kg/day or equivalent).

·        Member has chronic GVHD and has failed at least one prior line of systemic therapy.

Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LL)^2,6,7

Authorization of 12 months may be granted for the treatment of BCR::ABL1-like B-cell acute lymphoblastic leukemia/lymphoblastic lymphoma for members with either a cytokine receptor-like factor 2 (CRLF2) mutation or a mutation associated with activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway.

Chronic Myelomonocytic Leukemia (CMML)-2²

Authorization of 12 months may be granted for the treatment of symptomatic chronic myelomonocytic leukemia (CMML)-2 in combination with a hypomethylating agent (e.g., azacitidine, decitabine).

T-Cell Large Granular Lymphocytic Leukemia or T-Cell Prolymphocytic Leukemia²

Authorization of 12 months may be granted for the subsequent treatment of T-cell large granular lymphocytic leukemia or symptomatic T-cell prolymphocytic leukemia, as a single agent.

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) with Neutrophilia²

Authorization of 12 months may be granted for the treatment of MDS/MPN with neutrophilia when all of the following are met:

·        Requested medication will be used as a single agent or in combination with a hypomethylating agent (e.g., azacitidine, decitabine).

·        Member is JAK2 mutation or CSF3R mutation positive.

Accelerated/Blast Phase Myeloproliferative Neoplasms²

Authorization of 12 months may be granted for the treatment of symptomatic accelerated/blast phase myeloproliferative neoplasms when used as a single agent or in combination with azacitidine or decitabine.

Essential Thrombocythemia²

Authorization of 12 months may be granted for the treatment of essential thrombocythemia in members who have had an inadequate response or loss of response to hydroxyurea, peginterferon alfa-2a, or anagrelide.

Myeloid/Lymphoid Neoplasms with Eosinophilia²

Authorization of 12 months may be granted for the treatment of myeloid and/or lymphoid neoplasms with eosinophilia and JAK2 rearrangement in the chronic phase or blast phase.

Chimeric Antigen Receptor (CAR) T-Cell-Related Toxicities²

Authorization of 1 month may be granted for treatment of Grade 4 cytokine release syndrome that is refractory to high-dose corticosteroids and anti-IL-6 therapy.

Authorization of 6 month may be granted for treatment of immune effector cell-parkinsonism related to B-cell associated maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy (e.g., idecabtagene vicleucel (Abecma), ciltacabtagene autoleucel (Carvykti)).

Immune Checkpoint Inhibitor-Related Toxicities²

Authorization of 1 month may be granted for treatment of immune checkpoint inhibitor-related concomitant myositis and myocarditis when requested agent is used in combination with abatacept.

Authorization of 1 month may be granted for treatment of hemophagocytic lymphohistiocytosis-like syndrome if member has not responded to five days of corticosteroids.

Continuation of Therapy

Myelofibrosis, Accelerated/Blast Phase Myeloproliferative Neoplasms, Polycythemia Vera, Acute GVHD, Chronic GVHD, and Essential Thrombocythemia

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization who have improvement in symptoms and no unacceptable toxicity.

Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LL), Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) with Neutrophilia, Chronic Myelomonocytic Leukemia (CMML)-2, T-Cell Large Granular Lymphocytic Leukemia, T-Cell Prolymphocytic Leukemia, and Myeloid/Lymphoid Neoplasms with Eosinophilia

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Chimeric Antigen Receptor (CAR) T-Cell-Related Toxicities and Immune Checkpoint Inhibitor-Related Toxicities

All members (including new members) requesting authorization for continuation of therapy must meet all requirements in the coverage criteria section.

Place of Service:

Outpatient

The above policy is based on the following references:

1.     Jakafi/Jakafi XR [package insert]. Wilmington, DE: Incyte Corporation; May 2026.

2.     The NCCN Drugs & Biologics Compendium® © 2026 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed January 14, 2026.

3.     Zeiser R, Burchert A, Lengerke C, et al: Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia 2015; 29(10):2062-2068.

4.     Zeiser R, Burchert A, Lengerke C, et al: Long-term follow-up of patients with corticosteroid-refractory graft-versus-host disease treated with ruxolitinib. Blood 2016; 128(22):4561

5.     Raetz Elizabeth, Loh Mignon. A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib with Chemotherapy in Children with De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia. American Society of Hematology. 2016: 13(3).

6.     Ding YY, Stern JW, Jubelirer TF, et al. Clinical efficacy of Ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGAS-JAK2 fusion and induction failure. Haematologica. 2018 Sep;103(9):e427-e431. doi: 10.3324/haematol.2018.192088. Epub 2018 May 17.

7.     National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Pediatric Acute Lymphoblastic Leukemia. Available at: http://www.nccn.org. Version 1.2026. https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf. Accessed January 20, 2026.

8.     National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation (HCT). Available at: http://www.nccn.org. Version 3.2025. https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf. Accessed January 20, 2026.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

June 14, 2026