Marnetegragene Autotemcel (Kresladi)

Number: 1102

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses marnetegragene autotemcel (Kresladi) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Kresladi has been identified as an Aetna Gene-based, Cellular & Other Innovative Therapies (GCIT®) product. It receives dedicated review by the Aetna GCIT team for Commercial and Medicare lines of business.

Note: Requires Precertification: 

Precertification of marnetegragene autotemcel (Kresladi) is required of all Aetna participating providers and members in applicable plan designs. For precertification of marnetegragene autotemcel (Kresladi), contact National Medical Excellence (NME) at 877-212-8811.  

Note: Unless member's health plan has elected not to require, gene and cellular therapies must be administered at an Aetna Institutes® Gene Based, Cellular and Other Innovative Therapy (GCIT®) Network. For marnetegragene autotemcel (Kresladi), see Aetna Institutes® GCIT Designated Networks. 

  1. Prescriber Specialties

    This medication must be prescribed by or in consultation with an immunologist, hematologist, or physician who specializes in the treatment of leukocyte adhesion deficiency-I (LAD-I).

  2. Criteria for Initial Approval

    Aetna considers a a one-time administration of marnetegragene autotemcel (Kresladi) medically necessary for the treatment of severe leukocyte adhesion deficiency-I (LAD-I) when all of the following criteria are met:

    1. Member is 9 months to less than 10 years of age; and
    2. Member has a diagnosis of severe leukocyte adhesion deficiency-I (LAD-I) confirmed by the presence of biallelic pathogenic variants in the ITGB2 gene and one of the following:

      1. Flow cytometry indicating CD18 expression on less than 2% of neutrophils [polymorphonuclear neutrophils (PMNs)], or
      2. Flow cytometry indicating CD18 expression on greater than 2% of PMNs and both of the following:

        1. CD11a or CD11b expression on less than 2% of PMNs; and
        2. Clinical history or known family history consistent with LAD-I; and

    3. Member meets one of the following:

      1. Member has had at least one prior significant bacterial or fungal infection, or
      2. Member has documented family history of LAD-I; and
    4. Member is an appropriate candidate for hematopoietic stem cell transplant (HSCT) and has no medically-eligible human leukocyte antigen (HLA)-matched sibling donor; and
    5. Member has a negative serology test for human immunodeficiency virus 1 and 2 (HIV-1/HIV-2) and human T-lymphocytic virus 1 and 2 (HTLV-1/HTLV-2); and
    6. Member will be assessed and monitored for the following, as directed in the manufacturer’s prescribing information:

      1. Signs and symptoms of infection
      2. Signs and symptoms of veno-occlusive disease
      3. Neutrophil counts
      4. Platelet counts and bleeding
      5. Hematologic malignancies
      6. Hypersensitivity reactions; and

    7. Member does not have evidence of hepatic dysfunction, defined as:

      1. Bilirubin greater than 1.5 times the upper limit of normal; and
      2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the upper limit of normal; and
    8. Member does not have evidence of renal dysfunction (e.g., eGFR less than 60 ml/min/1.73 m2) or requirement for dialysis or hemodialysis; and
    9. Member does not have evidence of pulmonary dysfunction, defined as:

      1. Need for supplemental oxygen within two weeks of initiating therapy with the requested medication; and
      2. Oxygen saturation less than 90% (by pulse oximetry); and
    10. Member does not have evidence of active metastatic or locoregionally advanced malignancy (including hematologic malignancy); and
    11. Member is not infected with persistent bloodstream pathogens or other serious, untreated infections; and
    12. Member does not have any medical or other contraindication for leukapheresis, bone marrow harvest, or conditioning procedures, in the opinion of the provider; and
    13. Member does not have evidence of significant medical conditions [e.g., poorly controlled diabetes, poorly controlled hypertension, poorly controlled cardiac arrythmia, congestive heart failure; or arterial thromboembolic events (including stroke or myocardial infarction)] within 6 months of initiating treatment with the requested medication; and
    14. Member has not received Kresladi or any other gene therapy previously.

    Aetna considers all other indications as experimental, investigational, or unproven.

  3. Related Policies 

    1. CPB 0351 - Flow Cytometry, Ektacytometry, DNA Ploidy, and S-phase Fraction
    2. CPB 0830 - Hematopoietic Cell Transplantation for Primary Immunodeficiency Disorders

Dosage and Administration

Marnetegragene autotemcel is available as Kresladi, a cell suspension for autologous use and administered as a one-time, single dose intravenous infusion. Kresladi is composed of one or two infusion bags, each containing 0.34 to 6.1 × 106 cells/mL (including 0.32 to 6.1 × 106 CD34+ cells/mL) suspended in a cryopreservation solution. Each infusion bag contains approximately 30 mL of Kresladi.

  • Individuals are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for Kresladi manufacturing.
  • Dosing of Kresladi is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight prior to first apheresis. The minimum recommended dose of Kresladi is 2.8 × 106 CD34+ cells/kg.
  • Ustekinumab administration should be considered prior to mobilization and apheresis and/or prior to Kresladi infusion.
  • Full myeloablative conditioning must be administered between 24 to 48 hours before infusion of Kresladi.
  • Prophylactic antimicrobials should be considered according to institutional guidelines.
  • Kresladi infusion is administered within 30 minutes of the start of thaw.
  • For additional information, refer to the Full Prescribing Information for Kresladi.

Source: Rocket Pharmaceuticals, 2026

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Other CPT codes related to the CPB:
38204 Management of recipient hematopoietic progenitor cell donor search and cell acquisition
38205-38206 Blood-derived hematopoietic progenitor cell harvesting for transplantation per collection
38207-38215 Transplant preparation of hematopoietic progenitor cells
38230 Bone marrow harvesting for transplantation; allogeneic
38232      autologous
38240-38243 Transplantation and post-transplantation cellular infusions
80069 Renal function panel This panel must include the following: Albumin (82040) Calcium, total (82310) Carbon dioxide (bicarbonate) (82374) Chloride (82435) Creatinine (82565) Glucose (82947) Phosphorus inorganic (phosphate) (84100) Potassium (84132) Sodium (84295) Urea nitrogen (BUN) (84520)
80076 Hepatic function panel This panel must include the following: Albumin (82040) Bilirubin, total (82247) Bilirubin, direct (82248) Phosphatase, alkaline (84075) Protein, total (84155) Transferase, alanine amino (ALT) (SGPT) (84460) Transferase, aspartate amino (AST) (SGOT) (84450)
82247-82252, 88720 Bilirubin
82565 Creatinine; blood
84450 Transferase; aspartate amino (AST) (SGOT)
84460      alanine amino (ALT) (SGPT)
85002 Bleeding time
85004 Blood count; automated differential WBC count
85007      blood smear, microscopic examination with manual differential WBC count
85025      complete (CBC), automated (Hgb, Hct, RBC, WBC and platelet count) and automated differential WBC count
85027      complete (CBC), automated (Hgb, Hct, RBC, WBC and platelet count)
85049      platelet, automated
86689 Antibody; HTLV or HIV antibody, confirmatory test (eg, Western Blot)
86701      HIV-1
86702      HIV-2
86703 HIV-1 and HIV-2, single result
87389 Infectious agent antigen detection by immunoassay technique (eg, enzyme immunoassay [EIA], enzyme-linked immunosorbent assay [ELISA], fluorescence immunoassay [FIA], immunochemiluminometric assay [IMCA]), qualitative or semiquantitative; HIV-1 antigen(s), with HIV-1 and HIV-2 antibodies, single result
87390      HIV-1
87391      HIV-2
88182-88189 Flow cytometry
90935-90997 Dialysis
96413 Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug
96415      each additional hour

HCPCS codes covered if selection criteria are met:
Marnetegragene autotemcel (Kresladi)- No specific code

ICD-10 codes covered if selection criteria are met:
D71.1 Leukocyte adhesion deficiency

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
B20 Human immunodeficiency virus [HIV] disease
B97.33 Human T-cell lymphotrophic virus, type I [HTLV-I] as the cause of diseases classified elsewhere
B97.34 Human T-cell lymphotrophic virus, type II [HTLV-II] as the cause of diseases classified elsewhere
B97.35 Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere
C00.0-D49.9 Neoplasms [Metastatic or locoregionally advanced malignancy]
C91.50 Adult T-cell lymphoma/leukemia (HTLV-1-associated) not having achieved remission
C91.51 Adult T-cell lymphoma/leukemia (HTLV-1-associated), in remission
C91.52 Adult T-cell lymphoma/leukemia (HTLV-1-associated), in relapse
Z22.6 Carrier of human T-lymphotropic virus type-1 [HTLV-1] infection
Z99.2 Dependence on renal dialysis

Background

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

  • Kresladi is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in the ITGB2 gene without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant.

    This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Marnetegragene autotemcel, branded as Kresladi (Rocket Pharmaceuticals, Inc.), is an autologous hematopoietic stem cell–based gene therapy manufactured from hematopoietic stem cells obtained through apheresis. Collected cells are enriched for CD34+ cells and transduced ex vivo with LV‑RP‑201, a replication‑incompetent, self‑inactivating lentiviral vector encoding the CD18 β‑subunit of human β2 integrins (ITGB2), under the control of a human chimeric promoter composed of FES and CTSG minimal 5′‑flanking regions. Following transduction in the presence of defined growth factors, the CD34+ cells are washed, formulated into a suspension, and cryopreserved for intravenous administration. After infusion, genetically modified CD34+ hematopoietic stem cells engraft in the bone marrow and differentiate into multiple leukocyte lineages capable of expressing functional CD18 protein, thereby enabling formation of the CD18/CD11a heterodimer (leukocyte function‑associated antigen‑1 [LFA‑1]), which is essential for leukocyte adhesion to the endothelium and migration to sites of infection and inflammation.

Although there are no labeled contraindications, Kresladi is associated with several clinically significant risks related to both the gene therapy product and the required myeloablative conditioning regimen. Serious infections have been reported following administration, with increased susceptibility attributed in part to myeloablative conditioning prior to infusion; close monitoring for signs and symptoms of infection before and after infusion is required, along with administration of prophylactic antimicrobials in accordance with institutional guidelines. Use should be avoided in the presence of active bloodstream infections or other serious, untreated infections, and any blood products required after infusion must be irradiated. Veno‑occlusive disease has occurred following treatment, with heightened risk associated with conditioning; monitoring for clinical signs and liver function abnormalities is recommended during the first month after infusion. Hematologic complications include potential neutrophil engraftment failure, defined as failure to achieve three consecutive absolute neutrophil counts ≥500 cells/microliter by Day 43 post‑infusion, as well as delayed platelet engraftment; ongoing monitoring is required, and rescue treatment using a back‑up CD34+ cell collection should be administered if engraftment failure occurs. Lentiviral vector–mediated insertional oncogenesis represents a lifelong risk, with possible development of hematologic malignancy; long‑term surveillance including at least annual complete blood counts with differential and integration site analysis, as clinically indicated, is recommended for at least 15 years following treatment. Hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) in the formulation, regardless of prior exposure. Anti‑retroviral medications may interfere with product manufacturing and should be discontinued for an appropriate washout period prior to mobilization and apheresis, with HIV infection adequately ruled out before proceeding; additionally, PCR‑based HIV testing may yield false‑positive results following treatment and should be avoided. Individuals treated with Kresladi should not donate blood, organs, tissues, or cells for transplantation at any time in the future.

Kresladi has not been studied in patients with HIV-1, HIV-2, HTLV-1, or HTLV-2. Thus, a negative serology test for HIV is necessary to ensure acceptance of apheresis material for Kresladi manufacturing. The prescribing information states that apheresis material from patients with a positive test for HIV will not be accepted for Kresladi manufacturing.

The most common non-laboratory adverse reactions (30% or more) include mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection. The most common laboratory adverse reactions (occurring 30% or more) include hemoglobin decreased, platelet count decreased, neutrophil count decreased, leukocyte count decreased, aspartate aminotransferase increased, and alanine aminotransferase increased.

Drug interactions may occur with anti-retrovirals. The prescribing information for Kresladi states that patients should not take anti-retroviral medications for one month prior to mobilization, or for the expected duration required for elimination of the anti-retroviral medications, and until all cycles of apheresis are completed.

The safety and effectiveness of immunization with live viral vaccines during or after treatment with Kresladi have not been established. As a precaution, vaccination with live vaccines is not recommended within the 6 weeks preceding initiation of myeloablative conditioning or until hematologic recovery has occurred following Kresladi treatment. When feasible, recommended childhood immunizations should be completed prior to the start of myeloablative conditioning to reduce infectious risk during the treatment period. Additionally, the safety and effectiveness have not been established in pregnant and/or lactating women. There is no available data regarding the presence of Kresladi in human milk, the effect on the breastfed infant, and the effects on milk production. Because of the potential risks associated with myeloablative conditioning, breastfeeding should be discontinued during conditioning.

Leukocyte Adhesion Deficiency

Leukocyte adhesion deficiency (LAD) is a rare, autosomal recessive primary immunodeficiency characterized by defective leukocyte adhesion and migration due to abnormalities in cellular adhesion molecules. The disorder results in impaired extravasation of leukocytes from the circulation to sites of infection, leading to an attenuated inflammatory response, including failure of pus formation, poor wound healing, and recurrent bacterial infections. LAD is classified into three subtypes based on the underlying molecular defect: LAD type I (LAD‑I), caused by mutations in the ITGB2 gene encoding the β2‑integrin subunit CD18; LAD type II, due to impaired fucosylation with absence of sialyl Lewis X selectin ligands; and LAD type III, caused by mutations in FERMT3 (kindlin‑3) that disrupt integrin activation. LAD‑I is the most common form and is estimated to affect approximately 1 in 1 million individuals annually. It frequently presents in infancy or early childhood with recurrent, indolent bacterial infections, delayed umbilical cord separation, marked leukocytosis, and absence of purulence at infection sites. Severe LAD‑I is associated with high early mortality in the absence of definitive treatment, while milder phenotypes may survive into adulthood with ongoing infectious morbidity.

Diagnostic evaluation of LAD‑I relies on immunologic and molecular testing to confirm defective leukocyte adhesion and migration. Flow cytometry is the definitive diagnostic test, demonstrating absent or markedly reduced expression of CD18 and its associated CD11 subunits on the surface of leukocytes using monoclonal antibodies. Sequence analysis using genetic testing is performed to define the exact molecular defect in the beta‑2 subunit encoded by the ITGB2 gene. Additional laboratory evaluation commonly reveals persistent leukocytosis with neutrophilia, largely preserved quantitative serum immunoglobulin levels, and variable functional antibody activity, while specialized assays demonstrate impaired leukocyte chemotaxis, neutrophil mobility, and phagocytic function. Diagnostic assessment is frequently supplemented by infectious disease studies, lymphocyte subset analysis, complement evaluation, and routine hematologic and radiologic testing to assess disease severity and complications and to exclude other causes of immunodeficiency. Management of LAD-I is guided by disease severity, with allogeneic hematopoietic stem cell transplantation (HSCT) serving as curative therapy for severe cases and recommended early due to the high risk of fatal infections in the absence of definitive treatment. Supportive management includes close infection surveillance, early and aggressive antimicrobial therapy, prophylaxis during high-risk procedures, and meticulous skin and dental care. 

Booth et al. (2025) investigated the role of the β2 common integrin subunit CD18, which is essential for leukocyte-endothelial adhesion and extravasation to inflamed or infected tissues. Mutations in ITGB2, the gene encoding CD18, lead to LAD-I, an inborn error of immunity that results in frequent life-threatening infections and a high mortality risk in affected children. While allogeneic HSCT is a curative option, it faces challenges such as donor availability, a high incidence of graft-versus-host disease, and graft failure. In a phase 1-2, multinational, open-label study (NCT03812263, NCT06282432), 9 children with severe LAD-I were treated with marnetegragene-autotemcel (marne-cel), a gene therapy involving autologous CD34+ hematopoietic stem cells transduced with a self-inactivating lentiviral vector containing human ITGB2, and were followed for 24 months. The primary efficacy end point of the phase 2 study was survival without allogeneic HSCT (HSCT-free survival) at least 1 year after marne-cel infusion and at 2 years of age among the patients who were younger than 1 year of age at enrollment, tested against a null hypothesis of survival of 39% of the patients. Interim data from 6 patients in the long-term follow-up study were also reported. Serious adverse events related to myeloablative busulfan conditioning were noted, but no adverse events attributed to gene therapy were reported, and there were no cases of graft failure. The investigators found that HSCT-free survival was 100% (95% confidence interval [CI], 66 to 100) at 1 year post-infusion (P<0.001), with all patients enrolled under 1 year of age surviving beyond 2 years. Additionally, pretreatment neutrophilia and skin abnormalities associated with LAD-I resolved, and the annualized incidence of infection-related hospitalizations beyond 90 days after engraftment was significantly lower – 74.45% for general hospitalizations, 81.95% for prolonged hospitalizations, and 84.90% for serious infections – compared to the period before marne-cel infusion. These investigators concluded that lentiviral vector-transduced autologous CD34+ HSCT effectively treated severe LAD-I.

In March 2026, the U.S. FDA granted accelerated approval of Kresladi for the treatment of pediatric patients with severe LAD-I due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic HSCT. Approval was based on the safety and efficacy outcomes in one open-label, single-arm, multicenter study (NCT03812263) that found increases in neutrophil CD18 and CD11a cell surface expression (disease-specific biomarkers indicative of improved immune activity), at month 12 with sustained effect through month 24 post-infusion. Increases in neutrophil CD18 and CD11a cell surface expression reflect improved function of a protein complex of the two biomarkers on the surface of neutrophils which is used as a surrogate endpoint that "is reasonably likely to predict clinical benefit in LAD-I for accelerated approval". The clinical benefit of Kresladi will be confirmed in patients with severe LAD-I through post-marketing requirements. The most common side effects identified in the clinical study included anemia, low platelet and white blood cell counts, mouth sores, upper respiratory infections, viral infections, fever, febrile neutropenia, nausea, vomiting, skin infection, rash, vascular device-related infection, and increased liver enzymes (FDA, 2026).

References

The above policy is based on the following references:

  1. Booth C, Sevilla J, Almarza E, et al. Lentiviral gene therapy for severe leukocyte adhesion deficiency type 1. N Engl J Med. 2025;392(17):1698-1709.
  2. Justiz Vaillant AA, Ahmad F. Leukocyte adhesion deficiency. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; updated July 3, 2023.
  3. Rocket Pharmaceuticals, Inc. Kresladi (marnetegragene autotemcel) suspension for intravenous infusion. Prescribing Information. Cranbury, NJ: Rocket Pharmaceuticals; March 2026.
  4. U.S. Food and Drug Administration (FDA). FDA approves first gene therapy for severe leukocyte adhesion deficiency type I. FDA News Release. Silver Spring, MD; March 26, 2026.