Medical policy: Hematopoietic Cell Transplantation for Primary Amyloidosis

Número de política: MP 9.045

Fecha de entrada en vigor: 5/1/2026

Política

Autologous hematopoietic cell transplantation may be considered medically necessary to treat primary systemic amyloidosis.

Allogeneic hematopoietic cell transplantation is considered investigational to treat primary systemic amyloidosis. No hay pruebas suficientes para apoyar una conclusión general con respecto a los resultados o beneficios para la salud asociados con este procedimiento.

Referencias cruzadas

• MP 9.001 Placental/Umbilical Cord Blood as a Source of Stem Cells

Variaciones del producto

Esta política solo se aplica a ciertos programas y productos administrados por Capital Blue Cross y está sujeta a variaciones en los beneficios. Consulte la información adicional a continuación.

FEP PPO – Refer to FEP Medical Policy Manual .

Descripción/antecedentes

Primary amyloidosis

The primary amyloidoses comprise a group of diseases with an underlying clonal plasma cell dyscrasia. They are characterized by the extracellular deposition of pathologic, insoluble protein fibrils with a beta-pleated sheet configuration that exhibits a pathognomonic red-green birefringence when stained with Congo red dye and examined under polarized light.

These diseases are classified by the type of amyloidogenic protein involved and by the distribution of amyloid deposits. In systemic amyloidosis, the unnatural protein is produced at a site that is remote from the site(s) of deposition, whereas, in localized disease, the amyloid light chain protein is produced at the site of deposition. Primary or amyloid light chain amyloidosis, the most common type of systemic amyloidosis, has an incidence of approximately 9 to 14 cases per million person-years with approximately 4000 new cases in the United States each year.

The typical age at diagnosis is about 50 to 65 years. The amyloidogenic protein in primary amyloidosis is an immunoglobulin light chain or light-chain fragment produced by a clonal population of plasma cells in the bone marrow. While the plasma cell burden in primary amyloidosis is typically low, ranging from 5% to 10%, this disease also may occur in association with multiple myeloma in 10% to 15% of patients.

Deposition of primary amyloidogenic proteins causes organ dysfunction, most frequently in the kidneys, heart, and liver, although the central nervous system and brain may be affected.

Tratamiento

Historically, this disease has had a poor prognosis, with a median survival from diagnosis of approximately 12 months, although outcomes have improved with combination chemotherapy using alkylating agents and autologous hematopoietic stem cell transplantation (HCT).

Emerging approaches include the use of immunomodulatory drugs (e.g., thalidomide, lenalidomide, pomalidomide) and the proteasome inhibitor, bortezomib. The anti-CD38 monoclonal antibody daratumumab/hyaluronidase received approval in July 2021 for treatment of newly diagnosed light-chain amyloidosis in combination with bortezomib, cyclophosphamide, and dexamethasone.

Regardless of the approach, treatment of primary amyloidosis aims at rapidly reducing the production of amyloidogenic monoclonal light chains by suppressing the underlying plasma cell dyscrasia, with supportive care to decrease symptoms and maintain organ function. The therapeutic index of any chemotherapy regimen is a key consideration in the context of underlying organ dysfunction.

Chemotherapy for the treatment of light chain amyloidosis was introduced in 1972 in the form of melphalan and prednisone. This chemotherapy regimen has yielded higher response and longer survival rates than colchicine or prior therapies. Survival after oral melphalan and prednisone (typically 12 to 18 months) is longer than for untreated patients or those given older therapies (10 to 14 months), but more effective regimens have been sought.

Combination therapy with vincristine, doxorubicin, and dexamethasone, a well-established regimen for myeloma, has been investigated. However, because of its toxicity, vincristine/doxorubicin/dexamethasone therapy is usually limited to patients without peripheral neuropathy or cardiomyopathy, both common complications of amyloidosis.

Because conventional regimens rarely cure systemic amyloidosis and because of the close biologic similarity to multiple myeloma, myeloablative chemotherapy with HCT is being investigated for this disease.

Hematopoietic cell transplantation

Hematopoietic cell transplantation refers to the infusion of hematopoietic stem cells to restore bone marrow function in cancer patients who receive bone marrow-toxic doses of drugs with or without whole-body radiotherapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or from a donor (allogeneic HCT).

These cells can be harvested from bone marrow, peripheral blood, or umbilical cord blood. Although cord blood is an allogeneic source, the stem cells in it are antigenically "naïve" and thus are associated with a lower incidence of rejection or graft-versus-host disease (GVHD). Cord blood is discussed in greater detail in MP 9.001.

Autologous HCT

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HCT. The success of autologous HCT is predicated on the ability of cytotoxic chemotherapy with or without radiation to eradicate cancerous cells from the blood and bone marrow.

This permits subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic stem cells obtained from the patient before undergoing bone marrow ablation. As a consequence, autologous HCT is typically performed as consolidation therapy when the patient's disease is in complete response. Patients who undergo autologous HCT are susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not GVHD.

Allogeneic HCT

Immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic HCT. Compatibility is established by typing human leukocyte antigen (HLA) using cellular, serologic, or molecular techniques.

HLA refers to the tissue type expressed at the HLA-A, -B, and -DR loci on each arm of chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci.

The conventional (“classical”) practice of allogeneic HCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to destroy endogenous hematopoietic capability in the recipient.

The beneficial treatment effect in this procedure is due to a combination of initial eradication of malignant cells and subsequent graft-versus-malignancy effect mediated by non-self-immunologic effector cells that develop after engraftment of allogeneic stem cells within the patient’s bone marrow space.

While the slower graft-versus-malignancy effect is considered to be the potentially curative component, it may be overwhelmed by extant disease without the use of pretransplant conditioning. However, intense conditioning regimens are limited to patients who are sufficiently fit medically to tolerate substantial adverse effects that include pre-engraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by cytotoxic drugs.

Furthermore, in any allogeneic HCT, immune suppressive drugs are required to minimize graft rejection and GVHD, which also increase susceptibility to opportunistic infections.

Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses or less intense regimens of cytotoxic drugs or radiation than are used in conventional full-dose myeloablative conditioning treatments.

The goal of RIC is to reduce disease burden and to minimize as much as possible treatment-related morbidity and non-relapse mortality in the period during which the beneficial graft-versus-malignancy effect of allogeneic transplantation develops.

Although the definition of RIC remains variable with numerous versions employed, all seek to balance the competing effects of non-relapse mortality and relapse due to residual disease. These regimens can be viewed as a continuum in effects, from nearly totally myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition.

Patients who undergo RIC with allogeneic HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full donor chimerism, which may be supplemented with donor lymphocyte infusions to eradicate residual malignant cells. For this evidence review, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative, as opposed to fully myeloablative (conventional) regimens.

Situación reglamentaria

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

Fundamento

Summary of evidence

For individuals with primary amyloidosis who receive autologous HCT, the evidence includes a network meta-analysis, randomized controlled trials (RCTs), nonrandomized comparative studies, and large case series. Relevant outcomes are overall survival (OS), disease-specific survival, change in disease status, and treatment-related morbidity and mortality.

For individuals with primary amyloidosis who receive autologous HCT, the evidence includes a network meta-analysis, randomized controlled trials (RCTs), nonrandomized comparative studies, and large case series. Relevant outcomes are overall survival (OS), disease-specific survival, change in disease status, and treatment-related morbidity and mortality. Use of autologous HCT for primary amyloidosis rapidly eradicates the amyloid light chain produced by the clonal plasma cell populations, which is the proximal cause of pathology and subsequent death. This procedure has extended survival rates to a reported 77% at 5 years and 56% at 10 years in patients who respond to treatment. Complete response to treatment has been reported in 34% to 69.6% of patients, while transplant-related mortality rates have declined significantly in more recent studies. Therefore, autologous HCT is an important treatment option for patients who are deemed eligible. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals with primary amyloidosis who receive allogeneic HCT, the evidence includes case reports. Relevant outcomes are OS, disease-specific survival, change in disease status, and treatment-related morbidity and mortality. Evidence on the use of allogeneic HCT is sparse and has shown high treatment-related mortality. Las pruebas son insuficientes para determinar que la tecnología da lugar a una mejora en el resultado neto para la salud.

Definiciones

N/D

Exención de responsabilidad

Las políticas médicas de Capital Blue Cross se utilizan para determinar la cobertura de tecnologías, procedimientos, equipos y servicios médicos específicos. Estas políticas médicas no constituyen un consejo médico y están sujetas a cambios según lo permita la ley o la evidencia clínica aplicable de las pautas de tratamiento independientes. Los proveedores que brindan tratamiento son individualmente responsables de los consejos médicos y el tratamiento de los miembros. Estas políticas no son una garantía de cobertura o pago. El pago de las reclamaciones está sujeto a la determinación del programa de beneficios del miembro y la elegibilidad en la fecha del servicio, y a la determinación de que los servicios son médicamente necesarios y apropiados. El procesamiento final de una reclamación se basa en los términos del contrato que se aplican al programa de beneficios de los miembros, incluidas las limitaciones y exclusiones de beneficios. Si un proveedor o miembro tiene alguna pregunta sobre esta política médica, debe comunicarse con Servicios para proveedores o Servicios para miembros de Capital Blue Cross.

Información de codificación

Nota: Es posible que esta lista de códigos no sea exhaustiva y que los códigos estén sujetos a cambios en cualquier momento. La identificación de un código en esta sección no denota cobertura, ya que la cobertura está determinada por los términos de la información de beneficios del miembro. Además, no todos los servicios cubiertos son elegibles para un reembolso por separado.

Investigational; therefore, not covered

Allogeneic hematopoietic cell transplantation to treat primary systemic amyloidosis.

Cubierto cuando es médicamente necesario

Autologous hematopoietic cell transplantation to treat primary systemic amyloidosis.

Referencias

1. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Systemic Light Chain Amyloidosis. Version 1.2025. Accessed December 2, 2024.
2. National Organization for Rare Disorders (NORD). Amyloidosis. Updated December 2024. Último acceso: 2 de diciembre de 2024.
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6. Dispenzieri A, Lacy MQ, Kyle RA, et al. Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival. J Clin Oncol. Jul 15 2001; 19(14): 3350-6. PMID 11454882
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11. Cai Y, Xu S, Li N, et al. Efficacy of Chemotherapies and Stem Cell Transplantation for Systemic AL Amyloidosis: A Network Meta-Analysis. Front Pharmacol. 2019; 10: 1601. PMID 32063846
12. Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. Sep 13 2007; 357(11): 1083-93. PMID 17855669
13. Parmar S, Kongtim P, Champlin R, et al. Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up. Bone Marrow Transplant. Agosto de 2014; 49(8): 1036-41. PMID 24887378
14. Sharpley FA, Manwani R, Petrie A, et al. Autologous stem cell transplantation vs bortezomib based chemotherapy for the first-line treatment of systemic light chain amyloidosis in the UK. Eur J Haematol. Apr 2021; 106(4): 537-545. PMID 33460466
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19. Madan S, Kumar SK, Lacy MQ, et al. High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement. Blood. Feb 02 2012; 119(5): 1111-22. PMID 22214893
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21. Sharpley FA, Petrie A, Mahmood S, et al. A 24-year experience of autologous stem cell transplantation for light chain amyloidosis patients in the United Kingdom. Br J Haematol. Dec 2019; 187(5): 642-652. PMID 31410841
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29. Centers for Medicare & Medicaid Services. National Coverage Determination (NCD) for Stem Cell Transplantation (Formerly 110.8.1) (110.23). 2024.