Medical policy: Hematopoietic Cell Transplantation for Waldenstrom Macroglobulinemia

Número de política: MP 9.046

Fecha de entrada en vigor: 10/1/2026

Política

Autologous hematopoietic cell transplantation may be considered medically necessary as salvage therapy of chemosensitive Waldenstrom macroglobulinemia.

Allogeneic hematopoietic cell transplantation is considered investigational to treat Waldenstrom macroglobulinemia. No hay pruebas suficientes que respalden una conclusión con respecto a los resultados o beneficios en la salud asociados con este procedimiento.

Referencias cruzadas

• MP 9.042 Hematopoietic Cell Transplantation for Non-Hodgkin Lymphomas
• 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 the FEP Medical Policy Manual. The FEP Medical Policy Manual can be found at: FEP Medical Policy Manual.

Descripción/Antecedentes

Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM) is a clonal disorder of B lymphocytes that accounts for 1% to 2% of hematologic malignancies, with an estimated 1500 new cases annually in the United States. Symptoms include weakness, headaches, stroke-like symptoms (confusion, loss of coordination), vision problems, excessive bleeding, unexplained weight loss, and frequent infections. The median age of WM patients is 63 to 68 years, with men comprising 55% to 70% of cases. Median survival of WM ranges from 5 to 10 years, with age, hemoglobin concentration, serum albumin level, and b₂-microglobulin level as predictors of outcome.

The Revised European American Lymphoma and World Health Organization classification and a consensus group formed at the Second International Workshop on Waldenström's Macroglobulinemia recognize WM primarily as a lymphoplasmacytic lymphoma with an associated immunoglobulin M (IgM) monoclonal gammopathy. The definition also requires the presence of a characteristic pattern of bone marrow infiltration with small lymphocytes demonstrating plasmacytic differentiation with variable cell surface antigen expression. The Second International Workshop indicated no minimum serum concentration of IgM is necessary for a diagnosis of WM.

Tratamiento

The goal of therapy for patients with WM is to achieve symptomatic relief and reduce organ damage without compromising quality of life. Treatment of WM is indicated only in symptomatic patients and should not be initiated solely on the basis of serum IgM concentration. Clinical and laboratory findings that indicate the need for therapy of diagnosed WM include a hemoglobin concentration less than 10 g/dL; platelet count less than 100,000/mL; significant adenopathy or organomegaly; symptomatic Ig-related hyperviscosity (>50 g/L); severe neuropathy; amyloidosis; cryoglobulinemia; cold-agglutinin disease; or evidence of disease transformation.

Primary chemotherapeutic options in patients that may undergo autologous hematopoietic cell transplantation (HCT) often combine rituximab with other agents (e.g., dexamethasone, cyclophosphamide, bortezomib, bendamustine), but other agents may also be used including purine analogues (cladribine, fludarabine). Plasma exchange is indicated for acute treatment of symptomatic hyperviscosity.

Conventional preparative conditioning for hematopoietic cell transplantation

The conventional ("classical") practice of allogeneic hematopoietic cell transplantation (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 that develops after engraftment of allogeneic stem cells within individuals' bone marrow space. While the slower graft-versus-malignancy effect is considered the potentially curative component, it may be overwhelmed by extant disease without the use of pretransplant conditioning. However, intense conditioning regimens are limited to individuals who are sufficiently fit medically to tolerate substantial adverse events that include pre-engraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allogeneic HCT, immune suppressant drugs are required to minimize graft rejection and graft-versus-host disease, which also increases susceptibility of the patient to opportunistic infections.

The success of autologous HCT is predicated on the ability of cytotoxic chemotherapy with or without radiotherapy 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 individual before undergoing bone marrow ablation. As a consequence, autologous HCT is typically performed as consolidation therapy when the individual's disease is in complete remission. Individuals who undergo autologous HCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment but not graft-versus-host disease.

Reduced-intensity conditioning for allogeneic HCT

Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses or less intense regimens of cytotoxic drugs or radiotherapy than are used in conventional full-dose myeloablative conditioning treatments. The goal of RIC is to reduce disease burden but also to minimize as much as possible associated 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 arbitrary, with numerous versions employed, all seek to balance the competing effects of non-relapse mortality and relapse due to residual disease. RIC 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 individual condition. Individuals 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 (FDA) regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation, title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

Fundamento

Summary of evidence

For individuals who have WM who receive HCT, the evidence includes case series. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related mortality and morbidity. Several retrospective series have evaluated HCT for WM. Analyses of registry data have found 5-year overall survival rates of 52% after allogeneic HCT and 68.5% after autologous HCT. The total number of individuals studied is small and there is a lack of published controlled studies. La evidencia es insuficiente para determinar los efectos de esta tecnología en los resultados de salud.

Clinical input obtained from BCBSA in 2011, and national and international clinical guidelines support the use of autologous HCT as salvage therapy for individuals with chemosensitive Waldenström macroglobulinemia. Therefore, the evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Definiciones

NA

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 del miembro, 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: esta lista de códigos puede no ser exhaustiva y los códigos están 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

Cubierto cuando es médicamente necesario

Referencias

1. Kyriakou C, Canals C, Sibon D, et al. High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. May 1, 2010;28(13):2227-2232. PMID 20368570.
2. Cornell RF, Bachanova V, D'Souza A, et al. Allogeneic transplantation for relapsed Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma. Biol Blood Marrow Transplant. Jan 2017;23(1):60-66. PMID 27789362.
3. Kyriakou C, Canals C, Cornelissen JJ, et al. Allogeneic stem-cell transplantation in patients with Waldenstrom macroglobulinemia: report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. Nov 20, 2010;28(33):4926-4934. PMID 20956626.
4. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma. Version 1.2023.
5. Kapoor P, Ansell SM, Fonseca R, et al. Diagnosis and management of Waldenstrom macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines 2016. JAMA Oncol. Sep 1, 2017;3(9):1257-1265. PMID 28056114.
6. Leblond V, Kastritis E, Advani R, et al. Treatment recommendations from the Eighth International Workshop on Waldenstrom's Macroglobulinemia. Blood. Sep 8, 2016;128(10):1321-1328. PMID 27432877.
7. Talaulikar D, Tam CS, Joshua D, et al. Treatment of patients with Waldenstrom macroglobulinaemia: clinical practice guidelines from the Myeloma Foundation of Australia Medical and Scientific Advisory Group. Intern Med J. Jan 2017;47(1):35-49. PMID 28076910.
8. Ansell SM. Epidemiology, Pathogenesis, Clinical Manifestations, and Diagnosis of Waldenström Macroglobulinemia. In: UpToDate Online Journal [serial online]. Waltham, MA: UpToDate; updated May 13, 2026. Literature review current through May 2026.
9. Ansell SM. Treatment and Prognosis of Waldenström Macroglobulinemia. UpToDate Online Journal [serial online]. Waltham, MA: UpToDate; updated May 22, 2026. Literature review current through May 2026.
10. Rodríguez-Doyágüez P, Motornaya-Morozova, Martínez-Miguel P, Castillo-Torres C, Toldos-González Ó, Gil-Fernández JJ. Monoclonal gammopathy of renal significance: An atypical presentation of Waldenström's disease. Clin Nephrol Case Stud. 2024;12:17-21. Published 2024 Feb 8. doi:10.5414/CNCS111200.
11. Sakurai M, Mori T, Uchiyama H, et al. Outcome of stem cell transplantation for Waldenström's macroglobulinemia: analysis of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) Lymphoma Working Group. Ann Hematol. 2020;99(7):1635-1642. doi:10.1007/s00277-020-04078-3.
12. Treon SP, Sarosiek S, Castillo JJ. How we use Genomics and BTK-Inhibitors in the Treatment of Waldenstrom Macroglobulinemia. Blood. Published online January 11, 2024. doi:10.1182/blood.2022017235.