191 Form

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Medical Policy Hematopoietic Cell Transplantation for Miscellaneous Solid Tumors in Adults Table of Contents • Policy: Commercial • Description
• References • Policy: Medicare • Policy History
• Coding Information • Authorization Information • Information Pertaining to All Policies

Policy Number: 191

BCBSA Reference Number: 8.01.24 (For Plan internal use only) NCD/LCD: NA Related Policies
• Hematopoietic Cell Transplantation for Solid Tumors of Childhood, #208
• Hematopoietic Cell Transplantation in the Treatment of Germ Cell Tumors, #247 • Hematopoietic Cell Transplantation for CNS Embryonal Tumors and Ependymoma, #205 • Hematopoietic Cell Transplantation for Epithelial Ovarian Cancer, #204 Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity
Medicare HMO BlueSM and Medicare PPO BlueSM Members

Autologous or allogeneic cell transplant is INVESTIGATIONAL for the following malignancies in adults: • Lung cancer, any histology
• Colon cancer
• Rectal cancer
• Pancreas cancer
• Stomach cancer
• Esophageal cancer
• Gall bladder cancer
• Cancer of the bile duct
• Renal cell cancer
• Cervical cancer
• Uterine cancer
• Cancer of the fallopian tubes
• Prostate cancer
• Nasopharyngeal cancer
• Paranasal sinus cancer

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• Neuroendocrine tumors
• Soft tissue sarcomas
• Thyroid tumors
• Tumors of the thymus
• Tumors of unknown primary origin, or • Malignant melanoma.

Prior Authorization Information
Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.
Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

Outpatient Commercial Managed Care (HMO and POS) This is not a covered service. Commercial PPO and Indemnity This is not a covered service. Medicare HMO BlueSM This is not a covered service. Medicare PPO BlueSM This is not a covered service.

CPT Codes / HCPCS Codes / ICD Codes Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

The following codes are included below for informational purposes only; this is not an all-inclusive list. According to the policy statement above, the following CPT codes are considered investigational for the conditions listed for Commercial Members: Managed Care (HMO and POS), PPO, Indemnity, Medicare HMO Blue and Medicare PPO Blue: CPT Codes CPT codes:

Code Description 38241 Hematopoietic progenitor cell (HPC); autologous transplantation HCPCS Codes HCPCS codes: Code Description S2142 Cord blood derived stem-cell transplantation, allogeneic S2150 Bone marrow or blood-derived peripheral stem-cell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical surgical, diagnostic and emergency services)

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Description Though cancer incidence along with overall mortality has been declining in the United States, certain population groups continue to have an increased risk of cancer progression and mortality due to social, economic, and environmental disadvantages.1, The National Cancer Institute has published statistics on cancer disparities in relation to various criteria including specific racial and ethnic groups, gender, and geography. Some key incidence and mortality statistics in the United States are as follows: incidence rates of lung, colorectal, and cervical cancers are increased in rural Appalachia compared to urban areas; American Indians/Alaska Natives have increased mortality rates from kidney, liver, and intrahepatic bile duct cancer compared to other racial and ethnic groups; Black men are twice as likely to die of prostate cancer than White men.

Hematopoietic Cell Transplantation HCT is a procedure in which hematopoietic stem cells are intravenously infused to restore bone marrow and immune function in cancer patients who receive bone marrow-toxic doses of cytotoxic drugs with or without whole-body radiotherapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or a donor (allogeneic HCT [allo-HCT]). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates.

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HCT. In allogeneic stem cell transplantation, immunologic compatibility between donor and patient is a critical factor for achieving a successful outcome. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. HLA refers to the gene complex expressed at the HLA-A, -B, and -DR (antigen-D related) loci on each arm of chromosome six. An acceptable donor will match the patient at all or most of the HLA loci.

Conditioning for HCT

Conventional Conditioning The conventional (“classical”) practice of allo-HCT involves the administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to cause bone marrow ablation in the recipient. The beneficial treatment effect of this procedure is due to a combination of the initial eradication of malignant cells and subsequent graft-versus-malignancy effect mediated by non-self-immunologic effector cells. While the slower graft-versus-malignancy effect is considered the potentially curative component, it may be overwhelmed by existing disease in the absence of pretransplant conditioning. Intense conditioning regimens are limited to patients who are sufficiently medically fit to tolerate substantial adverse effects. These include opportunistic infections secondary to loss of endogenous bone marrow function and organ damage or failure caused by cytotoxic drugs. After graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and graft- versus-host disease (GVHD), which increases susceptibility to opportunistic infections. The success of autologous HCT is predicated on the potential of cytotoxic chemotherapy, with or without radiotherapy, to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of the bone marrow with normal hematopoietic stem cells obtained from the patient before undergoing bone marrow ablation. Therefore, autologous HCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HCT are also susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not GVHD. Reduced-Intensity Conditioning Allo-HCT Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses of cytotoxic drugs or less intense regimens of radiotherapy than are used in traditional full-dose myeloablative conditioning treatments. Although the definition of RIC is variable, with numerous versions employed, all regimens seek to balance the competing effects of relapse due to residual disease and non-relapse mortality. The goal of RIC is to reduce disease burden and to minimize associated treatment-related morbidity and non-

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relapse mortality in the period during which the beneficial graft-versus-malignancy effect of allogeneic transplantation develops. RIC regimens range from nearly total myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allo-HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full donor chimerism. In this review, the term RIC will refer to all conditioning regimens intended to be nonmyeloablative. HCT in Solid Tumors in Adults HCT is an established treatment for certain hematologic malignancies. Its use in solid tumors is less well established, although it has been investigated for a variety of solid tumors. With the advent of nonmyeloablative allogeneic transplant, interest has shifted to exploring the generation of alloreactivity to metastatic solid tumors via a graft-versus-tumor effect of donor-derived T cells.1,

HCT as a treatment for ovarian cancer, germ cell tumors, ependymoma, or malignant glioma is addressed separately (see policy #204, #247,and #205, respectively). HCT as a treatment for breast cancer is not addressed. This evidence review collectively addresses other solid tumors of adults for which HCT has been investigated, including lung cancer, malignant melanoma, tumors of the gastrointestinal tract (affecting the colon, rectum, pancreas, stomach, esophagus, gallbladder, or bile duct), male and female genitourinary systems (eg, renal cell carcinoma, prostate cancer, cervical cancer, uterine cancer, fallopian tube cancer), tumors of the head and neck, soft tissue sarcoma, thyroid tumors, tumors of the thymus, and tumors of unknown primary origin.

Summary Hematopoietic cell transplantation (HCT) is an established treatment for certain hematologic malignancies and has been investigated for a variety of adult solid tumors. Interest continues in exploring nonmyeloablative allogeneic HCT (allo-HCT) for a graft-versus-tumor effect of donor-derived T-cells in metastatic solid tumors.

Autologous Hematopoietic Cell Transplantation For individuals who have adult soft tissue sarcomas who receive autologous hematopoietic cell transplantation (HCT), the evidence includes 2 randomized controlled trials (RCTs), phase 2 single-arm studies (some of which have been summarized in a systematic review), and a retrospective registry study. Relevant outcomes are overall survival (OS), disease-specific survival, and treatment-related mortality and morbidity. Although a phase 2 RCT reported longer survival for patients treated with autologous HCT than with standard chemotherapy, this trial did not show an overall survival benefit with HCT. An RCT from 2019 also showed no survival benefits with autologous HCT. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. For individuals who have small cell lung cancer who receive autologous HCT, the evidence includes several RCTs, and systematic reviews of these studies. Relevant outcomes are OS, disease-specific survival, and treatment-related mortality and morbidity. Studies have not reported increased OS for patients with small-cell lung cancer treated with autologous HCT. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Allogeneic Hematopoietic Cell Transplantation For individuals who have renal cell carcinoma, colorectal cancer, pancreatic cancer, or nasopharyngeal cancer who receive allogeneic-HCT (allo-HCT), the evidence includes single-arm series. Relevant outcomes are OS, disease-specific survival, and treatment-related mortality and morbidity. The evidence for allo-HCT to treat renal cell carcinoma, colorectal cancer, pancreatic cancer, and nasopharyngeal cancer has been limited to case series. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. Policy History Date Action

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10/2025 Coding information clarified 3/2025 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 3/2024 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 3/2023 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 2/2022 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 10/2021 Clarified coding information 3/2021 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 1/2021 Coding information clarified 10/2020 Coding information clarified 2/2020 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 3/2019 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 1/2019 Outpatient prior authorization is required for all commercial products including Medicare Advantage. Effective 1/1/2019. 2/2018 Annual policy review. New references added. 3/2017 Annual policy review. Title changed. New references added.
10/2016 Clarified coding information.
3/2016 Annual policy review. New references added. 12/2014 Annual policy review. New references added. 6/2014 Updated Coding section with ICD10 procedure and diagnosis codes, effective 10/2015. 11/2011-4/2012 Medical policy ICD 10 remediation: Formatting, editing and coding updates.
No changes to policy statements.
7/2011 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 9/2010 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 6/1/2010 Medical policy 191 effective 6/1/2010 describing ongoing non-coverage Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines

References

1. Cancer disparities. National Cancer Institute. https://www.cancer.gov/about- cancer/understanding/disparities. Published March 21, 2024. Accessed November 19, 2024.
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3. American Cancer Society. Key statistics for soft tissue sarcomas. https://www.cancer.org/cancer/types/soft-tissue-sarcoma/about/key-statistics.html. Updated January 12, 2023. Accessed November 19, 2024.
4. National Comprehensive Cancer Network (NCCN). Soft tissue sarcoma. Version 3.2024. http://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed November 17, 2024.

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5. Pedrazzoli P, Ledermann JA, Lotz JP, et al. High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol. Oct 2006; 17(10): 1479-88. PMID 16547069
6. Kasper B, Dietrich S, Mechtersheimer G, et al. Large institutional experience with dose-intensive chemotherapy and stem cell support in the management of sarcoma patients. Oncology. 2007; 73(1- 2): 58-64. PMID 18334832
7. Schlemmer M, Wendtner CM, Falk M, et al. Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas. Oncology. 2006; 71(1-2): 32-
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10. Bui-Nguyen B, Ray-Coquard I, Chevreau C, et al. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial. Ann Oncol. Mar 2012; 23(3): 777-784. PMID 21652583
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12. Dirksen U, Brennan B, Le Deley MC, et al. High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. J Clin Oncol. Dec 01 2019; 37(34): 3192-3202. PMID 31553693
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14. Hartmann JT, Horger M, Kluba T, et al. A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high dose ICE consolidation with PBSCT in non-resectable, high grade, adult type soft tissue sarcomas. Invest New Drugs. Dec 2013; 31(6): 1592-601. PMID 24091981
15. Heilig CE, Badoglio M, Labopin M, et al. Haematopoietic stem cell transplantation in adult soft-tissue sarcoma: an analysis from the European Society for Blood and Marrow Transplantation. ESMO Open. Oct 2020; 5(5): e000860. PMID 33097652
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23. National Comprehensive Cancer Network (NCCN). Kidney cancer. Version 2.2025. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed November 18, 2024.
24. Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. Sep 14 2000; 343(11): 750-8. PMID 10984562
25. Bregni M, Bernardi M, Servida P, et al. Long-term follow-up of metastatic renal cancer patients undergoing reduced-intensity allografting. Bone Marrow Transplant. Aug 2009; 44(4): 237-42. PMID 19234510
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28. Abe Y, Ito T, Baba E, et al. Nonmyeloablative allogeneic hematopoietic stem cell transplantation as immunotherapy for pancreatic cancer. Pancreas. Oct 2009; 38(7): 815-9. PMID 19696692
29. Omazic B, Ayoglu B, Löhr M, et al. A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer. J Immunother. May 2017; 40(4): 132-139. PMID 28338506
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31. Omazic B, Remberger M, Barkholt L, et al. Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation for Solid Cancer. Biol Blood Marrow Transplant. Apr 2016; 22(4): 676-681. PMID 26740375
32. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. Nov 2015; 21(11): 1863-1869. PMID 26256941
33. Kanate AS, Majhail NS, Savani BN, et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. Jul 2020; 26(7): 1247-1256. PMID 32165328
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