Autologous Stem Cell Transplantation (AuSCT) for Amyloidosis

The medical literature now provides convincing evidence that chemotherapy and AuSCT produces hematologic and clinical remissions, enhances quality of life, and results in long survival of patients with AL amyloidosis regardless of age. We are pleased that based on review of this literature, the Centers for Medicare and Medicaid Services (CMS) has proposed coverage of AuSCT for patients with AL amyloidosis. We would like to comment upon some of the details of the draft proposal.

CMS proposes to limit coverage to patients with amyloid deposition in two or fewer organs, serum creatinine <2.0 mg/dl, and cardiac LVEF >55%. The organ-based limitation in eligibility for high dose chemotherapy and autologous stem cell transplantation is not as yet supported by clinical data. The expert opinion cited in the CMS draft proposal, Gertz and Comenzo, Blood 2002, proposes a risk-adapted approach to treatment of AL amyloidosis that is now being studied prospectively at one of the author’s centers. In the analysis of factors affecting survival in our large series of patients undergoing AuSCT for AL amyloidosis, cardiac involvement and conditioning dose of chemotherapy were the only clinical factors that negatively affected survival, although age, performance status, and time from diagnosis to referral indirectly affected survival by affecting the dose regimen (Skinner et al., Annals 2004). In another study from our center, 15 patients who had end stage renal disease (ESRD) at the time of AuSCT were found to have hematologic responses, survival outcomes and treatment- related mortality that was not significantly different from those of patients without renal disease (Casserly et al., Kidney Int 2003). Thus, so far there is no evidence- based justification for limiting AuSCT for patients other than those with reduced cardiac function. Transplants should be limited to patients without clinically significant congestive heart failure and with left ventricular EF >45%. Eligibility for AuSCT should otherwise be determined by the treating physician based upon appropriate criteria which might include clinical practice and experience, analysis of risk- benefit ratio determined in cooperation with the individual patient, or clinical trials eligibility criteria set with approval of the local IRB,.

A critical component omitted from the draft proposal is the establishment of strict diagnostic criteria for AL amyloidosis. Without strict diagnostic criteria, some non-AL patients with systemic amyloidosis could be incorrectly diagnosed with AL and treated inappropriately (see Lachman et al., NEJM 2002). Minimum diagnostic criteria should include: A. histologic diagnosis of systemic amyloid disease by appropriate tissue biopsy; B. evidence of clonal plasma cell disorder by bone marrow immunohistochemistry and/or demonstration of monoclonal protein in serum or urine; and C. absence of evidence of hereditary or secondary amyloidosis by family history and clinical presentation.

With these caveats, we are extremely grateful to CMS for reviewing their policy towards treatment of patients with AL amyloidosis. Wider availability of HDM/AuSCT treatment for AL amyloidosis currently represents the best hope for successful treatment of patients with this life- threatening disorder.

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To whom it may concern:

I am writing on behalf of the Amyloidosis Support Network (ASN), a not-for-profit 501(c)(3) all volunteer organization. We are the world’s only organization dedicated to amyloidosis patient advocacy, support and medical community awareness.

Currently section 110.8.1 of the National Coverage Determination (NCD) manual (CIM §35-30) states that the Autologous stem cell transplantation (AuSCT) procedure for primary AL amyloidosis has a national non-coverage determination for Medicare beneficiaries 64 years of age or older.

The ASN is in strong agreement with the March 30, 2004, formal request for reconsideration provided by Legacy Good Samaritan Hospital and the July 26, 2004 comments from the Dana Farber Cancer Institute in support of coverage for coverage of AuSCT for AL Amyloidosis. Data presented by Boston University School of Medicine, Mayo Clinic, Washington University, and the ABMTR conclude that AuSCT offers improvement in overall survival for patients age 65 and over and therefore would provide significant life- prolonging benefit to applicable patients in the Medicare population.

Moreover, the ASN would to add two additional points as background for our comments:

1. We agree with one of President Bush’s health care policies where he stated on various occasions “Give patients and doctors – not government bureaucrats – more control over health care decisions”.
2. Also, the AuSCT procedure for Multiple Myeloma, a closely related “sister disease” to AL Amyloidosis, is covered for Medicare beneficiaries 64 years of age or older. We do not understand how Medicare justifies this discriminatory practice.

In reference to the December 15, 2004, Draft Decision Memo for AuSCT for Amyloidosis (CAG- 00050R), the ASN believes it is directionally correct. As we see it, the draft contains 2 operative components; the criteria for coverage and the registry.

The ASN fully supports the registry concept and would be willing to provide what we can do as a patient advocacy organization to make it a reality. This might include infrastructure and/or procedures. We understand that the registry would not be a requirement for coverage, but we believe the CMS has an opportunity to help improve, refine and contribute to the body of knowledge on the diagnosis, treatment and management of AL Amyloidosis. In addition, we recommend the CMS expand the registry concept to incent and otherwise encourage patients to participate in clinical trials. This inevitably will serve to provide the following benefits: