Autologous Stem Cell Transplantation (AuSCT) for Multiple Myeloma

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It would be optimal if all three questions proposed by HCFA were responded to with well-designed, controlled clinical trials. However, given the low incidence and terminal nature of the disease, as well as a limited number of treatment options currently available to beneficiaries, we believe that the evidence is sufficient to justify a national decision to cover single AuSCT with certain limitations. The better-designed trials concentrate solely upon patients with newly diagnosed or responsive multiple myeloma. Within this sub-group of myeloma patients, the evidence demonstrates a statistically greater treatment benefit from HDT/AuSCT compared to standard chemotherapy. HDT/AuSCT in refractory multiple myeloma has the weakest evidence. The 1996 BC/BS TEC assessment conducted its review of newly diagnosed or responsive multiple myeloma separate from its review of refractory multiple myeloma. As stated above, TEC concluded that the available evidence demonstrated that HDT/AuSCT was at least as beneficial as standard chemotherapy, and could possibly be better in improving the health outcomes of newly diagnosed or responsive multiple myeloma patients. However, the technology assessment also concluded that the available data did not adequately demonstrate that HDT/AuSCT could improve the health outcomes of patients with refractory multiple myeloma. In addition, there does not appear to be a justification for such intensive intervention in patients with an extremely low tumor burden (usually Durie-Salmon Stage I). The IFM study, as well as other clinical trials, had limited AuSCT candidacy to those with Durie-Salmon Stage II or III patients. Therefore, HCFA has determined that coverage of AuSCT should be limited to Durie-Salmon stage II or III patients with newly diagnosed or responsive multiple myeloma. This would include those patients with previously untreated disease, those with at least a partial response to prior chemotherapy, and those in responsive relapse (using the same definition of partial response). Partial response is defined as a 50% decrease either in measurable paraprotein [serum and/or urine] or in bone marrow infiltration, sustained for at least one month Overall, the body of evidence on AuSCT indicates that organ function (cardiac, pulmonary, hepatic, and renal) must be adequate prior to transplantation. In order to tolerate the toxic effects of HDT and the stresses of AuSCT, major organ systems cannot be functionally impaired. For example, effective renal clearance is necessary to allow for the filtration of toxic chemotherapeutic by-products. However, given the inherent variability in evaluating the adequacy of cardiac, pulmonary, renal, and hepatic functioning, as previously illustrated, HCFA will not limit coverage by setting organ function standards, allowing this necessary physiological evaluation to be conducted according to community medical practice and individual patient tolerance assessment. Finally, although the April 2000 BC/BS TEC assessment concluded that the benefits of HDT/AuSCT are applicable to the Medicare population, evidence regarding the issue of age remains speculative. In fact, BC/BS’s conclusions were only relevant to the young-old (mid-sixties to mid-seventies). Safety and effectiveness of HDT/AuSCT in older age groups was not addressed. In reviewing the medical literature, HCFA discovered that the oldest multiple myeloma patient that received HDT/AuSCT was 76 (the oldest patient found during BC/BS TEC’s review was 77). However, it is unclear just how many patients over age 75 were actually studied. The IFM trial, which presented the most convincing evidence regarding the medical effectiveness of HDT/AuSCT, also used age to limit eligibility. Due to the lack of available evidence on those multiple myeloma patients over age 75 and the well-understood hazards of the procedure which seem to be greater with advancing age, HCFA feels compelled to limit coverage of AuSCT to the young-old Medicare population by setting an upper age limit of 77. We believe that such a limitation is reasonable because (1) no multiple myeloma patients over age 77 were analyzed and (2) the median age at diagnosis is 65 years. At the present time, it is not reasonable and necessary to cover AuSCT in those patients above age 77. HCFA will await further data on elderly multiple myeloma patients, such that any future age limits can be better supported by an evidentiary approach. In conclusion, HCFA has decided to issue a national coverage determination for AuSCT in the treatment of multiple myeloma that will reflect these limitations: Single AuSCT is only covered for Durie-Salmon stage II or III patients that fit the following requirements: Newly diagnosed or responsive multiple myeloma. This includes those patients with previously untreated disease, those with at least a partial response to prior chemotherapy (defined as a 50% decrease either in measurable paraprotein [serum and/or urine] or in bone marrow infiltration, sustained for at least one month), and those in responsive relapse; Adequate cardiac, renal, pulmonary, and hepatic function; and Age ≤ 77 years. Due to insufficient evidence, at this time, tandem transplantation for multiple myeloma remains non-covered. As new evidence requires, we will reconsider this decision. At present, all other uses of AuSCT for multiple myeloma are not covered.