High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years

Abstract

One or two cycles of high-dose chemotherapy with autologous hematopoietic stem cell transplantation have been shown to improve response rates and survival in myeloma. While this observation has largely been made in patients under the age of 65 years, there is evidence to suggest that the conclusions can be extrapolated to older individuals as well. In contrast to other hematologic malignancies treated with high-dose therapy, autografted myeloma patients continue to relapse several years after transplantation, and few patients are cured with this modality. However, up to a third of patients may be alive beyond a decade; some with excellent quality of life giving rise to the concept of 'operational cure'. Relapsing disease can be treated with novel agents or repeat high-dose chemotherapy and transplantation. The pressing questions to which answers are not obvious at the moment are whether tandem transplantation should be offered to all patients, and whether novel agents should be used before transplantation or reserved for relapse. Despite their excellent activity, there is no evidence so far that novel agents such as thalidomide, bortezomib and lenalidomide can replace high-dose chemotherapy and stem cell transplantation.

Impact of early relapse after auto-SCT for multiple myeloma

“…The result presented here confirms previous observations regarding duration of response after first SCT. [32][33][34] Clearly these patients derive little benefit from conventional salvage therapies, to which they become resistant rapidly, as highlighted by the median survival of only 10.8 months from the time they relapse. It is interesting that patients who were treated with at least one of the novel agents (thalidomide, bortezomib or lenalidomide) appeared to have some improvement in their median survival post transplant; 15 months vs 5 months for the rest.…”

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

“…1 Thus, long-term follow-up studies in the setting of high dose therapy/ autologous stem cell transplantation show that only a small fraction of MM patients (6-18%) remain relapse free for 10 years or more, and these patients are now considered as being operationally cured. [2][3][4] Interestingly, this operational cure is not restricted to patients in complete response, since those who revert to having a monoclonal gammopathy of undetermined significance (MGUS)-like profile may also achieve long-term disease control (LTDC), despite persistence of a residual M-component. 4 Recent clinical and molecular data suggest that some features may help to identify this group of LTDC-MM patients such as an evolving smoldering pattern, a gene expression profile signature of MGUS and the CD2 molecular subtype.…”

Second auto-SCT for treatment of relapsed multiple myeloma

“…1 The use of high-dose chemotherapy with auto-SCT improves the response rates and the survival outcomes for patients with MM. 2 Several studies support the use of auto-SCT in the front-line setting or at relapse and are considered as a standard of care for eligible patients. 3,4 Unfortunately, patients eventually suffer disease relapse after auto-SCT and require salvage therapy.…”