Stem cell treatment for multiple myeloma

This review discusses the efficacy of stem cell transplantation in the treatment of multiple myeloma and its role in the era of novel drugs and treatment modalities.

Advances in the management of toxicity and improved GVHD prophylaxis have allowed allo-SCT to be used in the treatment of relapsed and refractory multiple myeloma (RRMM), especially in patients who have already undergone prior ASCT.

In addition, progress has been made on the role of allogeneic stem cell transplantation (allo-SCT) in relapsed/refractory settings in the era of combination of novel agents. In addition, significant benefit with transplantation at relapse in patients who were initially treated with conventional chemotherapy raised the question of early versus delayed ASCT. This has been thought to be partly related to the patient selection criteria and different conditioning therapy in the trials. Although transplantation improved the response rate and progression-free survival, there was no overall survival benefit in most of the trials. An important finding from these studies was a significant increase in complete remission with ASCT, results that translated into significantly prolonged progression-free survival (PFS) and overall survival (OS). In addition, some studies have tried to evaluate the role of novel agents as part of maintenance therapy post ASCT. Hence, these agents may offer another means of overcoming drug resistance. It has, however, been shown that agents such as thalidomide, bortezomib, and lenalidomide act not only on myeloma cells, but also on the tumor microenvironment. The efficacy of high-dose chemotherapy is mostly related to damage to tumor-cell DNA. Strategies to modulate the graft-versus-host disease (GVHD) while maintaining or improving the graft-versus-myeloma (GVM) effect could place allogeneic SCT back in the treatment armamentarium of MM. Allogeneic SCT is one potentially curative option for MM, albeit with an increased risk of death due to high TRM. Auto-SCT has the advantages of resetting the bone marrow microenvironment, short-lived toxicity compared to the long-term physical and financial toxicities of continued chemotherapy in the absence of SCT, very low transplant-related mortality (TRM) in high volume centers, and providing longer disease-free survival when followed by maintenance therapy. Tandem auto-SCT followed by maintenance has shown a progression-free survival (PFS) benefit in high-risk MM, and hence can be considered in young and fit patients with high-risk disease. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients.

Stem cell treatment for multiple myeloma