Management Strategies for Relapsed/Refractory Multiple Myeloma: Current Clinical Perspectives
Section snippets
Chemotherapy and Transplant
In the relapsed/refractory setting, conventional or high-dose chemotherapy has been a longstanding approach to salvage treatment. Regimens have included high-dose melphalan; high-dose methylprednisolone; high-dose dexamethasone; vincristine, doxorubicin, and pulsed high-dose dexamethasone (VAD); vincristine, melphalan, cyclophosphamide, and prednisone (VMPC) alternating with vincristine, carmustine, doxorubicin, and prednisone (VBAP); doxorubicin, vincristine, dexamethasone, etoposide, and
Incidence and Management of Treatment-Related Adverse Events
The established novel agents have different and specific toxicity profiles, which, along with patients' characteristics and comorbidities, should be considered when choosing a treatment regimen. In most cases, the adverse events (AEs) associated with these agents can be managed with patient monitoring, supportive care, and dose reduction and interruption where appropriate. Additional management strategies may also be appropriate for patients aged ≥75 years.
Adjunctive/Supportive Care
Important advances have occurred in adjunctive treatment and supportive care available for patients with MM. Approximately 85% of patients develop bone disease in the form of diffuse osteopenia and/or osteolytic lesions, and the related complications (eg, bone pain and pathologic fractures) are a major cause of deteriorating quality of life and performance status.11 Treatment of bone pain should start with non-opioid analgesics such as acetaminophen; however, nonsteroidal anti-inflammatory
Implications of Genetic Heterogeneity
MM is a disease with marked genetic heterogeneity, which has important implications for treatment because molecular subgroups respond differently to currently available regimens. Chromosomal abnormalities are detected with conventional cytogenetics or fluorescence in situ hybridization (FISH) in >90% of patients, and include deletions, trisomies, and translocations.141 Patients with hyperdiploid and t(11;14) mutations have standard-risk disease and typically respond well to conventional
Conclusions
In recent years, the introduction of thalidomide, lenalidomide, and bortezomib has changed the treatment paradigm for patients with relapsed/refractory MM and dramatically improved clinical outcome compared with conventional chemotherapy alone. However, not all patients will respond to established novel agents, and even those who do respond will eventually relapse or become refractory to treatment, owing in part to the changing biology of the tumor and development of drug-resistant phenotypes
Acknowledgment
The author wishes to acknowledge Marithea Goberville, PhD, Tristin Abair, PhD, and Trudy Grenon Stoddert, ELS, for their assistance in preparing the manuscript for publication.
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Cited by (33)
American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma
2015, Biology of Blood and Marrow TransplantationTherapy of relapsed and refractory plasma cell myeloma in Polish population - Analysis
2015, Acta Haematologica PolonicaMeta-analysis of the efficacy and safety of bortezomib Re-treatment in patients with multiple myeloma
2014, Clinical Lymphoma, Myeloma and LeukemiaCitation Excerpt :Almost all patients with MM who survive initial treatment will eventually have progression of disease and require further therapy. The spectrum of treatment options available for relapsed and/or refractory MM has dramatically broadened over the past 10 years, largely because of the introduction of the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and proteasome inhibitors including bortezomib and carfilzomib.3,4 The choice of treatment for patients with relapsed and/or refractory MM depends on a number of disease-related, regimen-related, and patient-related factors.1,2,4,5
Autologous Stem Cell Transplantation: An Effective Salvage Therapy in Multiple Myeloma
2013, Biology of Blood and Marrow TransplantationCitation Excerpt :Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT (Table 4). Currently, there is no broadly accepted standard treatment for patients with relapsed/refractory MM [21]. For the selection of an appropriate treatment strategy at this stage, both disease-related and patient-related factors and, importantly, the type of previous therapy need to be considered [21-25].
Conflicts of interest: Dr Jakubowiak has received consulting fees from Bristol-Myers Squibb, Celgene, Millennium Pharmaceuticals, and Onyx Pharmacetuicals. He is also a member of the speakers' bureau for Celgene.
Publication of this supplement was supported by Onyx Pharmaceuticals.