How to treat elderly patients with multiple myeloma: combination of therapy or sequencing.
Patients with multiple myeloma aged older than 65 years have traditionally received an oral regimen combining melphalan and prednisone (MP). The introduction of novel agents, such as immunomodulatory drugs and proteasome inhibitors, has substantially changed the treatment paradigm of this disease. Five randomized phase III studies, comparing MP plus thalidomide (MPT) versus MP, have shown that MPT increased time to progression (TTP); however, only two of these five studies showed improvement in overall survival (OS). One randomized study has shown that MP plus bortezomib (MPV) increases both TTP and OS compared with MP. Both MPT and MPV are now regarded as the new standards of care for elderly patients. Other promising results have been reported with MP plus lenalidomide or lenalidomide plus dexamethasone, or the combination of cyclophosphamide, thalidomide, and dexamethasone. Reduced-intensity transplantation can be an option for some patients, especially when novel agents are incorporated into pre-transplant induction and post-transplant consolidation. For patients aged older than 75 years a gentler approach should be used, and doses of standard MPT or MPV should be reduced. An accurate management of treatment-related adverse events with prompt dose-reduction can greatly reduce the rate of early discontinuation and significantly improve treatment efficacy. The choice of treatment should be tailored according to the patient's biologic age and comorbidities, and the expected toxicity profile of the regimen.
Palumbo
Antonio
A
Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera Universitaria S. Giovanni Battista, Torino, Italy. appalumbo@yahoo.com
Gay
Francesca
F
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000628:therapy; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003131:Combined Modality Therapy; D015897:Comorbidity; D019468:Disease Management; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000188:drug therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D020246:Venous Thrombosis / Q000139:chemically induced
D001897:Boronic Acids; D019653:Myeloablative Agonists; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide