RESUMO
PURPOSE: Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression. PATIENTS AND METHODS: Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS. RESULTS: The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms. CONCLUSION: Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Lenalidomida/administração & dosagem , Mieloma Múltiplo/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Quimioterapia de Consolidação , Dexametasona/efeitos adversos , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lenalidomida/efeitos adversos , Quimioterapia de Manutenção , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Agonistas Mieloablativos/administração & dosagem , Intervalo Livre de Progressão , Estudos Prospectivos , Indução de Remissão , Reoperação , Fatores de Tempo , Transplante Autólogo , Estados Unidos , Adulto JovemRESUMO
Abstract Several autoimmune disorders have been associated with a variety of hematopoietic malignancies, particularly lympho-proliferative disorders. Multiple myeloma (MM) is one of the most common hematologic malignancies and has been described in the context of a variety of autoimmune conditions. Due to their diversity and rarity, the clinical features of autoimmune conditions associated with MM have not been elucidated and the pathogenesis remains unclear. In this report, we describe two cases of autoimmune conditions in the setting of MM and review the current literature.
Resumen Varios trastornos autoinmunes se han asociado a una variedad de neoplasias malignas hematopoyéticas, particularmente trastornos linfoproliferativos. El mieloma múltiple (MM) es una de las neoplasias malignas hematológicas más comunes y ha sido descrito en el contexto de una variedad de condiciones autoinmunes. Debido a su diversidad y rareza, las características clínicas de las condiciones autoinmunes asociadas con el MM no han sido aclaradas y la patogénesis sigue siendo poco clara. En este artículo se describen dos casos de condiciones autoinmunes en el marco del MM y se realiza una revisión de la literatura actual.