RESUMO
Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.
Assuntos
Mieloma Múltiplo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Quimioterapia de Indução , Lenalidomida/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológicoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiplo , Qualidade de Vida , Mieloma Múltiplo/tratamento farmacológico , Humanos , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fenilalanina/uso terapêutico , Fenilalanina/análogos & derivados , Feminino , Masculino , Resistencia a Medicamentos Antineoplásicos , Resultado do Tratamento , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva , Pessoa de Meia-Idade , IdosoRESUMO
Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed.
Assuntos
Mieloma Múltiplo , Intervalo Livre de Progressão , Humanos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Ensaios Clínicos como Assunto , Neoplasia Residual , BiomarcadoresRESUMO
Understanding the impact of induction and maintenance therapy on patients' quality of life (QoL) is important for treatment selection. This study aims to compare patient-reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL-C 30 and QOL-MY20 questionnaires in the AGMT-02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health-related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross-sectional comparisons indicated a "slight" superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross-sectional comparisons revealed a "slight" improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with "slight" or "moderate" impairments in several QoL scales compared with the observation group.