RESUMEN
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.
RESUMEN
Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.
Asunto(s)
Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Quimioterapia de Inducción , Lenalidomida/uso terapéutico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológicoRESUMEN
INTRODUCTION: Targeting the B cell receptor (BCR) pathway via ibrutinib, a specific inhibitor of Bruton's tyrosine kinase, has shown marked clinical efficacy in treatment of patients with chronic lymphocytic leukemia (CLL), thus becoming a preferred first line option independent of risk factors. However, acquired resistance to ibrutinib poses a major clinical problem and requires the development of novel treatment combinations to increase efficacy and counteract resistance development and clinical relapse rates. CASE PRESENTATION: In this study, we performed exome and transcriptome analyses of an ibrutinib resistant CLL patient in order to investigate genes and expression patterns associated with ibrutinib resistance. Here we provide evidence that ibrutinib resistance can be attributed to aberrant mammalian target of rapamycin (MTOR) signaling. CONCLUSION: Thus, our study proposes that combined use of MTOR inhibitors with ibrutinib could be a possible option to overcome therapy resistance in ibrutinib treated patients.