ABSTRACT
Choice of treatment for newly diagnosed transplant-ineligible multiple myeloma poses a difficult task due to an ever-increasing plethora of different regimens. Attempting to clarify this subject, we performed a systematic review and Bayesian network meta-analysis of 29 randomized clinical trials, enrolling 14,533 patients, and comparing 25 different treatment regimens regarding overall survival(OS), progression-free survival(PFS), complete response(CR), overall response rate(ORR) and toxicity. Head-to-head comparisons for all regimens and ranking of best treatments are reported. OS analysis showed superiority of lenalidomide(R) and bortezomib(V) containing regimens over thalidomide(T) protocols (e.g. Rd/CTD-HR:0.7;95%CrI:0.53-0.93, VMP/TD-HR:95%0.45;CrI:0.29-0.69). Concerning PFS, daratumumab(D) plus V (Dara-VMP) showed superior results over R (e.g. Dara-VMP/MPR-HR:0.52;95%CrI:0.34-0.77), V plus T (Dara-VMP/VTd-HR:0.56;95%CrI:0.37-0.65) and T (Dara-VMP/CTD-HR:0.34;95%CrI:0.23-0.49) containing regimens. Also, VRd and VMPT-VT performed well over other regimens. Dara-VMP showed superior response rates over R (ORR Dara-VMP/MPR-RR:6.27;95%CrI:2.18-18.95, CR Dara-VMP/MPR-RR:1.53;95%CrI:1.21-1.96) and T (ORR Dara-VMP/MPT-T-RR:4.05;95%CrI:1.19-13.26, CR Dara-VMP/MPT-T-RR:1.42;95%CrI:1.09-1.85; ORR Dara-VMP/CTD-RR:2.72;95%CrI:1.2-6.31, CR Dara-VMP/CTD-RR:1.2;95%CrI:1.05-1.36) including a higher rate of complete remission even when compared to VRd (RR:1.29;95%CrI:1.01-1.66). A higher rate of grade 3-4 adverse events was found for RD and CPR (thrombotic); VTd, VTP and VMPT-VT (neurological); RD and VAD (infectious); MPR-R and VAD (hematological); Vd and VTd (gastrointestinal); VAD, VMPCc and RD (cardiovascular). These results confirm obsolescence of classical regimens (such as VAD and MP) while pointing out benefits in efficacy resulting from incorporation of quadruplets and triplets combining new agents (Dara-VMP, VRd and VMPT-VT) and supports current rational of treatment until progression or prohibitive toxicity, especially when including lenalidomide. Based on this data, we would recommended incorporation of strategies combining novel agents (monoclonal antibodies, immunomodulatory imide drugs and proteasome inhibitors) in triplets or quadruplets and/or those comprising long term use of lenalidomide as standard frontline treatments. Moreover, this study settles daratumumab's place as an attractive alternative for upfront treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Antibodies, Monoclonal/administration & dosage , Bayes Theorem , Bortezomib/administration & dosage , Disease-Free Survival , Humans , Lenalidomide/administration & dosage , Network Meta-Analysis , Randomized Controlled Trials as Topic , Thalidomide/administration & dosage , Treatment OutcomeABSTRACT
INTRODUCTION: The Informed Consent allows the person invited to participate of a research project to understand the procedures, risks, discomforts, benefits and rights involved; determining an autonomic decision. We want to verify in the informed consent process the adequacy of given information to research subjects in a collective way. METHODS: A research project was chosen from the gynecologic area. The collective obtainment consisted of an oral presentation. After that, The Consent form was shown. Forty-five patients were interviewed, immediately after the consent obtainment. RESULTS: Remembrance capacity of information about procedures, risks and benefits explained were verified. All participants (100%) remembered the procedures, 54% of them remembered the risks and 96% the probable benefits. Comparing these data with others from a similar study using conventional informed consent process (individual information transmission) the subjects remember more information in the present study. CONCLUSION: These results evidence the possibility to inform collectively the research subjects when getting the Informed Consent in those projects where this choice is available.
Subject(s)
Biomedical Research , Informed Consent , Comprehension , Female , Humans , Research Design , Risk AssessmentABSTRACT
Objetivos: O processo de consentimento livre e esclarecido tem por objetivo permitir que a pessoa que está sendo convidada a participar de um projeto de pesquisa compreenda os procedimentos, riscos, desconfortos, benefícios e direitos envolvidos, visando permitir uma decisão autônoma. O objetivo do presente estudo foi avaliar a possibilidade de fornecer informações de forma coletiva na obtenção do consentimento livre e esclarecido. MÉTODOS: Em um projeto de pesquisa da área da Ginecologia foi utilizada a transmissão coletiva de informações, através de uma palestra, para a obtenção do consentimento livre e esclarecido. Foram entrevistadas 45 participantes deste projeto, verificando a recordação dos procedimentos, riscos e benefícios. RESULTADOS: Todas as participantes (100 por cento) recordaram os procedimentos, 54 por cento delas recordaram os riscos e 96 por cento os benefícios prováveis. Comparando os presentes resultados com os obtidos em um estudo similar utilizando o processo de consentimento livre e esclarecido convencional (transmissão individual de informações), verificou-se que os sujeitos de pesquisa recordaram mais informações no atual estudo. CONCLUSÕES: Estes resultados indicam a possibilidade de que as informações necessárias ao consentimento livre e esclarecido possam ser dadas de forma coletiva, nos projetos em que esta alternativa seja adequada
