Frontline treatment for transplant-eligible multiple myeloma: A 6474 patients network meta-analysis.

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post-transplant results. Therefore, best frontline treatment for transplant-eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta-analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide-lenalidomide-dexamethasone) over TD-based (thalidomide-dexamethasone, HR = 0.76,0.62-0.90), VAD-based (HR = 0.71,0.52-0.90), and Z-Dex (idarubicin-dexamethasone, HR = 0.37,0.17-0.76) regimens. Concerning PFS, VTD (bortezomib-thalidomide-dexametasone) showed superior results when compared with TD-based (HR = 0.66,0.51-0.84), VAD-based (HR = 0.61,0.46-0.82), Z-Dex (HR = 0.42,0.22-0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41-0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide-only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide-doxorubicin-dexamethasone), neurological with PAD (bortezomib-doxorubicin-dexamethasone), infectious with Dex, hematological with Z-Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant-eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression-free survival, when compared with bortezomib/thalidomide protocols.

Conventional and high-dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta-analysis of 7258 patients.

Previous meta-analyses suggested that acute myeloid leukaemia induction regimens containing idarubicin (IDA) or high-dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional-dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta-analysis regarding these three regimens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02-1.26] and IDA (RR 1.13; 95% CrI 1.05-1.23) showed higher CR rates than CDD. IDA also led to lower long-term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86-0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85-1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89-1.11) and in long-term mortality (RR 1.01, 95% CrI 0.91-1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long-term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations.

Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials.

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.

Respiratory Variation in Femoral Vein Diameter Has Moderate Accuracy as a Marker of Fluid Responsivity in Mechanically Ventilated Septic Shock Patients.

Ultrasound (US) is considered the first step in evaluation of patients with shock; respiratory variation of the inferior vena cava (inferior vena cava collapsibility [IVCc]) is an important measurement in this scenario that can be impaired by patient condition or technical skills. The main objective of this study was to evaluate if respiratory variation of the femoral vein (femoral vein collapsibility [FVc]), which is easier to visualize, can adequately predict fluid responsiveness in septic shock patients. Forty-five mechanically ventilated septic shock patients in a mixed clinical-surgical, 30-bed intensive care unit were enrolled in this study. All patients underwent assessments of FVc, IVCc and cardiac output using a portable US device. The passive leg raising test was used to evaluate fluid responsiveness. FVc presented an area under the receiver operating characteristic curve of 0.678 (95% confidence interval: 0.519-0.837, p = 0.044) with a cutoff point of 17%, yielding a sensitivity of 62% and specificity of 65% in predicting fluid responsiveness. IVCc had greater diagnostic accuracy compared with FVc, with an area under the receiver operating characteristic curve of 0.733 (95% confidence interval: 0.563-0.903, p = 0.024) and a cutoff point of 29%, yielding a sensitivity of 47% and specificity of 86%. In conclusion, FVc has moderate accuracy when employed as an indicator of fluid responsiveness in spontaneously mechanically ventilated septic shock patients.

Right ventricular tumor in a patient with melanoma.

Primary tumors of the heart are not common. However, metastatic neoplasms affecting the heart are more commonly found. Postmortem studies have shown that some tumors have reported secondary cardiac implants to be over 50%. Such involvement is to be taken into account for patients with a history of neoplasm and who present conduction disorders, murmur, cardiomegaly or arrhythmia. This is to report the case of a 39-year-old man who had been referred due to fatigue and dyspnea on effort. Echocardiogram evidence showed large tumoral mass in right ventricle. Medical history showed previous melanoma; further evaluation showed metastasis to lungs, heart and brain. Outcome was death. The uniqueness in this case relies on the large metastatic mass in right ventricle, thus illustrating a rare clinical condition of guarded prognosis.

Tumor em ventrículo direito em paciente com melanoma / Right ventricular tumor in a patient with melanoma

Os tumores primários cardíacos são infreqüentes; entretanto, as neoplasias metastáticas com acometimento do coração são mais comuns. Alguns tumores apresentam, em estudos post-mortem, implantes secundários cardíacos com freqüências que superam 50 por cento. Esse comprometimento deve ser lembrado em pacientes com história de neoplasia, que apresentem distúrbios de condução, sopro, cardiomegalia ou arritmias. Relatar-se-á, a seguir, o caso de um homem de 39 anos, encaminhado por cansaço e dispnéia aos esforços. Ecocardiograma evidenciou grande massa tumoral em ventrículo direito. A história médica pregressa revelou antecedentes de melanoma e a avaliação complementar mostrou doença metastática para pulmões, coração e cérebro, com evolução a óbito. Os aspectos singulares do caso são a presença de uma grande massa no ventrículo direito de origem metastática, ilustrando um quadro clínico raro e de prognóstico reservado.

Primary tumors of the heart are not common. However, metastatic neoplasms affecting the heart are more commonly found. Postmortem studies have shown that some tumors have reported secondary cardiac implants to be over 50 percent. Such involvement is to be taken into account for patients with a history of neoplasm and who present conduction disorders, murmur, cardiomegaly or arrhythmia. This is to report the case of a 39-year-old man who had been referred due to fatigue and dyspnea on effort. Echocardiogram evidence showed large tumoral mass in right ventricle. Medical history showed previous melanoma; further evaluation showed metastasis to lungs, heart and brain. Outcome was death. The uniqueness in this case relies on the large metastatic mass in right ventricle, thus illustrating a rare clinical condition of guarded prognosis.