Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 3-year follow-up of a multicenter, retrospective clinical experience with 319 cases outside of controlled clinical trials.

The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups.

Extracorporeal membrane oxygenation for adult respiratory distress syndrome in trauma patients: A case series and systematic literature review.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (vv-ECMO) is an established salvage therapy for severe respiratory failure, and may provide an alternative form of treatment for trauma-induced adult respiratory distress syndrome (ARDS) when conventional treatments have failed. The need for systemic anticoagulation is a relative contraindication for patients with bleeding risks, especially in multitraumatic injury. METHODS: We describe a case series of four trauma patients with ARDS who were managed with ECMO admitted to the neuro critical care unit at Addenbrooke's Hospital, Cambridge (UK), from January 2000 to January 2016. We performed a systematic review of the available literature to investigate the safety and efficacy of vv-ECMO in posttraumatic ARDS, focusing on the use of different anticoagulation strategies and risk of bleeding on patients with multiple injuries. RESULTS: Thirty-one patients were included. A heparin bolus was given in 16 cases. Eleven patients developed complications during treatment with ECMO with three cases of major bleeding. In all documented cases of bleeding a bolus and infusion of heparin was administered, aiming for an activated clotting time (ACT) target longer than 150 seconds. Two patients treated with heparin-free ECMO developed thromboembolic complications. Four patients died, and death was never directly or indirectly related to use of ECMO. CONCLUSION: vv-ECMO can be lifesaving in respiratory failure. Our experience and our literature review suggest that vv-ECMO should be considered as a rescue treatment for the management of severe hypoxemic respiratory failure secondary to ARDS in trauma patients.For patients with a high risk of bleeding, the use of ECMO with no initial anticoagulation could be considered a valid option. For patients with a moderate risk of bleeding, use of a heparin infusion keeping an ACT target shorter than 150 seconds can be appropriate. LEVEL OF EVIDENCE: Therapeutic study, level V.

Intracranial pressure after subarachnoid hemorrhage.

OBJECTIVES: To describe mean intracranial pressure after aneurysmal subarachnoid hemorrhage, to identify clinical factors associated with increased mean intracranial pressure, and to explore the relationship between mean intracranial pressure and outcome. DESIGN: Analysis of a prospectively collected observational database. SETTING: Neuroscience ICU of an academic hospital. PATIENTS: One hundred sixteen patients with subarachnoid hemorrhage and intracranial pressure monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Episodes of intracranial pressure greater than 20 mm Hg lasting at least 5 minutes and the mean intracranial pressure for every 12-hour interval were analyzed. The highest mean intracranial pressure was analyzed in relation to demographic characteristics, acute neurologic status, initial radiological findings, aneurysm treatment, clinical vasospasm, and ischemic lesion. Mortality and 6-month outcome (evaluated using a dichotomized Glasgow Outcome Scale) were also introduced in multivariable logistic models. Eighty-one percent of patients had at least one episode of high intracranial pressure and 36% had a highest mean intracranial pressure more than 20 mm Hg. The number of patients with high intracranial pressure peaked 3 days after subarachnoid hemorrhage and declined after day 7. Highest mean intracranial pressure greater than 20 mm Hg was significantly associated with initial neurologic status, aneurysmal rebleeding, amount of blood on CT scan, and ischemic lesion within 72 hours from subarachnoid hemorrhage. Patients with highest mean intracranial pressure greater than 20 mm Hg had significantly higher mortality. When death, vegetative state, and severe disability at 6 months were pooled, however, intracranial pressure was not an independent predictor of unfavorable outcome. CONCLUSIONS: High intracranial pressure is a common complication in the first week after subarachnoid hemorrhage in severe cases admitted to ICU. Mean intracranial pressure is associated with the severity of early brain injury and with mortality.

Biological activity of lenalidomide and its underlying therapeutic effects in multiple myeloma.

Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs) and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host's immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN) as a possible mediator of its therapeutical effects.