Adeela Mushtaq

Emerging immune targets for the treatment of multiple myeloma

We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab. We included seven clinical trials on chimeric antigen receptor (CAR) T cells. CAR T-cell targets include BCMA, CD19, KLC and CD138. A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising.

Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (nu202f=u202f5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70u202fmg/m2 dose of CFZ vs standard 20-27u202fmg/m2 dose in NDMM and RRMM.

Intractable cerebral Nocardia mexicana in a GvHD patient successfully treated with linezolid

Intractable cerebral Nocardia mexicana in a GvHD patient successfully treated with linezolid

A 20-year experience with nocardiosis in solid organ transplant (SOT) recipients in the Southwestern United States: A single-center study

Nocardiosis is a life‐threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%‐3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors.

1075: SPONTANEOUS TENSION HEMOTHORAX

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Rapid accumulation of blood in the pleural cavity causing tension physiology with mediastinal shift, cardiac compression and obstructive shock has been described only in the presence of aortic or great vessel rupture, trauma or rib fracture. Spontaneous occurrence of this phenomena has not been previously described. Methods: A 61 y-o woman with history of myelodysplastic syndrome (MDS) presented with sudden onset of acute dyspnea. She was severely hypotensive and showed clinical signs of profound circulatory shock. During her initial resuscitation and evaluation, chest radiograph showed complete opacification of the left hemithorax with marked shift of the trachea and mediastinum to the left. Point of care ultrasonography for shock showed presence of pleural fluid on the left causing compression of the cardiac chambers in multiple planes of view. Tube thoracostomy was done with a 32 Fr. chest tube and 1.8 liters of blood was evacuated. Immediate relief of symptoms and restoration of blood pressure was noted. The patient had severe thrombocytopenia (platelets < 20,000/ cu.mm) due to MDS. There was no history of recent or remote trauma, excessive or forceful coughing or recent chest or neck procedures. Extensive workup including CT angiography and echocardiography also did not reveal any traumatic or mechanical source of the hemorrhage. Correction of platelet count and supportive care was provided. There was no re-accumulation of blood. Results: Spontaneous bleeding in patients with MDS, bone marrow malignancies and thrombocytopenia can occur when the platelet count drops below 30,000/cu.mm. While intracranial, gastrointestinal and retroperitoneal hemorrhage have been reported, spontaneous hemorrhage into the pleural cavity is rare. Tension hemothorax due to spontaneous pleural cavilty hemorrhage has not been previously presented. Our case demonstrates that rapidly accumulation of viscous fluid in the pleural cavity can cause obstructive shock and respiratory failure similar to tension pneumothorax. Bedside critical care ultrasonography for shock evaluation that showed cardiac compression by extracardiac and extra-pericardial fluid, was essential to ascertain that the patient’s shock was caused by pleural fluid. Cardiac compression and impairment of bi-ventricular outflow helped distinguish the tension physiology from that of a chronic pleural effusion. Our case illustrates the recognition of this rare clinical entity as well as its early identification by ultrasonography.

Prophylaxis for Hepatitis B Virus Reactivation after Allogeneic Stem Cell Transplantation in the Era of Drug Resistance and Newer Antivirals: A Systematic Review and Meta-Analysis

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.