Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial.

IMPORTANCE: Recently, the benefit of adding daratumumab to the proteasome inhibitor-based, 3-drug combination of bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who underwent high-dose melphalan chemotherapy and autologous hemopoietic cell transplant was assessed. Here, we examine the addition of daratumumab to the second-generation proteasome inhibitor-based, 3-drug combination of carfilzomib, lenalidomide, and dexamethasone. OBJECTIVE: To assess the safety and effectiveness of carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy for patients with newly diagnosed multiple myeloma, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant. DESIGN, SETTING, AND PARTICIPANTS: Clinical and correlative pilot study at the Memorial Sloan Kettering Cancer Center in New York, New York. Patients with newly diagnosed multiple myeloma were enrolled between October 1, 2018, and November 15, 2019. The median follow-up from start of treatment was 20.3 months (95% CI, 19.2-21.9 months). INTERVENTIONS: Eight 28-day cycles with intravenous carfilzomib, 20/56 mg/m2 (days 1, 8, and 15); oral lenalidomide, 25 mg, (days 1-21); dexamethasone, 40 mg weekly, orally or intravenously (cycles 1-4), and 20 mg after cycle 4; and intravenous daratumumab, 16 mg/kg (days 1, 8, 15, and 22 [cycles 1-2]; days 1 and 15 [cycles 3-6]; and day 1 [cycles 7 and 8]). MAIN OUTCOMES AND MEASURES: The primary end point was the minimal residual disease (MRD) rate, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant. Secondary end points included determining safety and tolerability, evaluating rates of clinical response per the International Myeloma Working Group, and estimating progression-free survival (PFS) and overall survival (OS) rates. RESULTS: Forty-one evaluable patients were enrolled (median age, 59 years; range, 30-70 years); 25 (61%) were female, and 20 (49%) had high-risk multiple myeloma. The primary end point (MRD negativity in the bone marrow; 10-5 sensitivity) was achieved in 29 of 41 patients (71%; 95% CI, 54%-83%), and therefore the trial was deemed successful. Median time to MRD negativity was 6 cycles (range, 1-8 cycles). Secondary end points of the overall response rate and the very good partial response or complete response rate were 100% (41 of 41 patients) and 95% (39 of 41 patients), respectively. At 11 months of the median follow-up, the 1-year PFS rate and the OS rate were 98% (95% CI, 93%-100%) and 100%, respectively. Most common (≥2 patients) grade 3 or 4 adverse events were neutropenia (12 patients [27%]), rash (4 patients [9%]), lung infection (3 patients [7%]), and increased alanine aminotransferase level (2 patients [4%]). There were no deaths. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy was associated with high rates of MRD negativity in patients with newly diagnosed multiple myeloma and high rates of PFS.

Immunoglobulin Light-Chain Amyloidosis: Clinical Presentations and Diagnostic Approach.

Systemic immunoglobulin light-chain (AL) amyloidosis is a rare disorder arising from a plasma cell clone that produces misfolded immunoglobulin light chains, which are deposited in various tissues and organs as amyloid fibrils. Signs and symptoms are typically vague and overlap with those arising from other common diseases; consequently, diagnosis of AL amyloidosis is challenging for clinicians. Substantial delays between onset of symptoms and diagnosis are common, and result in poorer outcomes, particularly in patients with cardiac AL amyloidosis and others who develop advanced organ dysfunction. With the need to identify AL amyloidosis as early as possible, it is important for health-care practitioners, including advanced practice clinicians and nurses, to be aware of the hallmark presenting signs and symptoms, as well as the latest practice for evaluation and diagnosis. Increased awareness of signs and symptoms associated with AL amyloidosis, particularly relating to the most frequently involved organs, the heart and kidneys, represents an opportunity for achieving earlier diagnosis. Here we review these issues in AL amyloidosis, summarize the key presenting symptoms that clinicians need to be alert to, and discuss the latest diagnostic tests, with the aim of expediting patient identification and diagnosis with the goal of improving patient outcomes.

Removal capacity and chemical speciation of groundwater iodide (I-) and iodate (IO3-) sequestered by organoclays and granular activated carbon.

Radioiodine (present mostly as 129I) is difficult to remove from waste streams or contaminated groundwater because it tends to exist as multiple anionic species (i.e., iodide (I-), iodate (IO3-) and organo-iodide) that do not bind to minerals or synthetic materials. In this work, the efficacy of organoclay OCB and OCM, and granular activated carbon (GAC) as sorbents to bind I- and IO3- from artificial groundwater (AGW) was examined. These sorbents were highly effective at removing I- and IO3- from AGW under oxic condition, with the adsorption capacity up to 30 mg I/g sorbent. Based on X-ray spectroscopy measurements, I- was bound to organic ligands in organoclays OCB and OCM, but when GAC was exposed to I- in groundwater, the sequestered I species was molecular I2. For IO3- interacting with organoclay OCB and GAC, the adsorbed I species remained being IO3-, but when organoclay OCM that contains both quaternary amine and sulfur was exposed to IO3-, the sulfur compound would reduce IO3- to I- that was then bound to organic ligands. Thus, the inexpensive and high-capacity organoclays and GAC may provide a practical solution for removing 129I contaminant from environmental systems and liquid nuclear wastes.