Association of adverse events and associated cost with efficacy for approved relapsed and/or refractory multiple myeloma regimens: A Bayesian network meta-analysis of phase 3 randomized controlled trials.

BACKGROUND: Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs). METHODS: Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs). RESULTS: Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). CONCLUSIONS: The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM.

Trends in the use of therapeutic plasma exchange in multiple myeloma.

INTRODUCTION: Therapeutic plasma exchange (TPE) is traditionally performed for hyperviscosity, neuropathy and to mitigate renal injury in the setting of high clonal free light chain burden in patients with multiple myeloma (MM) with unknown clinical benefit. MATERIALS AND METHODS: Retrospective study of adults ≥18 years with MM who received TPE in the in-patient setting in the United States from 1993 to 2015. We examined the temporal trends of TPE utilization in MM hospitalizations, hospital charges, in-hospital mortality, and length of hospitalization and the predictors of in-hospital mortality and length of hospitalizations. RESULTS: The number of MM-hospitalizations for TPE in adults increased significantly from 1993 to 2015 (1% in 1993-1999 to 2.1% in 2008-2015 of all MM discharges, P for trend <.0001). About 70% of TPE recipients had acute kidney injury (AKI). The median hospital charges increased 5-fold during the time period ($ 24 407 to $ 113 496; P for trend <.0001). In-hospital mortality decreased (17.5% (SE 2.66) in 1993-1997 to 8.7% (1.39) in 2007 to 2013) P for trend <.005) while the length of stay remained unchanged (11.2 days vs 11.9 days, P for trend 0.17). On adjusted analysis, significant predictors of in-hospital mortality among MM TPE recipients include, Charlson Comorbidity Index (CCI) (3 vs 2 adjusted odds ratio, aOR 2.16, 95% CI 1.26-3.71; P = .005), year (continuous) (aOR 0.93, 95% CI 0.90-0.96; P < .001) and race (other vs white; aOR 0.44, 95% CI 0.25-0.78; P = 0.004). CONCLUSIONS: There has been a substantial increase in the use and associated cost of TPE in hospitalized MM patients.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis syndrome and collapsing focal segmental glomerulosclerosis.

Collapsing glomerulopathy is a distinct and aggressive clinicopathologic variant of focal segmental glomerulosclerosis (FSGS). Here we present a 46-year-old man with acute renal failure from biopsy-proven collapsing FSGS and nephrotic syndrome in the setting of a diagnosis of hemophagocytic lymphohistiocytosis secondary to acute Epstein-Barr virus infection. This rare association has not been well described previously.

Baclofen-induced toxicity in renal disease with neurotoxicity and skin rash.

Baclofen is approved by the Food and Drug Administration for spasticity and is also used off-label for trigeminal neuralgia, cluster headache, and substance abuse dependency. Baclofen is 90% renally excreted and has a variable threshold for toxicity in patients with chronic kidney disease. We present a case of accidental overdose of baclofen in a 58-year-old woman with intractable trigeminal neuralgia. She presented with baclofen neurotoxicity symptoms including confusion and tremors and had a morbilliform rash in the dorsum of both hands. This simultaneous presentation is rare and has never been reported. Her symptoms resolved after hemodialysis treatment.

Hydrocodone snorting leading to hypersensitivity pneumonitis.

We present a case of hypersensitivity pneumonitis caused by intranasal abuse of the prescription narcotic hydrocodone. The patient's clinical course was complicated by acute respiratory failure. A chest radiograph showed diffuse bilateral opacities. The patient was treated with noninvasive ventilation, a high dose of intravenous steroids, and bronchodilators, resulting in improvement of symptoms and radiographic appearance.