Introduction: Rasburicase, a recombinant form of urate oxidase, is a highly effective treatment for tumor lysis syndrome (TLS). Although the FDA-approved dose for rasburicase is 0.2 mg/kg/day for up to five days, many centers have adopted alternative dosing strategies to decrease cost, the most common being a single 6 mg dose. We hypothesized that further reducing the dose to 3 mg would result in similar efficacy and yield significant cost savings compared to the 6 mg dose strategy. Methods: We conducted a retrospective cohort study to examine the comparative effectiveness of a single 3 mg dose of rasburicase versus a single 6 mg dose in 108 adults with hematological malignancies presenting with a baseline uric acid (UA) ≤ 12 mg/dL between June 2009 and February 2015. Prior to January 2012, our institutional policy recommended a single 6 mg dose for all patients who met criteria for rasburicase for TLS. In January 2012, the policy was amended to recommend a single 3 mg dose for patients with a baseline UA ≤ 12 mg/dL. Thus, the study included 56 patients with UA ≤ 12 who received a single 6 mg dose prior to the policy modification and 52 patients with UA ≤ 12 given the 3 mg dose after the amendment. The primary endpoint was the percentage of patients who achieved a UA ≤ 8 mg/dL (the upper limit of normal at our institution) 24 hours after a single dose of rasburicase. Fisher's exact test was used to analyze categorical variables and t-tests were used to analyze continuous variables. The a priori level of significance was set at α < 0.05. Results: The mean baseline UA was 9.3 mg/dL and 9.8 mg/dL in the 3 mg arm and 6 mg arm, respectively (P = .19). At 24 hours there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL (92% vs. 98%; P = 0.36). In addition, there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL at 48 hours (98% vs. 100%; P = 0.48). Six (11.5%) patients in the 3 mg arm and one (1.8%) patient in the 6 mg arm required a second dose of rasburicase to achieve a UA <8 mg/dL (P = 0.1). Of note, the 6 mg group had a greater percent reduction in UA from baseline compared to the 3 mg group at both 24 hours (-68.1% vs. -48.6%; P < .01) and 48 hours (-69.3% vs. -51.3%; P = 0.02) after rasburicase administration. There was no difference in the percent change of serum creatinine between the two dosing strategies at 24 hours (-6.5% vs. 0.1%; P = 0.11) or 48 hours (-4.5% vs. -2.5%; P = 0.22). In addition, no difference was observed with respect to the percent of patients who required renal replacement therapy within 7 days of rasburicase administration (8.9% vs. 9.6% P = 1.0). Based on the average wholesale price of $815 for one 1.5 mg vial of rasburicase, the single 3 mg dose was associated with approximately $1,500 cost savings per encounter compared to the 6 mg dose. Conclusion: A single 3 mg dose of rasburicase was as effective as 6 mg in normalizing UA within 24 hours. Our findings demonstrate that administering a single 3 mg dose of rasburicase is a cost-effective alternative for TLS management in patients with hematological malignancies presenting with a UA ≤ 12 mg/dL. Disclosures Svoboda: Immunomedics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding. Ganetsky:Onyx: Speakers Bureau.
Introduction: Severe steroid-refractory (SR) gastrointestinal acute graft-versus-host disease (GI-GVHD) is associated with significant mortality in allogeneic hematopoietic cell transplantation (HCT) recipients. Although numerous agents have been studied for this indication, long-term outcomes remain dismal. Tocilizumab, an interleukin-6 receptor monoclonal antibody, is active in SR GI-GVHD with varying efficacy and impact on survival. Tocilizumab was recently adopted at our center as initial therapy for SR GI-GVHD. Methods: We retrospectively evaluated the efficacy of tocilizumab for the treatment of SR biopsy-proven GI-GVHD in 5 consecutive adult allogeneic HCT recipients between October 2015 and July 2016. All patients had stage IV GI GVHD (Glucksberg criteria) without other organ involvement at time of tocilizumab initiation. Three patients underwent myeloablative conditioning and two reduced-intensity conditioning for a hematologic malignancy (AML n=3; ALL n=1; myelofibrosis n=1). SR GI-GVHD was defined as progressive symptoms after 3 days or no improvement after 7 days of methylprednisolone 2 mg/kg/day. Tocilizumab 8 mg/kg was administered approximately every 2 weeks until achievement of complete response (CR), defined as resolution of all manifestations of GI GVHD, progression or initiation of other therapy. Serum levels of pro-inflammatory cytokines (IFN-γ, IL-2, IL-2R, IL-6, IL-7, IL-15, TNF-α) were measured prior to and after the start of tocilizumab using multiplex arrays. Results: All 5 patients (100%; 95% CI, 0.52 - 1.00) achieved a CR after a median time of 9 days (range, 8 - 13) from tocilizumab initiation. The median time to response onset (improvement in GVHD stage by at least 1) was 1 day (range, 1 - 2). Tocilizumab was administered at a median of 17 days (range 8 - 25) from GVHD diagnosis and 15 days (range, 7 - 18) from initiation of high-dose steroids. The median number of tocilizumab doses administered was 2 (range, 1 - 4). Two patients achieved CR after a single dose and 3 patients required multiple doses of tocilizumab to achieve CR (2 doses n=1; 3 doses n=1; 4 doses n=1). At a median follow up of 5.6 months (range, 2.1 - 8.5) from initiation of tocilizumab, 3 of 5 patients are alive and free of their underlying hematologic malignancy. One patient died from complications related to biopsy-proven liver GVHD that developed after tocilizumab initiation and 1 patient died from polymicrobial sepsis. Serum levels of IL-6 prior to the start of tocilizumab ranged from 4 - 21 pg/mL (normal 0 - 12). As all patients responded, no associations between serum levels of pro-inflammatory cytokines, including IL-6, and tocilizumab response could be identified. Conclusion: Tocilizumab appears to be a highly active agent for the treatment of SR GI-GVHD. Detailed evaluation through prospective clinical trials is warranted. Disclosures Frey: Servier: Consultancy; Amgen: Consultancy; Novartis: Research Funding. Mangan:Incyte: Other: Advisory Board; Novartis: Research Funding. Gill:Novartis: Patents & Royalties, Research Funding. Cohen:Bristol-Meyers Squibb: Consultancy, Research Funding; Janssen: Consultancy. Porter:Novartis: Patents & Royalties, Research Funding; Genentech: Other: Spouse Employment.
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