Clinical trials that led to ibrutinib’s approval for the treatment of chronic lymphocytic leukemia showed that its side effects differ from those of traditional chemotherapy. Reasons for discontinuation in clinical practice have not been adequately studied. We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either commercially or on clinical trials. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. This multicenter, retrospective analysis included ibrutinib-treated chronic lymphocytic leukemia patients at nine United States cancer centers or from the Connect® Chronic Lymphocytic Leukemia Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. Six hundred sixteen ibrutinib-treated patients were identified. A total of 546 (88%) patients were treated with the commercial drug. Clinical trial patients were younger (mean age 58 versus 61 years, P=0.01) and had a similar time from diagnosis to treatment with ibrutinib (mean 85 versus 87 months, P=0.8). With a median follow-up of 17 months, an estimated 41% of patients discontinued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common reason for discontinuation in all settings. The median progression-free survival and overall survival for the entire cohort were 35 months and not reached (median follow-up 17 months), respectively. In the largest reported series on ibrutinib- treated chronic lymphocytic leukemia patients, we show that 41% of patients discontinued ibrutinib. Intolerance as opposed to chronic lymphocytic leukemia progression was the most common reason for discontinuation. Outcomes remain excellent and were not affected by line of therapy or whether patients were treated on clinical studies or commercially. These data strongly argue in favor of finding strategies to minimize ibrutinib intolerance so that efficacy can be further maximized. Future clinical trials should consider time-limited therapy approaches, particularly in patients achieving a complete response, in order to minimize ibrutinib exposure.

In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.

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The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies.

Steroid-refractory (SR) acute gastrointestinal (GI) graft-versus-host disease (GVHD) is associated with significant mortality in allogeneic hematopoietic cell transplantation recipients. We retrospectively evaluated the efficacy of tocilizumab for the treatment of SR biopsy-proven acute lower GI GVHD in 16 consecutive adult transplant recipients between October 2015 and July 2016. Tocilizumab 8 mg/kg was administered every 2 weeks until achievement of complete response, defined as resolution of all manifestations of GI GVHD, or until patients had progression or initiation of other therapy. Ten of 16 patients (62.5%; 95% CI, 0.39-82) achieved a complete response after a median time of 11 days (range, 2-28 days) from tocilizumab initiation. The median time to response onset (improvement in stage by at least 1) was 1 day (range, 1-4 days). Tocilizumab was administered at a median of 9 days (range, 3-75 days) from GVHD diagnosis and 10 days (range, 3-75 days) from initiation of high-dose steroids. At a median follow-up of 7.6 months (range, 0.8-27.7 months) from initiation of tocilizumab, 6/16 (37.5%) patients are alive and free of their underlying hematologic malignancy. Tocilizumab appears to be a highly active agent for the treatment of severe SR lower GI acute GVHD.

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.

Complementary and alternative medicine (CAM) is a diverse group of medical and health care systems, practices, and products that are not generally considered part of conventional medicine. Chronic lymphocytic leukemia (CLL) is the most common leukemia diagnosed in the western hemisphere, and 16.5% to 66% of patients have reported using CAM. Most patients use spiritual/mind-body techniques and high doses of vitamins and herbs (most commonly polyphenols, including teas). We have reviewed the reported data on green tea and turmeric use in CLL patients.

Introduction: Ibrutinib (Ibr) is a kinase inhibitor (KI) indicated for treating CLL. Clinical trials that led to its approval showed that its unique side effects differ from traditional chemotherapy toxicities. We previously reported (Mato et al, ASH 2015) that intolerance was the most common reason for discontinuation of Ibr in 123 patients treated in a real world setting. Whether reasons for discontinuation reported in clinical trials mirror those encountered in the real world is unknown and has not been studied. Therefore, we conducted a retrospective analysis of 621 CLL patients treated with Ibr either on clinical studies or commercially. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. Patients and Methods: This multicenter, retrospective analysis included Ibr-treated CLL patients at 9 US cancer centers or the Connect® CLL Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival (PFS) (time from KI treatment to progression, death or last f/u) as determined by the Kaplan Meier method. Comparisons of outcomes data were made using the log rank (LR) test. All other comparisons were descriptive. Results: 621 patients treated with Ibr were identified. Table 1 includes available baseline characteristics stratified by line of therapy. A total of 546 (88%) patients were treated with commercial drug. Clinical trial patients were younger (median age 57 vs. 61 years), had a longer time from diagnosis to Ibr (median 85 vs. 72 months) and were more consistently initiated at 420 mg daily (100% vs. 89%). With a median f/u of 14.5 months, the Ibr discontinuation rate was estimated to be 42% (median time to Ibr discontinuation was 7 months). Reasons for discontinuation are listed in table 2. Notably, Ibr toxicity was the most common reason for discontinuation in all settings. Ibr starting dose (420 mg daily vs. < 420 mg daily) did not impact the proportion of patients who discontinued Ibr due to toxicity (51% vs. 50%). In relapsed CLL, the 5 most common Ibr-related toxicities as a reason for discontinuation included: atrial fibrillation (12.3%), infection (10.7%), pneumonitis (9.9%), bleeding (9%), and diarrhea (6.6%). In front line CLL, the 3 most common Ibr-related toxicities as a reason for discontinuation included arthralgia (41.6%), atrial fibrillation (25%), and rash (16.7%). Median times to discontinuation by toxicity were as follows: bleeding (8 months), diarrhea (7.5 months), atrial fibrillation (7 months), infection (6 months), arthralgia (5 months), pneumonitis (4.5 months), and rash (3.5 months). Median PFS and OS for the entire cohort were 35 months and not reached (median f/u 17 months) respectively. Figure 1 describes PFS for Ibr treated patients stratified by line of therapy (A), reason for discontinuation (B), clinical trial participation (C) and depth of response (D). In a multivariable model, complex karyotype was validated as an independent predictor of PFS (HR 1.6, CI 1.1-2.5 p=.04) but not OS (HR 1.6, CI .9-3.1 p=.1). Conclusions: In the largest reported series on Ibr-treated CLL patients, we show that 40% of patients have discontinued Ibr during this observation period. Intolerance as opposed to CLL progression or transformation was the most common reason for discontinuation. As compared to previous reports from clinical trials, the discontinuation rate appears to be higher suggesting (1) a learning curve in terms of toxicity management, (2) a higher incidence of toxicity in clinical practice, (3) or a lower threshold for discontinuation given alternative choices. Outcomes remain excellent and were not impacted by line of therapy and whether patients were treated on studies or commercially. These data strongly argue to find strategies to minimize Ibr intolerance so that efficacy can be further maximized. Figure 1 Figure 1. Disclosures Mato: Abbvie, Acerta Pharma, Gilead Sciences, ProNAi, TG Therapeutics, Theradex: Research Funding; Abbvie, Gilead Sciences, Pharmacyclics, TG Therapeutics: Consultancy. Lamanna:Acerta: Research Funding; TGR Therapeutics: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria, Research Funding; Roche-Genentech: Honoraria, Research Funding; Celgene: Honoraria; AbbVie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Infinity: Research Funding; Acerta: Research Funding; TGR Therapeutics: Research Funding. Ujjani:Gilead: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy. Brander:TG Therapeutics: Research Funding; Gilead: Honoraria. Howlett:Sandoz: Honoraria; Teva: Speakers Bureau; Amgen: Honoraria; Pfizer: Honoraria; Eisai: Honoraria. Skarbnik:Gilead Sciences: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy. Cheson:Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kiselev:Celgene: Employment, Equity Ownership. Nasta:Millennium Pharmaceuticals: Research Funding. Schuster:Janssen Research & Development: Research Funding; Hoffman-LaRoche: Research Funding; Gilead: Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding. Porter:Novartis: Patents & Royalties, Research Funding; Genentech: Employment. Nabhan:Seattle Genetics: Research Funding; Cardinal Health: Consultancy; Infinity: Consultancy; Abbvie: Consultancy; Genentech: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; Astellas: Research Funding. Barr:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy.