ALBERT

Beschreibung: Introduction: Idelalisib (IDELA, Zydelig®) is the first-in-class PI3Kδ inhibitor and is approved in the U.S. as an oral monotherapy for relapsed / refractory follicular lymphoma (R/R FL) after at least two prior lines of systemic therapy. IDELA's regulatory approval was based on a phase 2, open-label clinical trial in 125 patients with R/R indolent non-Hodgkin's lymphoma (Gopal et al., NEJM, 2014) and outcomes in the FL subgroup were published by Salles et al. (Haematologica, 2017). The current study evaluates the characteristics and treatment patterns of patients treated with IDELA for R/R FL in a real-world setting. Methods: Adult patients diagnosed with R/R FL (grades 1, 2, and 3a) and treated with IDELA within the US Oncology Network (USON) between 7/1/2014 to 6/30/2018 were analyzed retrospectively. Patient data were obtained from USON's structured electronic health records' system, iKnowMed (iKM)TM. Manual chart review (ChR) was used to determine physician response and to confirm IDELA treatment patterns. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods. Descriptive statistics were generated for outcomes of interest, including duration of therapy (DoT), median follow-up, and adverse event (AE) frequency. Results: A total of 124 patients with FL and prescribed IDELA were identified in iKM TM. After Chr confirming the diagnosis of follicular lymphoma diagnosis and initiation of IDELA, 88 patients were retained for analysis. Median age of patients was 68.9 years, with 52.3% female and the majority white and non-Hispanic (90.9% and 93.2%, respectively, Table 1). The most common regimens immediately prior to IDELA initiation were bendamustine + rituximab (22.7%), rituximab (17%), and rituximab maintenance (11.4%). Eighty-six (97.7%) patients had co-morbidities categorized as vascular (50%), endocrine (33%), respiratory (13.6%), or cardiac (12.5%). Thirteen (14.8%), 21 (23.9%), and 54 (61.4%) patients initiated IDELA in second line (2L), 3L, and 〉4L, respectively. Baseline lab values at IDELA initiation were similar regardless of line of therapy (LOT). mDOT was 5.5 mos. for the entire population and was similar across all LOTs (4.1 mos., 6.1 mos., and 5.5 mos. in 2L, 3L, and 〉4L, respectively). AEs were noted in 45.5% with the most common being gastrointestinal (31.8%) and dermatologic (10.2%). Respiratory and infectious AEs were noted in 2.3% and 1.1%, respectively, although Pneumocystis jirovecii pneumonia (PJP) prophylaxis was rarely prescribed (2.3%). Toxicity as a reason for IDELA discontinuation varied in frequency across LOT and was more common in 2L compared to 3L and 〉4L (91.7% compared to 43.8% and 46.9%, respectively). With a median follow-up of 18.6 months for the population, the mPFS was 11.4 mos. [95%CI: 8.5,17.0] and mOS was 32.5 mos. [95% CI: 25.3,NR]. Stratified by LOT, median follow-up time, mOS, and mPFS were greater in 2L (30.8 mos., NR [95% CI: 27.37,NR], and 29.0 mos. [95% CI: 8.6,NR], respectively) than in 3L or 〉4L (3L: 17.9 mos., 29.4 mos. [95%CI: 18.6,NR], and 17.5 mos. [95% CI: 6.1,NR]; 〉4L: 16.5 mos., 25.3 mos. [95%CI: 13.5.,NR], and 8.6 mos. [95% CI: 6.1,12.6], respectively, Figures 1 and 2). Conclusion: Findings from this analysis suggest that R/R FL patients treated with IDELA in a real-world setting experience a similar mDOT and mPFS as those treated in the clinical trial setting (Salles et al., Haematologica, 2017). Patients treated in 2L demonstrated longer PFS and OS compared to later lines, but also experienced increased IDELA discontinuation due to toxicity, perhaps reflecting a lower incidence of progressive disease in earlier treatment lines, or a more immunocompetent population leading to higher rates of autoimmune AEs. Use of PJP prophylaxis in IDELA-treated patients was uncommon, an observation suggesting an opportunity for provider education. Our findings enhance available data on relapsed FL patient outcomes in real-world clinical practice and support the use of IDELA in patients with R/R FL after at least 2 systemic therapies. Disclosures Andorsky: Gilead: Research Funding; Genetech: Research Funding; CTI: Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding. Chan:Gilead Sciences, Inc.: Employment, Equity Ownership. Clark:McKesson: Consultancy, Employment, Equity Ownership. Ruzicka:Gilead Sciences, Inc.: Employment. Robert:McKesson: Employment. Awan:Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Gilead: Consultancy. OffLabel Disclosure: Idelalisib is a PI3 kinase inhibitor indicated for the treatment of patients with relapsed follicular B-cell lymphoma who have received at least two prior systemic therapies. Some patients in this observational study used Idelalisib after one prior systemic treatment.

Beschreibung: Introduction: Treatment patterns and clinical outcomes in elderly patients with DLBCL treated outside of clinical trials are poorly characterized. A previous report from Medicare Claims data found that 28% of patients above the age of 66 were treated with rituximab monotherapy or were not treated at all, with corresponding median survival of 18 and 2 months, respectively (Hamlin PA et al., Oncologist 2014; 19:1249-57). We conducted a retrospective chart review of diffuse large B cell lymphoma (DLBCL) patients diagnosed and managed within a community oncology practice network to evaluate treatment patterns and corresponding clinical outcomes. Methods: This was a retrospective observational chart review study of patients aged 60 years and over with newly diagnosed DLBCL. Eligibility criteria required a diagnosis between 1/1/2011 and 12/31/2012, with follow up through 12/31/14, plus no prior therapy for DLBCL. Data were obtained via programmatic query of the US Oncology Network/McKesson Specialty Health electronic health record database. Manual chart review was then performed on a subset of patients (n = 301) to confirm initial findings and gather additional information. Structured data elements were evaluated in univariate and multivariable logistic regression analysis in the subset of patients with stage 2 to 4 disease in order to determine factors associated with treatment with standard R-CHOP. Overall survival (OS) and progression free survival (PFS) were estimated from treatment initiation using the Kaplan Meier (KM) method. Results: 1151 patients who fit the eligibility criteria were identified. Age significantly influenced frontline treatment selection. Table 1 lists the percentage of patients with stage 2 to 4 disease treated with various regimens by age cohorts. "R-CHOP Alternative" was defined as one of the following: less than 6 cycles of R-CHOP, 〈 80% of full doses of agents in R-CHOP, or use of an alternative regimen like R-CVP, R-CEOP, or bendamustine-R. In multivariable analysis, age (OR=4.07 for age 65-79 and OR=7.98 for age 60-64; p

Beschreibung: Introduction Ibrutinib, a Bruton's tyrosine kinase inhibitor, was approved in the U.S. for the treatment of relapsed or refractory mantle cell lymphoma (MCL) in November of 2013. However, real-world data on ibrutinib use for the treatment of MCL is limited. The purpose of this study was to examine ibrutinib use, dosages, and reasons for treatment discontinuation among MCL patients treated in a community oncology practice setting. Methods The study population consisted of adult (≥18 year old) MCL patients treated with ibrutinib between November 1, 2013 and October 31, 2016, who were not enrolled in a clinical trial and had at least 2 visits to a US Oncology Network (USON) clinic. Patients with other primary cancers were excluded. Patient data were sourced from the USON's electronic health records system, iKnowMed (iKM)™. The structured iKM database provided information on demographics and clinical and treatment characteristics. Manual chart review was used to confirm ibrutinib treatment patterns. Duration of ibrutinib therapy (DOT), overall survival (OS), and progression-free survival (PFS) from systemic treatment initiation were estimated using Kaplan-Meier methods. Events were defined as death in the OS analysis, and progression or death in the PFS analysis. Patients were censored if their treatment was ongoing for DOT. Censors for OS and PFS were patients lost to follow up or those who did not experience a failure event within the study period. Results 159 eligible MCL patients were identified through iKM. The majority of patients were Caucasian (n=141, 88.7%), male (n=121, 76.1%), and diagnosed with Stage IV disease (n=117, 73.6%). Median follow-up for the population was 16.1 months. Approximately 7.5% (n=12) of patients received ibrutinib as first-line therapy (1L), compared to 54.1% (n=86) in 2L and 38.4% (n=61) in 3L or beyond. Median ibrutinib dose at initiation was 560mg (range: 140-700). During ibrutinib treatment, 16.4% (n=26) of patients experienced a dose reduction. Dose holds occurred in 30.2% (n=48), 66.7% (n=32) due toxicities. The overall discontinuation rate was 83.6% The primary reason for discontinuation was disease progression (n=46, 34.6%) followed by toxicities (n=34, 25.6%). Median DOT was higher for patients initiating treatment in 3L+ (14.9: 95% CI 8.8-17.1) compared to other lines. Median PFS was 19.6 (95% CI: 16.5-24.3) for the overall population and median OS was 25.8 months (95% CI: 19.9-not reached). Conclusions Our real-world findings on survival are consistent with those from clinical trials on ibrutinib in relapsed/refractory MCL, although our observed discontinuation rate (~84%) was higher than that of the trial (~58%), which had a similar median follow-up time (16.1 months vs. 15.3 months, respectively). Our findings provide additional data on MCL treatment patterns and patient outcomes in clinical practice. Disclosures Sharman: Acerta: Consultancy, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding. Kabadi:AstraZeneca: Employment. Clark:McKesson Specialty Health: Employment, Equity Ownership. Amirian:McKesson Specialty Health: Employment. Andorsky:Celgene: Research Funding; CTI BioPharma: Consultancy, Research Funding; AstraZeneca: Consultancy; Genentech: Consultancy.

Beschreibung: Introduction: The 2017 US FDA approval of a subcutaneous (SC) injection form of rituximab made available an alternative means of administering rituximab for patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). Although patients have reported a preference for SC rituximab injection (R-SC) over intravenous rituximab infusion (R-IV), nurse provider preferences for R-SC versus R-IV in the real-world setting have not been studied. Here, we report the findings of a survey designed to assess nurse treatment preferences for R-SC versus R-IV. Methods: A descriptive, cross-sectional survey of 208 oncology nurse providers was conducted via a web-based questionnaire between June 6, 2019 and July 10, 2019. Nurses who administered at least one R-IV and at least one R-SC treatment between July 1, 2017 and April 30, 2019 in US Oncology Network (USON) clinics were eligible to participate. The survey comprised 21 items, and evaluated nurses' experience with R-SC versus R-IV, preference for SC or IV administration, convenience, and overall experience. Results: Of the 208 nurse providers invited to participate in the survey, 43 completed the survey (20.7% response rate). Almost all nurses who completed the survey were familiar with administering R-IV, with 70% of the respondents administering 〉20 infusions in the past year. Nurses were also familiar with administering R-SC, with 56% of respondents administering 1-10 injections in the past year and 44% administering 〉10 injections in the past year. Fifty-three percent of respondents preferred administering R-SC over R-IV, with time saving, convenience, and patient preference chosen as the most common reasons. Most respondents (58%) had a positive/very positive experience with R-SC over R-IV, as a result of patient time saved, clinic/staff time saved, and quality time with patients. In total, 19% of respondents had a neutral experience with R-SC compared with R-IV. Of those reporting a neutral experience with R-SC, a comparable ease of administration was the most common reason. Twenty-three percent of respondents reported a negative/very negative experience with R-SC, with discomfort with the R-SC route of administration (i.e. physical effort) chosen as the most common reason for the negative experience. Eighty-four percent of respondents reported spending 1.5 to over 2 hours of nursing time monitoring and administering R-IV for each patient. The majority of respondents (98%) agreed that chair time could be saved with each administration of R-SC compared with R-IV. Respondents reported that the time saved could be used to see more patients (50%), complete nursing procedures (36%), and complete administrative work (14%). Forty-four percent of respondents reported that 1.5 to 2 hours could be saved with each administration of R-SC as compared with R-IV, with 67% of respondents agreeing that the quality of patient care was not impacted by the shorter administration time of R-SC. In terms of convenience, 63% of respondents reported R-SC is more convenient than R-IV, and 49% reported their overall impression of injecting R-SC as easy. Moreover, 49% reported that they agreed or strongly agreed that they would recommend R-SC to their medical colleagues, and 63% agreed or strongly agreed that they believe patients would prefer R-SC over R-IV. Conclusions: Based on an online survey of nurse providers with experience administering R-IV and R-SC, a majority of nurse providers preferred administering R-SC over R-IV. Time saved, convenience, and patient preference contributed to the positive experience with R-SC. Acknowledgements: This study was sponsored by Genentech, Inc. Third party editorial assistance, under the direction of Mitul Gandhi and Sheila Shapouri, was provided by Katie Buxton of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche Ltd. Disclosures Gandhi: Seattle Genetics: Other: Education ; Pharmacyclics: Other: Food and beverage ; AbbVie: Other: Food and beverage ; Pfizer: Other: Education ; GSK: Other: Food and beverage ; Genentech, Inc.: Other: Food and beverage ; Acerta Pharma: Research Funding. Shapouri:Genentech, Inc.: Employment; Roche: Equity Ownership. Ravelo:Genentech: Employment, Equity Ownership. Sudharshan:McKesson: Consultancy, Employment. Clark:McKesson: Consultancy, Employment, Equity Ownership. Dawson:Genentech: Employment; Roche/Genentech: Equity Ownership.

Beschreibung: Introduction:Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the unregulated proliferation of myeloid cells in the bone marrow and their accumulation in the blood. The approval of imatinib (IM) and second-generation TKIs have substantially improved survival for patients with CML. Despite the effectiveness of these TKIs in controlling CML, continuous therapy is necessary for most patients, and may be associated with the development of unfavorable adverse events such as hepatotoxicity. Although patients with elevated liver function tests are excluded from key clinical trials, case reports and small single-center studies have described cases of TKI-associated hepatotoxicity among patients with CML. This study sought to describe the prevalence and incidence of hepatotoxicity in patients with newly diagnosed Philadelphia chromosome-positive chronic-phase (Ph+ CP) CML treated with 1L TKIs in community oncology practices. Methods:This retrospective, observational cohort study identified adult patients newly diagnosed with Ph+ CP CML and treated with 1L dasatinib (DAS), IM, or nilotinib (NIL) within the US Oncology Network (USON) between 1 January 2008 and 30 November 2018. Patients were required to have at least one comprehensive metabolic panel (CMP) within 90 days of treatment start, and ≥ 1 CMP during follow-up. Additionally, patients had to have at least two visits within the USON, no enrollment in any clinical trial during the study period, and no documentation of other primary cancer diagnoses. Descriptive statistics were generated for baseline patient characteristics and prevalence and incidence of hepatotoxicity, and were stratified by 1L TKI treatment initiation. Grades for hepatotoxicity were derived from laboratory data using the Common Terminology Criteria for Adverse Events version 5. Results:A total of 2743 patients with CP-CML were identified. Of those, 730 (26.6%), 1455 (53.0%), and 558 (20.3%) patients were treated with 1L DAS, IM, or NIL, respectively. With the exception of age and region, patient demographic characteristics were well balanced across cohorts. However, baseline hepatic functioning differed across TKIs (Table 1). Prevalence of any-grade liver enzyme elevation was observed in almost one-third (31.9%) of patients, including 246 (33.7%) patients treated with DAS, 416 (28.6%) patients treated with IM, and 213 (38.2%) patients treated with NIL. Among all patients with normal baseline hepatic function, 48.9% developed any-grade hepatotoxicity while on 1L therapy. Across TKI cohorts, significantly more patients treated with NIL developed any-grade hepatotoxicity (70.1%) compared to patients treated with DAS (45.5%) or IM (43.5%) (P〈 0.0001). Among all patients receiving 1L treatment, 1.5% to 3.8% of patients experienced grade 3-4 hepatotoxicity. Significant differences in the proportion of patients that developed grade 3-4 hepatotoxicity were observed across treatments and were most common among patients treated with NIL (Table 2). Conclusions:Findings from this analysis suggest that hepatic dysfunction may be common at baseline among patients with CP-CML treated in real-world community oncology settings. Among patients with normal baseline hepatic function, more patients treated with NIL experienced any-grade hepatotoxicity. Patients treated with NIL were also more likely to develop grade 3-4 hepatotoxicity compared to patients treated with DAS or IM. These findings may provide insight into the effects of long-term TKI treatment on hepatic functioning and help to inform treatment choices for patients. Disclosures Kolibaba: AbbVie:Research Funding;Compass Oncology:Ended employment in the past 24 months;Janssen:Research Funding;TG Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;McKesson Life Sciences:Consultancy;Sumitomo Dainippon Pharma Oncology:Consultancy, Other: travel, accommodations, expenses, ;Gilead:Research Funding;Genentech:Research Funding;Cell Therapeutics:Research Funding;Celgene:Research Funding;Acerta:Research Funding;Atara Biotech:Membership on an entity's Board of Directors or advisory committees;Verastem:Honoraria;Seattle Genetics:Research Funding;Novartis:Research Funding;Pharmacyclics:Research Funding.Zhou:McKesson Corporation:Current Employment.Keating:Bristol Myers Squibb:Current Employment.Clark:McKesson Life Sciences:Current Employment, Current equity holder in publicly-traded company.Brokars:Bristol Myers Squibb:Current Employment.Kee:Bristol Myers Squibb:Current Employment.Copher:Bristol Myers Squibb:Current Employment.Stwalley:Bristol Myers Squibb:Current Employment, Current equity holder in publicly-traded company.Jabbour:Adaptive Biotechnologies:Other: Advisory role, Research Funding;Genentech:Other: Advisory role, Research Funding;BMS:Other: Advisory role, Research Funding;Amgen:Other: Advisory role, Research Funding;Pfizer:Other: Advisory role, Research Funding;Takeda:Other: Advisory role, Research Funding;AbbVie:Other: Advisory role, Research Funding.

Beschreibung: Introduction: Current National Comprehensive Cancer Network (NCCN) guidelines recommend one of three frontline (1L) regimens to treat stage III or IV classical Hodgkin Lymphoma (cHL): doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD), or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated (e) dose-BEACOPP). PET/CT imaging is important at initial staging and in follow up including after two cycles (interim PET2) to assess and adapt treatment based on response for patients who newly start treatment with ABVD (Johnson et al., 2016). Despite NCCN guidelines, physicians in community oncology practices may face challenges optimizing outcomes for ABVD patients utilizing the interim PET2 adaptive approach. This study evaluated interim PET2 utilization and reported Deauville scores (DS) in patients with stage III or IV cHL treated in the 1L setting. Methods: This retrospective observational study included adult patients diagnosed with stage III or IV cHL and treated with 1L ABVD, A+AVD, or eBEACOPP within the US Oncology Network (USON) between 01 January 2017 and 31 January 2020. Patients enrolled in therapeutic clinical trials or received treatment for another primary cancer diagnosis were excluded. Patient data were sourced from the USON's electronic health records database, iKM™. Demographic, clinical, and treatment characteristics were sourced from structured iKM elements. Interim PET2 details, including Deauville scores, were obtained from manual chart review. Descriptive statistics were generated for all patient characteristics. Results: 262 patients with cHL were eligible. The majority of the patients were