Impact of bodyweight (BW)-based starting doses on safety and efficacy of lenvatinib (LEN) in patients (pts) with hepatocellular carcinoma (HCC).

e16119 Background: In Study 202, pts received LEN 12 mg/d for treatment of unresectable (u)HCC, irrespective of BW. Correlations between early dose adjustments and BW in Study 202 led to BW-adjusted dosing in the phase 3 REFLECT study of LEN in uHCC. In REFLECT, pts <60 kg received LEN 8 mg/d and pts ≥60 kg received LEN 12 mg/d. While improvements in safety were expected by reducing the LEN starting dose to 8 mg/d in pts <60 kg, any differences in safety and efficacy of BW-adjusted dosing vs standard dosing among pts with lower BW have yet to be determined. Herein, we compare safety and efficacy of LEN based on pts’ BW (<60 kg vs ≥60 kg) in Study 202 (LEN 12 mg/d irrespective of BW) and in Japanese pts in REFLECT (dose adjusted by BW). Methods: This ad hoc analysis included all pts from Study 202 (n=46; all Asian, 43 Japanese) and Japanese pts from REFLECT (n=81). Safety and efficacy were assessed in Study 202 and REFLECT according to pt BW (<60 kg vs ≥60 kg). Tumors were assessed using mRECIST, by independent radiologic review. Results: In Study 202, pts in the <60 kg group had a median treatment duration of 5.8 mos and received 57% of the LEN planned starting dose (PSD); pts in the ≥60 kg group had a median treatment duration of 9.4 mos and received 78.6% of the LEN PSD. Among Japanese pts in REFLECT, median treatment duration was 5.7 mos in both treatment groups; pts in the LEN 8 mg group received 79.1% of the PSD and pts in the LEN 12 mg group received 70.7% of the PSD. In Study 202, treatment-related adverse events (TRAEs) led to dose reduction in 80.8% of pts in the <60 kg group and 55% of pts in the ≥60 kg group. In REFLECT, TRAEs led to dose reductions in 52.5% of pts in the LEN 8 mg group and 70.7% of pts in the LEN 12 mg group. Serious TRAEs occurred at incidences of 46.2% and 10.0% in Study 202 in the <60 kg and ≥60 kg groups, and 15.0% and 22.0% in REFLECT in the LEN 8 mg and LEN 12 mg groups, respectively. Efficacy results are in the Table. Conclusions: Despite the small sample size, this comparison of Study 202 pts and Japanese pts from REFLECT indicates that BW-adjusted LEN dosing in pts with uHCC yielded comparable efficacy between pts <60 kg who received LEN 8 mg and pts ≥60 kg who received LEN 12 mg. The safety profile was favorable in pts <60 kg who received LEN 8 mg in REFLECT vs those who received LEN 12 mg in Study 202. Fewer serious TRAEs and dose reductions due to TRAEs were observed in pts with lower BW who received the LEN 8 mg starting dose in REFLECT. These data suggest that by reducing the starting dose from LEN 12 mg to 8 mg in pts with uHCC and lower BW (<60 kg), safety is improved without compromising efficacy. Clinical trial information: NCT00946153; NCT01761266. [Table: see text]

Characterization of long-term responders following treatment with talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 embraca trial.

1029 Background: In the EMBRACA trial (NCT01945775), the poly(ADP-ribose) polymerase inhibitor (PARPi) TALA significantly improved progression-free survival (PFS) versus PCT in patients (pts) with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (BC) (8.6 vs 5.6 months [mo]; hazard ratio [HR, 95% CI] 0.54 [0.41-0.71]; P < 0.0001). Predictive markers for response to PARPi, other than germline BRCA1/2 mutational status, are largely unknown. A previous analysis investigated biomarkers associated with long and short responders in EMBRACA. Here, we report the clinical characteristics of long and short responders. Methods: Pts were randomized 2:1 to TALA or PCT. In this retrospective analysis, pts in the intent-to-treat (ITT) population were mapped into two groups based on response: LONG (pts in TALA arm with overall survival [OS] ≥30 mo and duration of treatment ≥24 mo; pts in PCT arm with OS ≥30 mo); SHORT (pts in either arm with a PFS event [progressive disease by Independent Radiological Facility or death] ≤12 wks). Data cutoff date was Sept 30, 2019. Results: Of 431 pts randomized, 412 pts were treated (286 received TALA; 126 received PCT). In the ITT population, 37 pts receiving TALA and 34 pts receiving PCT were identified as LONG responders; 40 pts receiving TALA and 32 pts receiving PCT were SHORT responders. The Table shows a summary of pt characteristics for LONG and SHORT responders. More pts with HR+ BC and no prior CT for ABC were associated with LONG response; more pts with TNBC and ≥2 prior CT regimens or platinum were associated with SHORT response (Table). Median treatment duration for LONG responders (n = 37, TALA; n = 31, PCT) was 33.5 (24.0-61.4) mo for TALA and 7.6 (1.1-36.3) mo for PCT; 51.4% receiving TALA and 91.2% receiving PCT had subsequent therapy. In SHORT responders, median treatment duration was 2.0 (0.1-5.5) mo (TALA) and 1.4 (0.2-5.6) mo (PCT); 67.5% and 68.8% received subsequent therapy following TALA or PCT, respectively. Conclusions: In this clinical characterization of responders from the EMBRACA study, a higher number of LONG responders had HR+ BC and received no prior CT for ABC. A greater proportion of SHORT responders had TNBC and received ≥2 prior CT regimens or platinum. Further investigation is warranted in a larger number of pts. Clinical trial information: NCT01945775 .[Table: see text]

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Novel Therapies in Routine Clinical Practice in Germany

Background: To better understand the clinical practice in Germany with respect to the rapidly evolving treatment landscape, we aim to describe the characteristics and treatment patterns of patients (pts) with relapsed/refractory multiple myeloma (RRMM) in Germany. Methods: In a national retrospective medical chart review including consecutive pts treated for RRMM in participating hospitals/centers and practices across Germany between Oct 2017 and Jun 2018, the following data were extracted from Oct 2019 to Feb 2020: pt demographics, disease characteristics, treatment history at MM diagnosis and at initiation of RRMM therapy, and distance to care. Physician's assessment of response to therapy and minimal residual disease (MRD) testing were also collected. Because this analysis was not powered to compare between regimens or lines of therapies, results are purely descriptive. Results: Physicians from 47 participating centers extracted 484 pt charts, that included 214 pts (44%) in 2nd line of therapy (2L), 160 (33%) in 3rd line (3L) and 110 (23%) in 4th line and beyond (4L+) (Figure 1). Half of the participating centers were office-based (52%) and 40% were hospitals. Results are summarized in Table 1 and regimens described by line of therapy in Figure 2: Among the 2L subgroup (N=214), median age was 72 years and the majority (73%) of pts had an ECOG status of 0-1 at 2L initiation. About one-third (31%) of pts had had a transplant. Carfilzomib (CFZ) or daratumumab (Dara)-based regimens were mainly used in 2L pts (40% and 41%, respectively). Among the 87 Dara pts, the triplet regimen Dara, lenalidomide (LEN) and dexamethasone (DRd) was used in more pts (58%) than the triplet with Dara, bortezomib (BTZ) and dexamethasone (DVd, 15%). Among the 85 CFZ pts, nearly half (47%) received the triplet regimen CFZ, LEN and dexamethasone (KRd) and 38% of CFZ pts received the doublet of CFZ and dexamethasone (Kd). Among the remaining 42 pts in 2L, other LEN use was described in 35 pts and BTZ in 7 pts. For 107 pts who completed 2L, median treatment duration was 8 months (9 months for CFZ pts; 8.5 months for Dara pts; 6 months for LEN pts). Where response was available (n=191/214), a complete response (CR) or very good partial response (VGPR) was achieved by 64% of pts, including 73% of Dara pts (n=53/73), 62% of CFZ pts (n=48/78), and 53% of LEN pts (n=18/34). 149 ptssteoprotective drugs at 2L initiation, mainly intravenous zoledronate (ZA, 44%) and subcuteaneous denosumab (Dmab, 42%). In the 3L subgroup (N=160), median age was 72 years. Over half (58%) of pts had an ECOG status of 0-1 at 3L initiation. Most 3L pts received Dara (51%, n=81) or CFZ (35%, n=57), and a further 9% (n=15) of 3L pts received other LEN combinations. In 3L, CFZ was more often used as a doublet (54% Kd vs. 28% KRd); Dara was mainly given in triplet regimens (23% DRd, 17% DVd vs. 12% Dara mono). For 118 pts who had completed 3L at time of data extraction, median treatment duration was 10 months (10 months for both CFZ and Dara pts, 7 months for LEN pts). Where response was available (n=139), CR/VGPR was achieved by 55% of pts in 3L, including 64% of Dara pts (n=46/72) and 41% of CFZ pts (n=20/49). Osteoprotective drugs (51% Dmab, 36% ZA) at 3L initiation were given in 69% (n=111) of pts. In the 4L+ subgroup (N=110), median age was 74 years. A high percentage (64%) of pts had an ECOG status ≥2 at 4L initiation. Over half (52%, n=57) received Dara, mostly as monotherapy (70% Dara; 9% DRd, 2% DVd), followed by CFZ in 26% (n=28) and pomalidomide (POM) in 16% (n=18) of pts in 4L+. For 97 pts who completed 4L at time of data extraction, median treatment duration was 8 months (9 months for both CFZ and Dara pts, 7 months for POM pts). Where response was available (n=106), 39% of pts achieved a CR/VGPR, including 46% of Dara pts (n=25/55) and 36% of CFZ pts (n=10/28). At 4L initiation, 66% (n=72) of pts were receiving osteoprotective drugs (51% Dmab, 40% ZA). Conclusion: This chart review indicates that pts with RRMM who underwent a MM therapy between Oct 2017 and Jun 2018 in routine practice across Germany, mostly received combination regimens with novel agents irrespective of the line of therapy. Lenalidomide is still often combined with novel agents. Patterns of treatment regimens differed by line of therapy and are adapted as disease progresses and ECOG status increases. Disclosures Steinmetz: Amgen; BMS, Celgene, Novartis; Janssen-Cilag; Omnicare, Vifor: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Alexion, Amgen, Bayer, BMS, Boehringer, Celgene, Janssen-Cilag, Novartis, Omnicare, Sanofi, Takeda: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; DGHO, ESMO, DGPM, BNHO, NIONo: Other: Memberships; Alexion, Accord Healthcare, Amgen; Ariad, Bluebird Bio, BMS, Boehringer, Celgene, Hexal-Sandoz, Novartis; Janssen-Cilag; Omnicare, Oncopeptides, Otsuka, Pfizer, Sanofi, Shire, TAD, Takeda, Vifor: Consultancy; Accord Healthcare, Amgen, Celgene, Novartis, Vifor: Research Funding. Singh:Amgen Ltd, UK: Current Employment. Milce:Amgen: Research Funding; Kantar Health, France: Current Employment. Haidar:Kantar Health, France: Current Employment; Amgen: Research Funding. Rieth:Amgen GmbH, Germany: Current Employment; Amgen: Current equity holder in private company. Lebioda:Amgen GmbH, Germany: Current Employment; Amgen: Current equity holder in private company.

278. Comparison of Oral Cephalexin Versus Oral Levofloxacin for Treatment of Uncomplicated Enterobacterales Bacteremia

Background Aerobic gram-negative rods (GNR) are a common cause of bloodstream infections. While the use of oral antibiotics as step-down therapy for GNR bacteremia is generally accepted, there is debate as to which agents are best. Fluoroquinolones have high oral bioavailability but also have concerns for toxicity, while oral beta-lactams have lower achievable blood concentrations and require more frequent dosing. At Kaweah Delta Medical Center, patients are transitioned from IV antibiotics to oral levofloxacin or cephalexin. The purpose of this study is to determine if these two oral agents are comparable when used as step-down therapy for uncomplicated GNR bacteremia. Methods This was a single-center, retrospective study of adult patients who were admitted from May 2018 - May 2019 with a positive GNR blood culture. The primary objective was to assess treatment failure defined as a composite outcome of readmission due to recurrent bacteremia or mortality within 60-days. Secondary outcomes included subsequent Clostridioides difficile infection, emergence of resistant GNR bacteria, and hospital length of stay. Results A total of 82 patients met inclusion criteria. The combined median age of both treatment groups was 58.2 years (interquartile range [IQR], 46.7–73.5) and greater than 60% of patients were female. Most patients were Hispanic (45.1%) or non-Hispanic white (43.9%). The most common documented source of GNR bacteremia was the urinary tract (74.4%), and the most frequently recovered organism was Escherichia coli (78.0%). Patients were treated with IV antibiotics for a median treatment duration of 4 days (IQR, 4–5) and oral antibiotics for a median treatment duration of 10 days (IQR, 7.3–11) and 9 days (IQR, 7–11) for cephalexin and levofloxacin, respectively. The composite outcome occurred in 2 patients (4.3%) from the cephalexin group and 0 patients from the levofloxacin group (p=0.50). Positive cultures for resistant GNR were found for 3 patients in the cephalexin group. No patients developed subsequent C. difficile infections. Conclusion Patients who received cephalexin or levofloxacin did not have a significant difference in the composite primary outcome. These findings suggest that oral cephalexin is an effective step-down option to treat uncomplicated GNR bacteremia. Disclosures All Authors: No reported disclosures

Safety and efficacy of BAY1436032 in IDH1-mutant AML: phase I study results

The mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing. Most subjects experienced only partial target inhibition as indicated by plasma R-2HG levels. BAY1436032 was safe and a maximum tolerated dose was not identified. The median treatment duration for all subjects was 3.0 months (0.49–8.5). The overall response rate was 15% (4/27; 1 CRp, 1 PR, 2 MLFS), with responding subjects experiencing a median treatment duration of 6.0 months (3.9–8.5) and robust R-2HG decreases. Thirty percent (8/27) achieved SD, with a median treatment duration of 5.5 months (3.1–7.0). Degree of R-2HG inhibition and clinical benefit did not correlate with dose. Although BAY1436032 was safe and modestly effective as monotherapy, the low overall response rate and incomplete target inhibition achieved at even the highest dose tested do not support further clinical development of this investigational agent in AML.

A first-in-human phase I/II study of HL-085, a MEK Inhibitor, in Chinese patients with NRASm advanced melanoma.

10047 Background: MEK inhibitors have confirmed effects on malignant tumors, especially for those induced by RAS/RAF dysfunction. There is no effective drug in clinic for NRASm advanced melanoma. HL-085 is a selective MEK inhibitor, showing good safety and efficacy in preclinical studies. This study is a phase I/II study to evaluate the safety, tolerability, pharmacokinetic and preliminary anti-cancer activity of HL-085 in patients(pts) with NRASm advanced Melanoma. Methods: The phase I/II study is conducted using a “3+3” regimen for dose escalation. The pts are treated with HL-085 at a starting dose of 0.5mg BID to 18mg BID. Adverse events (AEs) are reported per NCI CTCAE version 5.0. Preliminary anti-cancer activity is evaluated by ORR, DCR, PFS and DoR. Results: Total 33 pts were enrolled in the study. The histologic types were acral (51.4%), mucosal (27.2%) and other (21.2%). The NRAS mutation types were Q61 (72.7%), G12 (18.2%) with half for G12D, and G13 (9.1% ). Most AEs were G1 or G2, and the most common drug-related AEs were rash, increased creatine phosphokinase, peripheral edema, increased alanine aminotransferase and aspartate aminotransferase. No dose-limited toxicity was observed. PK analysis was shown linear PK profile with no obvious accumulation. Among 12 evaluable pts over 9 mg, 4 pts were at the stage of M1c with 1 liver metastasis. Average targeted tumor size was 74.6mm with the largest 184 mm. 10 pts achieved tumor shrinkage [ 60% with Q61, 20% with G12D, 10% each with G12S and G13R]. 4 pts ( 2 acral, 1 mucosal and 1 other, each pt has mutaiton type of Q61R,Q61L, Q61K and G12S respectively ) had confirmed partial response(PR) [median treatment duration 26.6 weeks (wks) with longest 47.6 wks]). 6 pts achieved stable disease (SD) (median treatment duration 15.72 wks with longest 24 wks), and 66.7% were over 14 wks . The median PFS was 17.4 wks, and confirmed best ORR was 33.3% with DCR 83.3% . Conclusions: Our data demonstrated that HL-085 is well tolerated, with manageable side-effects and promising anti-cancer activity in pts with NRASm advanced melanoma. Clinical trial information: NCT 03973151.

Landmark analysis of immunotherapy duration and disease free survival in advanced melanoma patients with a complete response.

10054 Background: Checkpoint blockade improves survival in patients with melanoma, with durable complete responses (CR) after stopping therapy. Based on data from KEYNOTE-001, immunotherapy is often continued for 24 months in patients with confirmed CR. Outcomes with treatment of less than 24 months hav not been adequately evaluated and reported. If equally efficacious, shorter courses would potentially reduce health care costs and toxicity. Methods: 45 patients with locally advanced stage III and IV melanoma who received immunotherapy (pembrolizumab, nivolumab or ipilimumab/nivolumab) as 1st line or subsequent therapy, achieved a CR, and stopped therapy were identified under an IRB approved protocol at Penn. Disease Free Survival (DFS) was defined as time from declaration of CR until recurrence or date of analysis (1/15/20). Landmark DFS from time of CR was analyzed based on duration of therapy (less than or greater than 7 months, based on early trial requirements to treat patients with confirmed CR for at least 6 months). Rationale for stopping (toxicity or CR) was also analyzed. Results: Of 45 patients with CR, 27 (60%) were treated less then 7 months (median 4.8, range 1 day to 6.7 months) and 18 (40%) were treated for greater than 7 months (median 12.4, range 7.5 to 24.2 months). Patients who were treated for less than 7 months had a median DFS from time of CR of 30.4 months (95% CI 23.7 to 37.2, range 2.9 to 65.7 months). Patients treated for greater than 7 months had a median DFS of 28.0 months (95% CI 18.9 to 37, range 8.5 to 73.7 months). Patients who stopped due to toxicity (N = 17, 40%) had a median treatment duration of 3.7 months. Their median DFS from time of CR was 30.4 months (95% CI 20.7 to 40.1, range of 2.9 to 65.7 months). Patients who stopped due to CR (N = 28, 60%) had a median treatment duration of 8.5 months. Their median DFS was 27.6 months (95% CI 21.2 to 34 range 7.2 to 73.7 months). Two of 27 (7.4%) patients treated for less then 7 months and 3 out of 18 (16%) patients treated greater than 7 months recurred after stopping. One out of 17 (5.8%) recurred after stopping for toxicity vs. 4/28 (14.3%) who stopped after CR. Conclusions: Patients who stop therapy at less than 7 months have CRs that are equally durable as those treated longer than 7 months, without reduction in landmark DFS. Patients who stopped therapy due to toxicity and then achieved a CR had no difference in DFS compared to patients treated until CR. There was no significant difference in recurrence after achieving a complete response in patients treated for a longer vs shorter treatment course.

P278 Real-world experience with an IL-17A blocker in biologic-naïve and biologic-experienced radiographic and non-radiographic axSpA patients

Background In Europe, IL-17A blocker secukinumab is approved for ankylosing spondylitis (AS). The label dose is 150mg: loading dose regimen at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. 300mg dose is not indicated for AS. Secukinumab is not yet approved for non-radiographic axial spondyloarthritis (nr-axSpA). Objectives: Describe real-world dose utilization of an IL-17A blocker among axial spondyloarthritis (axSpA) patients with radiographic (AS) and nr-axSpA. Methods Descriptive, cross-sectional survey of physicians managing axSpA (France, Germany, Italy, Spain, UK, Austria & Australia). At the time of survey (April-August 2019), only secukinumab was approved. Physicians completed patient record forms for their next 7 consulting patients currently treated with or discontinued secukinumab, recording demographics, disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI), Ankylosing Spondylitis Disease Activity Score, ASDAS) and treatment history. Results 275 rheumatologists and 4 orthopedists provided data for 2,101 patients: 1,509 (1151 AS; 358 nr-axSpA) currently receiving secukinumab and 592 (385 AS; 207 nr-axSpA) secukinumab discontinuers. Mean age was 45.1years (45.8 AS; 43.2 nr-axSpA), 64.4% were male (68.8% AS, 52.4% nr-axSpA), and mean time diagnosed was 5.3years (5.9 AS; 3.8 nr-axSpA). 50.5% (48.4% AS; 55.9% nr-axSpA) of patients were receiving secukinumab as their first biologic, 48.4% biologic-experienced. 94.1% (93.9% AS; 94.3% nr-axSpA) of all users were treated beyond loading dose phase of secukinumab; 8.8% dose up-titrated from 150mg to 300mg. Of patients currently receiving secukinumab maintenance, median treatment duration was 44.4weeks (n = 1249). 71.5% (71.4% AS; 72.3% nr-axSpA) received 150mg monthly, 28.5% received a dose outside label (23.7% on 300mg). For discontinuers who reached maintenance phase, median treatment duration was 20.0weeks (n = 547). 38.7% (37.4% AS; 41.3% nr-axSpA) of secukinumab discontinuers received a dose outside label (33.9% on 300mg). 30.5% (28.8% AS; 36.1% nr-axSpA) of biologic-experienced patients received secukinumab 300mg. The utilization of secukinumab 300mg in biologic-experienced discontinuers was 36.9% and higher than in current biologic-experienced users (28.0%). At initiation of secukinumab 150mg, 95.1% and 90.7% of patients had BASDAI≥4 (n = 593) and ASDAS≥2.1 (n = 129), respectively. For those continuing, after a median duration of 42.3weeks, 31.7% (30.4% AS; 35.7% nr-axSpA) had BASDAI≥4 and 30.2% (27.8% AS; 37.5% nr-axSpA) ASDAS≥2.1. At initiation of secukinumab 300mg, 93.1% and 96.4% had BASDAI≥4 (n = 173) and ASDAS≥2.1 (n = 28), respectively. For those continuing, after median duration of 51.9weeks, 42.2% (38.2% AS; 54.8% nr-axSpA) had BASDAI≥4 and 57.1% (52.4% AS; 71.4% nr-axSpA) ASDAS≥2.1. Conclusion In the real-world, secukinumab discontinuation occurred after 20.0weeks, despite approximately one third being treated with secukinumab 300mg. For those remaining on secukinumab, up to 30% used outside-label doses (higher in biologic-experienced patients). Secukinumab is not universally prescribed for the approved indication or at the recommended dose. There is a suggestion that not all patients receiving a higher dose achieve low disease activity. Disclosures N. Booth: Grants/research support; Research was funded by eli-lilly and company. Other; Employed by Adelphi Real World. J. Hill: Other; Employed by Eli Lilly and company. S. Leage: Other; Employed by Eli Lilly and company. C. Sapin: Other; Employed by Eli Lilly and company. E. Holdsworth: Other; Employed by Adelphi Real World. S. Antonelli: Other; Employed by Eli Lilly and company.

Real-World Treatment Patterns and Transfusion Burden Among US Patients with Newly Diagnosed Myelodysplastic Syndromes (MDS)

Introduction: Symptomatic anemia transfusion support represents a significant problem for patients with MDS. The principal strategy in managing these patients remains supportive care with erythropoiesis-stimulating agents (ESAs) and red blood cell (RBC) transfusions. However, there is paucity of real-world data regarding patterns of use of ESA and other therapies, and its impact on transfusion needs in these patients early in their clinical course. To address this question, we performed a retrospective claims-based study to characterize treatment patterns and transfusion burden in patients with MDS. Methods: In this retrospective claims analysis of a large national health insurance plan, all patients aged ≥ 18 years with newly diagnosed MDS (≥ 2 medical claims with an International Classification of Diseases, 9th or 10th Revision [ICD-9 or ICD-10] diagnosis codes ≥ 30 days apart) identified between January 2012 and May 2018 were included. Index date was defined as date of first diagnosis. Continuous health plan enrollment for ≥ 6 months pre- and 3 months post-index date was required. RBC transfusion status was evaluated during the 16 weeks prior to first diagnosis as well as 16 weeks prior to and immediately following line of therapy (LOT) 1 and LOT2. Transfusion burden categories were adapted and modified from the proposed International Working Group 2018 revised criteria (Platzbecker U, et al., Blood. 2019;133(10):1096-1107). Categories included transfusion independence (TI), defined as patients receiving no transfusions during the observation period; low (LTB), moderate (MTB), and high transfusion burden (HTB) were defined by patient's having 1-3, 4-7, and ≥ 8 unique dates for a transfusion during the observation periods, respectively. Therapies in each LOT were captured using pharmacy and medical claims data. The end of a LOT was defined after ≥ 60-day gap in therapy, a claim for any new or additional MDS therapy, or patient death; LOT durations are described for non-censored patients. Results: Among the 3,587 patients identified (mean age = 74.9 years, 44.3% female), transfusion burden during 16 weeks prior to index was: 78.8% TI, 19.2% LTB, 1.9% MTB, and 0.2% HTB. Among the 1,935 patients who received LOT1, transfusion burden in the 16 weeks preceding LOT1 was: 57.0% TI, 36.3% LTB, 5.6% MTB, and 1.1% HTB. The top 5 regimens in LOT1 were ESA monotherapy (61.9%), hypomethylating agent (HMA) monotherapy (19.2%), white blood cell growth factor (WBCGF) monotherapy (3.5%), immunomodulators (3.3%), and HMA + ESA (2.7%) (Figure). Of 824 patients who received LOT2, transfusion burden prior to LOT2 was: 49.4% TI, 28.6% LTB, 16.5% MTB, and 5.5% HTB. The top 5 regimens in LOT2 were ESA monotherapy (44.2%), HMA monotherapy (12.1%), HMA + ESA (9.2%), WBCGF + ESA (6.9%), and WBCGF monotherapy (6.4%) (Figure). In LOT1, the median treatment duration for ESA monotherapy was 2.8 months (mean = 5.2 months, standard deviation [SD] = 6.8) whereas in LOT2, the median treatment duration was 2.0 months (mean = 3.7 months, SD = 5.0). Amongst patients receiving ESA monotherapy as LOT2, 90.4% had prior ESA monotherapy as LOT1. In patients treated with HMA monotherapy in LOT1 that also experienced a LOT2, 39.1% moved on to a variety of LOT2 regimens (Table), while in 15.5% ESAs were combined with HMA (Table). Conclusions: Our results show that at the time of diagnosis, 20% of MDS patients were transfusion dependent, but up to 50% require treatment. The high rate of ESA use is likely due to anemia-related symptoms. In those treated with ESA monotherapy, approximately 50% have a LOT1 duration that is &lt; 3 months, and interestingly, the majority of patients restart a second LOT with an ESA as the most common regimen. Additional analyses are necessary to determine whether this indicates a switch in ESA agent, escalation in dose of prior ESA, treatment cycling due to elevated hemoglobin, or other reasons. Considering the short median treatment duration and worsening of transfusion dependency beyond first line, there remains a high unmet need for MDS therapy that more effectively slows the progression of transfusion dependence. Disclosures Mukherjee: Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor. Slabaugh:Celgene Corporation: Employment, Equity Ownership. Copher:Celgene Corporation: Employment. Johnson:Optum: Employment; Celgene Corporation: Consultancy. Buzinec:Optum: Employment. Mearns:Celgene Corporation: Employment.

Discontinuation Patterns in Patients Receiving Novel Oral Agents for Chronic Lymphocytic Leukemia in the Veterans Health Administration

Introduction Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, accounting for 25-30% of all leukemias in the United States. During the past decade, there has been a paradigm shift in CLL treatment, with increasing adoption of novel oral agents (NOAs) such as acalabrutinib (ACALA), duvelisib (DUV), ibrutinib (IBR), idelalisib (IDELA), and venetoclax (VEN) instead of traditional chemoimmunotherapy (CIT). Unlike CIT, most NOAs are given daily for an indefinite period of time and are self-administered at home, raising concerns about adherence and discontinuation. The discontinuation patterns of NOAs in a real-world population of CLL patients is currently unknown. Methods Using the Veterans Administration (VA) Cancer Registry System and electronic healthcare records, we identified patients treated for CLL with NOAs in the VA from November 1, 2013 to November 30, 2018. Patients were followed from the first NOA dispensation until death or the end of the study observation (May 31, 2019). NOAs were selected in accordance with the National Comprehensive Cancer Network (NCCN) guidelinesfor CLL and were extracted using pharmacy dispensation records. Discontinuation was defined as the absence of NOA dispensation within 60 days of estimated exhaustion of patient's NOA supply from the last recorded dispensation. A discontinuation event for each NOA treatment episode in each patient was classified as either 1) a drug holiday, if there was evidence of resumption of the same treatment without any other treatment interventions after the first discontinuation; or 2) permanent discontinuation, in which the treatment ceased without evidence of resumption for 60 days or there was evidence of new treatment initiation after the discontinuation of previous treatment. We report the proportion of discontinuation and exposure-adjusted discontinuation rates (e-AR), which were calculated using the length of NOA duration in person-time. Results We identified 1,196 CLL patients treated with NOAs from November 1, 2013 to November 30, 2018. The mean age at NOA initiation was 70.7 years; 96.7% of patients were male. The median time from diagnosis to NOA initiation was 56.5 months (0-189.5 months). Of the 1,196 patients treated with NOAs, 1,172 received IBR, 53 received IDELA, and 106 received VEN. There were few patients (<10)treated with ACALA and DUV, therefore these patientswere omitted from the final analyses. During a median follow-up of 18.9 months (0-65.3 months), 48.2% NOA treatment courses were followed by a discontinuation event. The proportions of patients who discontinued for IBR, IDELA, and VEN were 47.5%, 77.4%, and 41.5%. The e-AR of IBR, IDELA, and VEN are reported in Table 2. At the end of the study observation (May 2019), 52.6% of IBR, 22.6% of IDELA, and 58.3% of VEN treatment courses were still being administered. In first-line (L1) IBR, the median NOA treatment duration until the first discontinuation was 10.7 months (0.8-55.8 months), 12.6 months (0.5-62.0 months) in second-line (L2) IBR, and 12.2 months (0.78-57.8 months) in third-line or subsequent lines (L3+) IBR. In IDELA treatment courses, the median treatment duration until the first discontinuation was 17.8 months (1.9-41.6 months) in L2 and 4.3 months (1.7-26.2 months) in L3+. In VEN, the median treatment duration until the first discontinuation was 8.4 months (3.1-26.0 months) in L2 and 7.4 months (1.7-18.5 months) in L3+. Of 532 L1 IBR treatment courses with >1 dispensation, 96 (18%) were associated with a drug holiday and 97 (18%) with permanent discontinuation. These numbers were 64 (27%) and 50 (21%) for L2 IBR courses, and 90 (28%) and 76 (24%) for L3+ IBR courses. Similarly, 24 (67%) of L3 IDELA treatment courses with >1 dispensation were associated with permanent discontinuation. Among 63 L3+ VEN courses with >1 dispensation, 6 (10%) were associated with a drug holiday and 14 (22%) with permanent discontinuation. Conclusions To our knowledge, this study is the first to report on the NOA discontinuation in a nationwide VA cohort of CLL patients treated in a real-world setting. Our results suggest there is a substantial proportion of drug holidays and permanent discontinuation among commonly used NOAs. Further efforts will focus on understanding factors leading to discontinuation and the impact of discontinuation/drug holidays on clinical outcomes. Disclosures Biondo: Genentech, Inc.: Employment; F. Hoffmann-La Roche Ltd: Equity Ownership. Halloran:Roche: Equity Ownership; Genentech, Inc.: Employment. Shapouri:Roche: Equity Ownership; Genentech, Inc.: Employment. Wu:Genentech, Inc.: Employment. Sauer:University of Utah and SLC VA Medical Center: Employment. Halwani:Miragen: Research Funding; Kyowa Hakko Kirin: Research Funding; Pharmacyclics: Research Funding; Amgen: Research Funding; Seattle Genetics: Research Funding; Genentech, Inc.: Research Funding; AbbVie: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Immune Design: Research Funding.