Health Resource Utilization and Costs Associated with the Use of Obinutuzumab-Based Regimens Are Similar to Rituximab-Based Regimens for the First-Line Treatment of Follicular Lymphoma

Introduction: Obinutuzumab (GA101; G), a fully humanized, glycoengineered, type II anti-CD20 monoclonal antibody, is approved in the US for the first-line (1L) treatment of follicular lymphoma (FL). Despite the superior efficacy of G plus chemotherapy (G-chemo) versus rituximab (R) plus chemotherapy (R-chemo) in patients with previously untreated FL demonstrated in the Phase III, randomized GALLIUM study (NCT01332968; Marcus et al. N Engl J Med 2017), information on healthcare resource use (HRU) and real-world costs with G in previously untreated FL patients is limited. The aim of this retrospective cohort study was to examine HRU and costs for G-based and R-based therapies for the 1L treatment of FL using a US claims database. Methods: The data source for this study was the PharMetrics Plus Commercial Claims database. Adult patients (≥18 years) diagnosed with FL between February 1, 2015 and September 30, 2018 and who began any treatment for FL between February 1, 2016 and September 30, 2018 were included. The first FL treatment date within this selection window was denoted the index date. Patients were required to have ≥12 months of pre-index and ≥3 months of post-index continuous study enrolment, and to have at least one FL diagnosis on or during the 12-month pre-index period. Patients with FL treatment during the 12-month pre-index period were excluded in order to select only previously untreated patients. HRU and cost data during the 1L treatment period were descriptive and categorized by HRU category. Costs are in 2018 US dollars ($) and standardized as per patient per month (PPPM) costs. FL treatment determination was based on National Comprehensive Cancer Network guidelines. Results: A total of 1584 FL patients with ≥3 months follow up were analyzed. Overall, 26 patients received G-chemo (any combination) as their 1L treatment, 208 patients received R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), 391 patients received R-Benda (bendamustine) and 17 patients received R-CVP (cyclophosphamide, vincristine, prednisone); the remaining 942 patients received other regimens (predominantly other R combinations). Data are reported for those patients who received G-chemo, R-CHOP, R-Benda or R-CVP as 1L therapy (n=642; 281 females, 361 males). Baseline patient characteristics were similar for most variables across treatment groups. Mean (standard deviation [SD]) age was 56.9 (9.7) years and all patients had a Charlson Comorbidity Index (CCI) of ≥2 (mean [SD]: 2.9 [1.9]). Mean (SD) patient follow-up was 14.1 (8.0) months and mean (SD) duration of 1L treatment was 7.0 (5.1) months. A summary of all-cause HRU in patients receiving 1L treatment is provided by treatment category (Figure 1A). The proportion of patients with at least one hospitalization was highest with R-CHOP (23.6%). The proportion of patients with at least one emergency room (ER) visit was highest with R-Benda (29.4%). Mean (SD) total all-cause healthcare costs PPPM during 1L treatment were comparable among G-chemo, R-CHOP and R-Benda (Figure 1B) and lowest with R-CVP ($17,874 [$13,465]). Medical costs (mean [SD]) were highest for R-Benda ($27,716 [$19,610] PPPM) and lowest for R-CVP ($17,373 [$12,908] PPPM). G-chemo was associated with the lowest pharmacy costs ($76 [$107] PPPM) (Figure 1B). Mean (SD) total cost of FL drug treatment PPPM was $16,028 ($9,942) for G-chemo, $11,684 ($6,122) for R-CHOP and $12,108 ($8,794) for R-CVP. Mean (SD) total cost of FL drug treatment PPPM was highest with R-Benda ($21,263 [$15,328]). G-specific drug costs PPPM ($9,643 [$6,071]) were similar to R-specific drug costs ($9,992 [$5,234] R-CHOP; $9,083 [$5,859] R-Benda; and $10,702 [$7,717] R-CVP). Conclusions: Our results depict real-world HRU and costs associated with G and commonly used 1L regimens for FL. In this setting, HRU and costs associated with G-chemo were comparable with R-chemo, supporting the use of G-chemo as a treatment option for patients with previously untreated FL. The study findings are limited by the small sample size of the G-chemo patient cohort (n=26) and short follow-up; to address this, an updated analysis incorporating a larger number of patients is planned. Disclosures To: Genentech, Inc.: Employment, Equity Ownership. Dawson:Roche/Genentech: Equity Ownership; Genentech: Employment. Masaquel:Genentech: Employment; Roche: Equity Ownership. Seetasith:Genentech: Employment, Equity Ownership.

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Treatment Patterns and Outcomes of Patients with Relapsed or Refractory Follicular Lymphoma Treated with Idelalisib in a Community Oncology Setting

Blood ◽

10.1182/blood-2019-124013 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2810-2810

Author(s):

David Andorsky ◽

Rebecca J Chan ◽

Jamyia Clark ◽

Bianca Ruzicka ◽

Nicholas James Robert ◽

...

Keyword(s):

Clinical Trial ◽

Follicular Lymphoma ◽

Real World ◽

Research Funding ◽

Treatment Patterns ◽

Employment Equity ◽

Real World Setting ◽

Equity Ownership ◽

Systemic Therapies

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.

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Disease Characteristics, Treatment Patterns, and Outcomes of Follicular Lymphoma in Patients 40 Years of Age and Younger: An Analysis from the National LymphoCare Study

Blood ◽

10.1182/blood.v124.21.3044.3044 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3044-3044 ◽

Cited By ~ 1

Author(s):

Carla Casulo ◽

Michelle Byrtek ◽

Keith L Dawson ◽

Xiaolei Zhou ◽

Christopher R. Flowers ◽

...

Keyword(s):

Follicular Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Watchful Waiting ◽

First Line ◽

Employment Equity ◽

Advisory Committees ◽

Disease Characteristics ◽

Equity Ownership

Abstract Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the world and has a median age at diagnosis in the seventh decade. FL in young adults (YA; 40 years old or younger) is extremely rare. Currently, there are no standard approaches guiding treatment of YA patients with FL, and very little is known about disease characteristics and outcomes of YA patients with FL given limited research conducted in this vulnerable population. To gain further insight into FL in YA, we analyzed the National LymphoCare Study (NLCS) to describe disease and patient characteristics, as well as features of treatment in YA patients with FL. We previously reported that 2-year progression-free survival (PFS) is an important survival endpoint in patients with FL undergoing chemo-immunotherapy. Hence, we also sought to characterize 2-year PFS in this age group and compare it to older cohorts. Methods: Evaluablepatients were identified in the NLCS, and those between 18–40 years of age with newly diagnosed FL at any stage were classified as YA patients. Patients with mixed histology or transformed disease were excluded, as were patients with progression of disease prior to beginning first-line treatment. Survival probability was estimated by the Kaplan-Meier method. We estimated the association of age group with PFS using hazard ratios (HR) and 95% confidence intervals (CI) from multivariable Cox models. Results: A total of164 YA patients with FL were analyzed, representing 6.2% of the NLCS population, similar to the observed frequency in the Surveillance, Epidemiology, and End Results (SEER) Program data (4.8% of all FL). Sixty nine percent of YA patients had advanced stage disease. The majority of patients (80%) had low-grade histology, and 50% had good risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent of patients (31/164) underwent watchful waiting, 12% received rituximab monotherapy, and 47% received chemo-immunotherapy (61% of whom received R-CHOP [rituximab, doxorubicin, vincristine, prednisone]). There was no significant difference in FLIPI score or other baseline disease characteristics compared to adult patients aged 41–60 years. Eleven deaths occurred among YA with FL; only 5 of these were lymphoma related. Overall survival (OS) at 2 years was 97.4% (95% CI 93.3%, 99.0%), and at 5 years, 93.7% (88.3%, 96.7%), which was similar to patients aged 41–60 (97.2% [96.0%, 98.0%] at 2 years, and 92.0% [90.1%, 93.5%] at 5 years). After a median follow-up of 7.1 years, OS in YA FL was 92%. Through follow-up, there were 64 PFS events. The estimated 2-year PFS (95% CI) for YA and adults 41–60 was 75.9% (67.1%, 82.6%) and 80.9% (78.1%, 83.4%), respectively. After adjusting for FLIPI score, there was no difference in PFS for YA with FL requiring first-line treatment (excluding watchful waiting) compared to adults aged 41–60 years (HR=0.93; 95% CI 0.69, 1.25), and no difference in OS compared to adults aged 41–60 years (HR=1.19; 95% CI 0.64, 2.23). Conclusions: In the largest cohort of YA patients with FL to date, we found few differences in outcomes compared to patients aged 41–60. FLIPI and other disease characteristics were similar to adults aged 41–60 years. There were no differences between YA FL and adults aged 41–60 in PFS for all treated patients. OS in the YA group of patients with FL was outstanding. YA patients with FL have reassuringly similar outcomes to patients aged 41–60. Fertility preservation and survivorship issues should be taken into consideration when defining management strategies, but otherwise these data support that YA patients with FL should not be approached differently from older adults with the same disease. Disclosures Byrtek: Genentech, Inc.: Employment, Equity Ownership. Dawson:Genentech, Inc.: Employment, Equity Ownership. Zhou:RTI-HS: Employee of RTI-HS, which has research contracts with Genentech Other. Flowers:Seattle Genetics: Consultancy; Spectrum: Consultancy, Research Funding; Sanofi: Research Funding; Abbott: Research Funding; Novartis: Research Funding; OptumRx: Consultancy; Millennium/Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Allos: Consultancy. Farber:Gilead: Speakers Bureau; Janssen/Pharmacyclics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Leukemia Lymphoma Society NJ Chapter: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Speakers Bureau, Stock ownership Other. Cerhan:Genentech, Inc.: LymphoCare Scientific Advisory Board Other. Link:Genentech, Inc.: Consultancy, Scientific Advisory Board for Genentech Other.

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Prognostic Molecular Stratification in Relapsed/Refractory Multiple Myeloma - Results of the Pomalidomide Mukseven (NCT02406222) Biomarker Trial

Blood ◽

10.1182/blood-2019-123640 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4327-4327

Author(s):

James Croft ◽

Andrew Hall ◽

Amy L Sherborne ◽

Katrina Walker ◽

Sidra Ellis ◽

...

Keyword(s):

Multiple Myeloma ◽

Flow Cytometry ◽

T Cell ◽

High Risk ◽

Real World ◽

Research Funding ◽

Unmet Need ◽

Employment Equity ◽

Equity Ownership

Background Treatment of relapsed/refractory multiple myeloma (RRMM) remains challenging as durable remissions are achieved in patient sub-groups only. Identifying patients that are likely to benefit prior to or early after starting relapse treatments remains an unmet need. MUKseven is a trial specifically designed to investigate and validate biomarkers for treatment optimization in a 'real-world' RRMM population. Design In the randomized multi-center phase 2 MUKseven trial, RRMM patients (≥2 prior lines of therapy, exposed to proteasome inhibitor and lenalidomide) were randomized 1:1 to cyclophosphamide (500 mg po d1, 8, 15), pomalidomide (4 mg days 1-21) and dexamethasone (40 mg; if ≥75 years 20 mg; d1, 8, 15, 21) (CPomD) or PomD and treated until progression. All patients were asked to undergo bone marrow (BM) and peripheral blood (PB) bio-sampling at baseline, cycle 1 day 14 (C1D14, on-treatment) and relapse. For biomarker discovery and validation, IGH translocations were profiled by qRT-PCR, copy number aberrations by digital MLPA (probemix D006; MRC Holland), GEP by U133plus2.0 array (Affymetrix), PD protein markers by IHC and PB T-cell subsets by flow cytometry for all patients with sufficient material. Primary endpoint was PFS, secondary endpoints included response, OS, safety/toxicity and biomarker validation. Original planned sample size was 250 patients but due to a change in UK standard of care during recruitment with pomalidomide becoming available, a decision was made to stop recruitment early. Results In total, 102 RRMM patients were randomized 1:1 between March 2016 and February 2018. Trial entry criteria were designed to include a real-world RRMM population, permitting transfusions and growth factor support. Median age at randomization was 69 years (range 42-88), 28% of patients had received ≥5 prior lines of therapy (median: 3). Median follow-up for this analysis was 13.4 months (95% CI: 12.0-17.5). 16 patients remained on trial at time of analysis (median number of cycles: 19.5; range 8-28). More patients achieved ≥PR with CPomD compared to PomD: 70.6% (95% CI: 56.2-82.5%) vs. 47.1% (CI: 32.9-61.5%) (P=0.006). Median PFS was 6.9 months (CI: 5.7-10.4) for CPomD vs. 4.6 months (CI: 3.5-7.4) for PomD, which was not significantly different as per pre-defined criteria. Follow-up for OS is ongoing and will be presented at the conference. High-risk genetic aberrations were found at following frequencies: t(4;14): 6%, t(14;16)/t(14;20): 2%, gain(1q): 45%, del(17p): 13%. Non-high risk lesions were present as follows: t(11;14): 22%, hyperdiploidy: 44%. Complete information on all high-risk genetic markers was available for 71/102 patients, of whom 12.7% had double-hit high-risk (≥2 adverse lesions), 46.5% single-hit high-risk (1 adverse lesion) and 40.8% no risk markers, as per our recent meta-analysis in NDMM (Shah V, et al., Leukemia 2018). Median PFS was significantly shorter for double-hit: 3.4 months (CI: 1.0-4.9) vs. single-hit: 5.8 months (CI: 3.7-9.0) or no hit: 14.1 months (CI: 6.9-17.3) (P=0.005) (Figure 1A). GEP was available for 48 patients and the EMC92 high-risk signature, present in 19% of tumors, was associated with significantly shorter PFS: 3.4 months (CI: 2.0-5.7) vs. 7.4 (CI: 3.9-15.1) for EMC92 standard risk (P=0.037). Pharmacodynamic (PD) profiling of cereblon and CRL4CRBN ubiquitination targets (including Aiolos, ZFP91) in BM clots collected at baseline and C1D14 is currently ongoing. Preliminary results for the first 10 patients demonstrate differential change of nuclear Aiolos (Figure 1C), with a major decrease in Aiolos H-scores in 7/10 patients from baseline to C1D14 and reconstitution at relapse. T-cell PB sub-sets were profiled at baseline and C1D14 by flow cytometry. Specific sub-sets increased with therapy from baseline to C1D14, e.g. activated (HLA-DR+) CD4+ T-cells, as reported at last ASH. CD4+ T-cell % at baseline was associated with shorter PFS in these analyses in a multi-variable Cox regression model (P=0.005). PD and T-cell biomarker results will be updated and integrated with molecular tumor characteristics and outcome. Discussion Our results demonstrate that molecular markers validated for NDMM predict treatment outcomes in RRMM, opening the potential for stratified delivery of novel treatment approaches for patients with a particularly high unmet need. Additional immunologic and PD biomarkers are currently being explored. Disclosures Croft: Celgene: Other: Travel expenses. Hall:Celgene, Amgen, Janssen, Karyopharm: Other: Research funding to Institution. Walker:Janssen, Celgene: Other: Research funding to Institution. Pawlyn:Amgen, Janssen, Celgene, Takeda: Other: Travel expenses; Amgen, Celgene, Janssen, Oncopeptides: Honoraria; Amgen, Celgene, Takeda: Consultancy. Flanagan:Amgen, Celgene, Janssen, Karyopharm: Other: Research funding to Institution. Garg:Janssen, Takeda, Novartis: Other: Travel expenses; Novartis, Janssen: Research Funding; Janssen: Honoraria. Couto:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Wang:Celgene Corporation: Employment, Equity Ownership. Boyd:Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pierceall:Celgene: Employment. Thakurta:Celgene: Employment, Equity Ownership. Cook:Celgene, Janssen-Cilag, Takeda: Honoraria, Research Funding; Janssen, Takeda, Sanofi, Karyopharm, Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen, Bristol-Myers Squib, GlycoMimetics, Seattle Genetics, Sanofi: Honoraria. Brown:Amgen, Celgene, Janssen, Karyopharm: Other: Research funding to Institution. Kaiser:Takeda, Janssen, Celgene, Amgen: Honoraria, Other: Travel Expenses; Celgene, Janssen: Research Funding; Abbvie, Celgene, Takeda, Janssen, Amgen, Abbvie, Karyopharm: Consultancy.

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Cardiac Events in Real-World Multiple Myeloma Patients Treated with Carfilzomib: A Retrospective Claims Database Analysis

Blood ◽

10.1182/blood.v128.22.3319.3319 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3319-3319 ◽

Cited By ~ 3

Author(s):

Ajai Chari ◽

Sanjay K. Aggarwal ◽

Khalid Mezzi ◽

Kenneth Wang ◽

Christopher Kim ◽

...

Keyword(s):

Real World ◽

Research Funding ◽

Cardiac Event ◽

Index Date ◽

Hospitalized Patients ◽

Cardiac Events ◽

Employment Equity ◽

Claims Database ◽

History Of ◽

Equity Ownership

Abstract Introduction: Multiple myeloma (MM) is a hematologic cancer that mostly affects elderly patients who are at increased risk for development of cardiac-related comorbidities due to age-, disease-, and treatment-related factors. In real world data, approximately 25-30% of MM patients are hospitalized for a cardiac event after MM diagnosis (Kistler et al. American Society Hematology 2012 Annual Meeting, poster 2916). The proteasome inhibitor, carfilzomib, is approved for treatment of patients with relapsed or refractory MM. In carfilzomib clinical trials, grade 3 or higher cardiac failure was reported for ~4% of patients (Stewart et al. NEJM 2015;372:142-52, Dimopoulos et al. Lancet Oncol 2016;17:27-38). In this retrospective analysis, we sought to evaluate the incidence rate (IR) of cardiac events in MM patients treated with carfilzomib in a real-world setting in the US and to describe differences in baseline characteristics between carfilzomib-treated MM patients who do and do not have cardiac events. Methods: Newly-diagnosed MM patients with symptomatic disease were identified in the Truven MarketScan claims database from 1/1/05 to 6/30/15 using an algorithm validated for ascertainment of MM patients in claims data (Princic et al. Blood 2015;126:4521). All carfilzomib-treated patients were included in the analysis. The first dose of carfilzomib was the index date. The baseline period was 12 months prior to the MM diagnosis date to the index date. Cardiac events (hypertension, heart failure, ischemic heart disease, arrhythmias and conduction disorders, and cardiomyopathy) were identified during baseline by inpatient (IP) or outpatient (OP) claims and after index date by primary diagnosis on IP claims (hospitalized events). Logistic regression was used to estimate baseline covariates associated with any cardiac event. Due to sample size constraints, multivariate regression was not performed. The incidence rate (IR) per 1000 patient-years (PYRs) and associated 95% confidence interval (CI) of hospitalized cardiac events during carfilzomib treatment which included 30 days after the last carfilzomib dose were calculated among patients without a history of the corresponding hospitalized event during the baseline period. Results: The cohort included 498 MM patients treated with carfilzomib; 108 (22%) patients had ≥1 cardiac event identified by both IP and OP claims and 24 (5%) had ≥1 hospitalized cardiac event. Of the 24 hospitalized patients, 14 were hospitalized during carfilzomib treatment (median days to onset = 104) and 8 were hospitalized after carfilzomib treatment (>30 days post dosing; median days to onset = 284). The median age (range) of the 24 patients with hospitalized cardiac events and those with no hospitalized cardiac claims (n=474) was 62 (37, 79) and 61 (36, 96) years, respectively (Table). Baseline medical history of any cardiac event was evident for 92% of hospitalized patients and 84% of non-hospitalized patients. Among hospitalized patients, 25% were over 75 years as compared with 13% of non-hospitalized patients. In univariate analysis, patients with baseline amyloidosis, hypertensive chronic kidney disease, and chronic kidney disease had higher odds of having a hospitalized cardiac event. No significant differences were seen in the proportion of patients with or without a hospitalized cardiac event when evaluated by line of therapy or by carfilzomib treatment regimen (monotherapy or combination). Among patients aged 75+ years, 8.7% were hospitalized, while 2.5% and 4.9% of 65-74 and 18-64 year old patients were hospitalized, respectively (Table). IR per 1000 PYRs [95% CI] among the 14 carfilzomib-treated MM patients hospitalized for any cardiac event during the carfilzomib treatment period was 89.7 (49.0; 150.5) - see Figure for IRs of specific cardiac events. Conclusions: Among carfilzomib-treated patients in a US claims database, hospitalization for a cardiac event was uncommon (~5%) and does not exceed what has been observed in MM patients. Patients at highest risk for cardiac hospitalizations had a history of amyloidosis or chronic renal failure. Additional analyses in much larger populations are needed to better understand risk factors for these events. Disclosures Chari: Array Biopharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Research Funding. Aggarwal:Amgen: Employment, Equity Ownership. Mezzi:Amgen Inc.: Employment, Equity Ownership. Wang:Amgen Inc.: Employment, Equity Ownership. Kim:Amgen Inc.: Employment, Equity Ownership. Zhu:Amgen Inc.: Consultancy. Braunlin:Amgen Inc.: Employment, Equity Ownership. Werther:Amgen Inc.: Employment, Equity Ownership. Mikhael:Abbvie: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Onyx: Research Funding.

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Risk Factors Associated with Earlier Relapse and Death and Treatment Response in Patients with Follicular Lymphoma in Taiwan

Blood ◽

10.1182/blood-2018-99-112347 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5338-5338

Author(s):

Sung-Nan Pei ◽

Kuan-Chih Huang ◽

Ming-Chung Wang ◽

Ching-Yuan Kuo ◽

Ming-Chun Ma ◽

...

Keyword(s):

Risk Factors ◽

Follicular Lymphoma ◽

Disease Stage ◽

Newly Diagnosed ◽

Employment Equity ◽

Factors Associated ◽

Β2 Microglobulin ◽

Tertiary Center ◽

Equity Ownership

Abstract Background: Follicular Lymphoma (FL) has been relatively uncommon in Asia. Information on prognostic risk factors are scarce in the Asian population. We evaluated patients with FL in a tertiary medical center in Taiwan to gain better understanding of real world treatment and risk factors affecting outcome. Purpose: To evaluate clinical outcomes and risk factors associated with outcome in patients with FL in Taiwan. Methods: We conducted a retrospective cohort study using electronic medical records from Kaohsiung Chang Gung Memorial Hospital, a major regional hospital in southern Taiwan, from 01 January 2008 to 31 December 2017. Newly diagnosed patients with FL were enrolled from 01 Jan 2008 to 31 Dec 2013. All eligible patients were followed-up until study end, loss to follow-up or until death, whichever occurred first. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Risk factors of EFS and OS were identified using Cox proportional hazards model. A significant association was set at p<0.01. Results: A total of 67 patients with newly diagnosed FL were included in the cohort analysis, accounting for 13.7% (67/489) patients with B cell non-Hodgkin lymphoma during the enrolment period. Median follow-up time was 60 months. At diagnosis, median age was 58 years (range 28-95), 56.7% (38/67) of patients were female, and 68.7% (46/67) had Stage III-IV disease. There were 37.3% (25/67) of patients with bone marrow involvement and 22.4% (15/67) with involvement of more than one extra-nodal site. The percentage of patients with low, intermediate and high-risk FL was 32.8%, 25.4%, 38.8%, respectively by FLIPI-1, and 13.4%, 44.8%, 26.9% by FLIPI-2. 72% (48/67) of patients received first-line treatment with regimens that included rituximab, cyclophosphamide, vincristine, prednisolone ± doxorubicin. Of these, 54.2% (26/48) of patients demonstrated complete response and 37.5% (18/48) had a partial response. A further 22.4% (15/67) patients received other treatments and 6.0% (4/67) patients did not receive any treatment. Progression of disease within 24 months after commencing treatment occurred in 32.8% of patients. The 5-year EFS and OS for all patients were 48.6% and 76.2%, respectively (Figure). A higher relapse rate was associated with the presence of B symptoms (HR 6.1; 95% confidence interval [CI] 2.8-13.2), ECOG score ≥2 (HR 5.7; 95% CI 1.7-19.6), FLIPI-2 score ≥3 (HR 5.5; 95% CI 1.4-20.6), large cell transformation (HR 4.1; 95% CI 1.66-10.6), elevated β2 microglobulin (HR 4.0; 95% CI 1.8-9.1), age >70 years (HR 3.6; 95% CI 1.7-7.5), involvement of more than one extra-nodal site (HR 3.5; 95% CI 1.6-7.6) and elevated LDH (HR 2.5; 95% CI 1.3-5.1) (Table 2). Conclusion: Most patients with FL in this tertiary center in Taiwan were at an advanced disease stage at diagnosis. While the majority responded to conventional chemotherapy, one-half of patients progressed within 5 years. Involvement of extra-nodal sites, B symptoms, older age (>70) higher FLIPI-2 score, elevated β2 microglobulin and ECOG score ≥2 were identified as risk factors for earlier relapse and death. Disclosures Pei: Janssen Research & Development, LLC: Research Funding. Huang:Janssen Research & Development, LLC: Employment. Rothwell:Janssen Research & Development, LLC: Employment, Equity Ownership. Qiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Liu:Janssen Research & Development, LLC: Employment, Equity Ownership.

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Assessment of Treatment Patterns and Adverse Events Among Patients with Chronic Myeloid Leukemia Using Tyrosine Kinase Inhibitors

Blood ◽

10.1182/blood-2018-99-112695 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3585-3585

Author(s):

Sudeep Karve ◽

Joanna C Huang ◽

Nikhil Ranade ◽

Sanchita Porwal ◽

Monali Desai ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Cardiovascular Events ◽

Kinase Inhibitors ◽

Treatment Patterns ◽

First Line ◽

Employment Equity ◽

Equity Ownership

Abstract INTRODUCTION: Chronic myeloid leukemia (CML), a myeloproliferative neoplasm is primarily treated using tyrosine kinase inhibitors (TKIs). Several next-generation TKIs (dasatinib, nilotinib, bosutinib, ponatinib) have been approved since the first approval of imatinib in 2002. With varying safety profiles, data on non-trial long-term TKI use and associated adverse events (AE) can aid in clinical decision making. Using population based data sources the current study assessed treatment patterns and AEs in a non-trial setting among TKI users with CML. METHODS: A retrospective cohort analysis was conducted using MarketScan Commercial, and Supplemental Medicare databases (2012-2016). Data includes details on medical (e.g., date of diagnosis, diagnosis codes, procedures) and pharmacy (e.g., drug dose, duration, strength) utilization for over 90 million individuals enrolled in employer-sponsored health-plans in the US. Patients with a prescription claim for TKI along with at least 2 medical claims on separate dates with a diagnosis code for CML (ICD-9-CM: 205.10 - 205.12; ICD-10: C92.10-C92.12) were selected. Patients were aged ≥18 years at TKI initiation and had continuous health plan enrollment ≥6 months before and ≥6 months after TKI initiation. Patients were followed from TKI initiation until health plan disenrollment or end of database, whichever occurred earlier (defines follow-up period). TKI treatment patterns including initial dose, initial and total TKI treatment duration, treatment switching and discontinuation were assessed. Frequency and proportion for incident (i.e. newly observed conditions) AEs including rash, bleeding, gastrointestinal disorders (nausea, vomiting, diarrhea), tumor lysis syndrome and cardiovascular events (CHF, arrhythmia, peripheral arterial occlusive disease, cerebrovascular events) and post-AE outcomes (switching, discontinuation, dose reduction) were assessed. AE list was developed based on commonly reported events in clinical trials involving TKIs for CML and clinical judgement. All analyses were descriptive in nature. RESULTS: Study included 2,213 CML patients with mean age (standard deviation [SD]) of 55 (15) years, of which 55% were male and 55% had ≥2 co-morbid conditions. Post CML diagnosis, first-line of TKI initiated was imatinib (41%), dasatinib (36%), nilotinib (22%), and bosutinib and ponatinib (1% each). The average (SD) follow-up duration post TKI initiation was 607 (442) days. Mean (SD) duration of first-line TKI prescription was 392 (383) days. 61% of patients continued initial TKI during the follow-up period, 7% discontinued and 32% switched/re-initiated TKI (Figure 1). 39.2% patients had at least 1 incident AE while on index TKI therapy. GI disorders (20.4%) were the most commonly observed AE, followed by cardiovascular events (14.6%), rash (8.4%), bleeding (8.0%), and TLS (0.2%). The average (SD) time to GI disorders, bleeding, cardiovascular event, rash, and TLS was 242 (274) days, 238 (272) days, 219 (261) days, 222 (255) days, and 223 (285) days, respectively. The rates of discontinuation, treatment switch or dose reduction were largely similar across all AEs (Figure 2). The mean duration on any TKI (all-lines of therapy) was 561 (438) days. The most commonly observed AEs on while of TKI therapy (irrespective of line of therapy) were GI disorders (24.7%), followed by cardiovascular events (17.3%), rash (11.5%), bleeding (10.1%) and TLS (0.5%). CONCLUSIONS: The study helps address the current literature gap of long-term treatment patterns and AE among patients with CML using TKIs in a non-clinical trial setting. During follow-up 46% patients experienced at least 1 incident AE while on TKI therapy. Majority of patients (61%) continued same TKI therapy following AE. The type and rate of AE were similar following first-line therapy and anytime on TKI (any-line) during the follow-up period. Study results may not be comparable to clinical trial findings due to certain limitations; e.g., this study did not capture all adverse events but assessed incident AE based on a pre-specified list. Also, due to limitations of administrative claims data, assessment of AE grade was not feasible. However, findings from this study can complement clinical trial data in selection of TKIs for long-term use in real-world setting and can also be of value in selecting TKIs for future clinical studies involving novel combinations in CML. Disclosures Karve: AbbVie: Employment, Equity Ownership. Huang:ZS Associates: Employment; Novo Nordisk Inc: Equity Ownership; AstraZeneca: Research Funding. Ranade:ZS Associates: Employment. Porwal:ZS Associates: Employment. Desai:AbbVie: Employment, Equity Ownership. Rosenberg:AbbVie: Employment, Equity Ownership.

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Real-World Differences in Characteristics and Survival of Relapsed AML Patients with and without Transplant

Blood ◽

10.1182/blood-2018-99-118621 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2297-2297

Author(s):

Abdalla Aly ◽

Saurabh Ray ◽

Anuj Shah ◽

Marc Botteman

Keyword(s):

Overall Survival ◽

Real World ◽

Research Funding ◽

Cell Transplant ◽

Employment Equity ◽

Risk Of Death ◽

Hazard Ratios ◽

Equity Ownership ◽

To Receive

Abstract Background: Some AML patients, particularly those relapsing rapidly, may not get a chance to receive a potentially curative stem cell transplant (SCT) due to early death, among other reasons. This study compares the differences in characteristics and survival of relapsed AML patients with and without SCT, as observed in a real-world setting. Methods: Relapsed AML patients aged 66-75 years were identified from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database by medical claims associated with ICD-9 code 205.02 (2009-2014). Patients were followed from relapse to the earliest of death, SCT, or end of follow-up. Baseline characteristics were compared between relapsed AML patients with and without SCT. The SCT rates were estimated after adjusting for the competing risk of death. The Fine and Gray method was used to identify predictors of receiving SCT and were reported in terms of sub-distribution hazard ratios (SHR) and 95% confidence intervals (CI). Kaplan-Meier estimates (reported in terms of median and 6-, 12-, and 24-months survival rates, tested with a log Rank test statistic) and a Cox proportional hazards model adjusting for age, sex, race, Census region, marital status, urban location, Charlson comorbidity index (CCI), and diagnosis year (reported in terms of hazard ratios (HR) and 95% CI) was used to assess the difference in survival between patients with and without SCT. Results: Of the 474 relapsed AML patients (median age, 70 years, median follow up, 4.4 months, male, 55%) included in the study, 8% received SCT, 80% died without having SCT and 12% were administratively censored. Patients were less likely to receive SCT if they were 71-75 years old (SHR 0.28, 95% CI (0.19 to 0.41; P <.001) and had higher comorbidity with CCI >3 (SHR 0.16, 95% CI (0.06 to 0.44; P <.001). The median overall survival was 16.1 months for patients with SCT vs. 4.1 months for those without SCT (log rank P <.001; adjusted HR 0.52, 95% CI (047 - 0.57; P <.001)). The 6-, 12-, and 24-month overall survival for all relapsed AML patients was 42%, 26%, and 12%, respectively. For patients with SCT, the 6-, 12-, and 24-month overall survival was 84%, 59%, and 43%, respectively. For patients without SCT, the 6-, 12-, and 24-month overall survival was 39%, 23%, and 12%, respectively. Conclusions: Relapsed AML patients who received SCT experienced significantly longer survival compared to those who did not receive SCT in this elderly study population. However, only 8% of all relapsed AML patients received SCT. Therapies that bridge more patients to SCT are expected to improve overall survival in this high unmet need population. Disclosures Aly: AstraZeneca: Research Funding; Celgene: Research Funding; BMS: Research Funding; Pharmerit International: Employment, Research Funding; Daiichi Sankyo Incorporated: Research Funding. Ray:Daiichi Sankyo Incorporated: Employment, Equity Ownership. Shah:Celgene: Research Funding; Pharmerit International: Employment, Research Funding; Daiichi Sankyo Incorporated: Research Funding; BMS: Research Funding. Botteman:Daiichi Sankyo Incorporated: Research Funding; BMS: Research Funding; Celgene: Research Funding; Pharmerit International: Employment, Equity Ownership, Research Funding; Bioverativ: Consultancy, Other: Provided consulting to Bioverativ, Research Funding.

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Persistence of Ruxolitinib Treatment in Patients with Myelofibrosis at Community Oncology Practices in the United States-Contemporary Data

Blood ◽

10.1182/blood-2019-123833 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5385-5385

Author(s):

Jingbo Yu ◽

Jonathan K. Kish ◽

Dilan Paranagama ◽

Philomena Colucci

Keyword(s):

United States ◽

High Risk ◽

Chart Review ◽

The United States ◽

Current Analysis ◽

First Line ◽

Employment Equity ◽

Persistence Rates ◽

Equity Ownership

Introduction Myelofibrosis (MF) is a chronic myeloproliferative neoplasm frequently associated with debilitating disease-related symptoms and shortened overall survival (OS). Ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, was approved on November 16, 2011 for patients with intermediate- and high-risk MF. The phase 3 COMFORT trials demonstrated that ruxolitinib reduced spleen volume, improved MF-related symptoms, and prolonged OS. In the COMFORT trials, the median duration of ruxolitinib treatment was 2.8 years (5-year pooled analysis). The objective of this real-world chart review study is to describe persistence of ruxolitinib treatment early on in the treatment course in patients with MF at community hematology/oncology practices in the United States. Methods Medical charts from community hematology/oncology practices in Cardinal Health Oncology Provider Extended Network (OPEN) were reviewed and abstracted into electronic case report forms by physicians. Physicans were instructed to abstract data from the earliest eligible patients and then chronologically, thereafter. This analysis included adult patients diagnosed with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF between 01/2012 and 12/2016. Patients were required to have intermediate- or high-risk MF (based on a data-derived International Prognostic Scoring System [IPSS] risk categorization), have platelet count >50 × 109/L at the time of diagnosis, have received ruxolitinib as first-line treatment, and have ≥6 months of follow up after the initiation of ruxolitinib; patients who died within 6 months of initiation of ruxolitinib were considered as discontinued patients and were included in the analysis. Three- and 6-month persistence rates are reported. Results A total of 141 patients from 22 community hematology/oncology practices were included in the analysis; 3 patients who were still on ruxolitinib at the end of the study period, but with less than 6 months of follow up, were excluded from the analysis. Mean (SD) age at diagnosis was 69.8 (10.2) years, 61.7% were male, 71.6% had primary MF, and 56.7% were high-risk at diagnosis. Median time from diagnosis to ruxolitinib initiation was 36 (interquartile range [IQR], 20-91) days. The majority of patients initiated ruxolitinib in 2016 or later (Figure). The starting dose of ruxolitinib was 5 mg twice daily [BID] in 7.8%, 10 mg BID in 9.9%, 15 mg BID in 39.7%, 20 mg BID in 34.8%, and 25 mg BID in 7.8%. Three- and 6-month persistence rates were 97.2% and 91.5%, respectively (Table). Discussion A previous retrospective chart review of prescription claims and patient level data evaluated a cohort of patients with MF prescribed ruxolitinib just prior to and shortly after its approval (November 1, 2011 to August 31, 2012); in that study, 3- and 6-month persistence rates of 39.1% and 27.0%, respectively, were reported (Blood. 2013[122]:2833). In the current study, the 3- and 6-month persistence rates were notably higher at 97.2% and 91.5%, respectively. These higher rates are likely attributable to a number of factors. The current analysis was limited to patients treated first-line with ruxolitinib. Furthermore, the index period in the current analysis extended almost 5 years beyond ruxolitinib approval; in this 5-year period, there were a number of publications in support of ruxolitinib dose optimization with particular focus on the first 8-12 weeks of treatment (J Hematol Oncol. 2013[6]:79; Int J Hematol. 2016[104]4:420-9). The 3- and 6-month persistence rates reported here demonstrate that only a small proportion of patients with myelofibrosis treated with first-line ruxolitinib discontinued the drug early on in their treatment course. Conclusion This contemporary analysis demonstrates high rates of 3- and 6-month persistence of first-line ruxolitinib in patients with MF treated in community practices. Proper monitoring and management of the expected mechanism-based toxicity of a JAK inhibitor and proper dose titration for insufficient response, early in the treatment course, may help patients derive maximum, long-term benefits from ruxolitinib. Disclosures Yu: Incyte: Employment, Equity Ownership. Kish:Cardinal Health: Employment. Paranagama:Incyte: Employment, Equity Ownership. Colucci:Incyte: Employment, Equity Ownership.

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Characterizing a Population with Severe Manifestations of Sickle Cell Disease Using U.S. Real-World Evidence

Blood ◽

10.1182/blood-2018-99-118874 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4811-4811

Author(s):

Clark Paramore ◽

Amanda Kong ◽

Sachiyo Minegishi ◽

Weiliang Shi

Keyword(s):

Sickle Cell ◽

Real World ◽

Clinical Manifestations ◽

Early Mortality ◽

Cell Disease ◽

Employment Equity ◽

Real World Evidence ◽

History Of ◽

Equity Ownership

Abstract Background Sickle cell disease (SCD) is a monogenetic disorder, with 300,000 to 400,000 infants born annually with the disease around the world (Kato et al, Nat Rev Dis Primers 2018). SCD is a progressively debilitating and life-threatening disease characterized by hemolytic anemia, painful vaso-occlusive events (VOEs) and persistent vasculopathy that result in significant morbidity, poor quality of life and early mortality. There is significant heterogeneity in clinical manifestations of SCD, given that vaso-occlusion and hemolysis-associated endothelial dysfunction may manifest in any tissue or organ. Severely affected patients may experience a diverse set of complications (Kato et al, Nat Rev Dis Primers 2018). Given the limited research to date in this area, the objectives of this real-world, retrospective study were to 1) identify and describe severely debilitating clinical complications experienced by patients with SCD in the U.S. and 2) examine rates of associated co-morbidities for this cohort. Methods A retrospective cohort analysis was undertaken utilizing patient-level, de-identified administrative claims data from the Truven Health U.S. MarketScan® Commercial, Medicare Supplemental, and Medicaid Multi-State Databases, for the period from January 1, 2010 to September 30, 2016. SCD patients were identified based on: ≥ 2 separate dates during study period with a medical claim having a SCD diagnosis (based on set of relevant ICD-9 or ICD-10 CM codes) and included in analyses if they had ≥ 2 years of follow-up with continuous plan enrollment. Treatment approaches and clinical outcomes were defined using a pre-specified list of relevant diagnosis and treatment codes. Commonly identified characteristics of severe SCD were assessed for each patient during their 1st 2 years of continuous enrollment during study period. These included 1): having frequent (i.e. ≥ 4) VOEs [i.e. sickle cell crises either distinct from acute chest syndrome (ACS) or unspecified] that require emergency room care or hospitalization, 2) stroke or history of stroke, 3) receiving chronic red blood cell (RBC) transfusions, or 4) ≥ 1 medical encounters for ACS. Results A total of 18,740 patients with SCD (56% Female; 61% from Medicaid database; 75% Black [only reported in Medicaid sample]) met the study criteria. Nearly 60% of the cohort were < 20 years old, 73% < 30 years old and only 9% ≥ 50 years old. Over the 2-year follow-up period, 23% of patients had ≥ 1 prescription for hydroxyurea. Table 1 provides a breakdown of patient comorbidities by age group. The most common comorbidities across all evaluated patients were cardiomegaly (12.6%), depression (11.8%), anxiety (7.8%) and osteonecrosis (7.7%). The prevalence of chronic kidney disease (CKD) increased most markedly as patient age increased, with 20% of 55-64-year-olds experiencing CKD. By the age of 35, over half (53.3%) of the SCD patients had at least one of the 13 listed comorbidities; this increased to 74.2% for a subset with 4 years of follow-up available. Thirty-three percent of patients had ≥ 1 inpatient admission for a VOE. Figure 1 shows patient counts for the selected complications of severe SCD, with rates and overlap among subgroups varying between children and adults. Approximately one-third of patients with SCD with multiple hospitalizations/emergency visits due to VOEs also had an ACS event. There was limited overlap in patients with SCD with history of stroke and those with an ACS event; and as expected there was very little overlap in patients with SCD receiving chronic transfusions and those with ≥4 VOEs or those with ACS (as RBC transfusions are prescribed to certain SCD patients to limit symptom impact). Conclusions Based on this contemporary real-world evidence from the U.S. setting, a substantial proportion of patients with SCD experience a diverse set of severely debilitating complications of the disease, as well as other co-morbidities associated with the disease. The high rate of comorbidities across all age groups and overrepresentation of patients younger than 30 years of age (relative to age distribution of general U.S. population) indicate that patients with SCD still experience significant morbidity and early mortality with current standard medical care. Given the notable heterogeneity of the clinical manifestations of SCD, future treatment approaches should address the root cause of the disease. Disclosures Paramore: bluebird bio: Employment, Equity Ownership. Kong:bluebird bio: Consultancy, Research Funding. Minegishi:bluebird bio: Employment, Equity Ownership. Shi:bluebird bio: Employment, Equity Ownership.

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Trends in the Multiple Myeloma Treatment Landscape: A United States Analysis of Oscer Electronic Health Record Data 2011-2019

Blood ◽

10.1182/blood-2019-125972 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4722-4722

Author(s):

Megan Braunlin ◽

Rajesh Belani ◽

Jacqueline Buchanan ◽

John Travis Wheeling ◽

Christopher Kim

Keyword(s):

Multiple Myeloma ◽

Second Line ◽

Front Line ◽

First Line ◽

Electronic Health Record Data ◽

Employment Equity ◽

The Us ◽

Equity Ownership ◽

Electronic Health

Introduction The treatment (tmt) for multiple myeloma (MM) is evolving with the introduction of novel immunomodulatory drugs (IMiD), monoclonal antibodies (MoAB), and proteasome inhibitors (PI). As new efficacious therapies are approved, the prevalence of MM continues to increase and remains an incurable disease. There is limited real-world evidence describing these temporal changes (Song 2016, Curr Med Res Opin; Fonseca 2017, Leukemia). This study characterizes trends in MM tmts and patient (pt) survival from 2011-19 in the US-based Flatiron electronic health records (EHR) database. Methods Data analyzed were from an enhanced database of oncology EHR contained in the Oncology Services Comprehensive Electronic Records (OSCER), generated by Flatiron Health that includes additional unstructured data processing (New York, NY, March 31, 2019). OSCER represents a longitudinal, demographically and geographically diverse database with data from over 265 cancer clinics representing over 2 million active pts treated at primarily community-based hematology/oncology practices in the US. Inclusion criteria included adult pts ≥18 years (yrs) with a diagnosis of MM (ICD9: 203.x; ICD-10: C90.x) and at least two clinic visits after 2011. Pt and disease characteristics were characterized; line of therapy (LOT) (1-5), year of therapy initiation, and all tmt regimens received. Follow-up time was measured from tmt index until death or last follow-up. Kaplan-Meier overall survival (OS) proportions were estimated from LOT tmt index. Results A total of 9289 pts were identified. At diagnosis the median age was 69 yrs, with 54% of pts male and 68% white. The majority of pts were treated in the community setting (89%) and 11.5% presented with high risk cytogenetics (del17p, t(4;14), t(14;16)). International Staging System (ISS) data was available in 49.2% of subjects, with 16.6%, 16.1% and 16.3% stage 1, 2, and 3 respectively. Among the 91% of pts who received tmt for newly diagnosed MM, median time to tmt was 30 days. In 2017-18, triplet combination (comb) PI-IMiD-dexamethasone (dex) was the most common front (48%) and second line regimen (27%); and the use of this comb increased in both first and second lines over the study period. In contrast, the use of IMiD or PI -dex doublet regimens decreased. In third line setting, PI-IMiD-dex remained the most common comb in 2017-18 (21%) but gradually decreased over the study period with a dip in 2013-14 while MoAB-IMiD-dex combs increased from 3% to 12% (2015/16-2017/18). In second, third, and fourth line MoAB-IMiD-dex comb increased to 8%, 12%, and 14% respectively beginning in 2015 (Table 1). MM tmt regimens changed over the study period, most notably in the first and second LOTs. By 2017-18, triplets replaced doublets as the most common front line (58%) and second line (45%) therapies over the study period. Across all LOTs, triplets were the most prescribed comb in 2017-18 with 42%, 42% and 30% in third, fourth, and fifth lines. Over the study period, monotherapies decreased to 12% in frontline, but their use has remained constant in later lines (Table 2). Overall, 26% of pts received a transplant during follow-up. Approximately 34% of pts survived until the end of follow-up. With each LOT, OS deceased. Median OS of pts treated in first line was 57 months and decreased to 44 months, 32 months, and 25 months in second, third, and fourth lines respectively (Figure 1). OS of MM pts who received first line tmt appears to increase the more recently they were diagnosed. Median OS of MM pts diagnosed in 2013-14 was slightly longer compared to pts diagnosed in earlier yrs (2011-12); 60 months compared to 56 months. Median OS was not reached in 2015-16 (Figure 2). Conclusion Triplet therapies have replaced doublet therapies over time as more options became available to MM pts, especially in frontline setting; frontline monotherapies have nearly halved since the beginning of the study period. In 2015, tmt patterns begin to shift as MoAB based triplets were approved and comprised a higher proportion of the regimens in the relapsed and refractory population. Yet, the majority of pts are still receiving PI-IMiD-dex triplets. OS estimates suggest survival in front line treated pts is slowly increasing in recent yrs. These data illustrate the current tmt landscape of MM and the changes that have occurred since the introduction of novel therapies over the past 8 yrs. MM disease management continues to evolve. Disclosures Braunlin: Amgen, Inc.: Employment. Belani:Amgen, Inc: Employment, Equity Ownership. Buchanan:Amgen Inc.: Employment, Other: Owns Amgen stock, Research Funding. Kim:Amgen, Inc.: Employment, Equity Ownership.

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