Real World Assessment of Treatment Patterns and Outcomes Among Multiple Myeloma Patients across Different Risk Stratification Criteria in the United States: A Retrospective Cohort Study

Abstract Background: Despite the development of highly active novel agents, high risk (HR) multiple myeloma (MM) patients continue to demonstrate relatively poor prognosis. Limited data is published on how treatment patterns with risk stratification systems have changed over time. Moreover, real world studies using electronic health records (EHRs) have not evaluated the performance of risk stratification systems with real world outcomes. This study aims to evaluate the ability to implement three different risk stratification systems - international staging system (ISS), revised ISS (R-ISS), and high-risk chromosomal abnormalities (HRCA, defined as presence of del(17)p, t(4;14) and/or t(4;16)) [Palumbo et al. 2015] - to characterize treatment patterns and associated outcomes [real world overall survival (rwOS) and real world progression free survival (rwPFS)] among newly diagnosed MM (NDMM) patients in the US community practice. Methods: This study used Flatiron Enhanced MM EHR de-identified database (New York, NY). Newly diagnosed MM patients (≥ 18 years) were diagnosed from January 2015 through June 2020 (cohort 1 - for studying treatment distribution) with follow-up through December 2020, and from January 2015 through December 2018 (cohort 2 - for rwOS and rwPFS), with follow-up through December 2020. Patients with malignancies other than MM were excluded. Proportion of rwOS was measured from treatment initiation until death, and median rwPFS was measured from treatment initiation until death, progression, or start of new line of therapy using Kaplan-Meier method. Results: A total of 1,979 and 1,382 patients were eligible in cohorts 1 and 2, respectively. In both the cohorts, approximately 18% (cohort 1: N=367, cohort 2: N=248), 41% (cohort 1: N=805, cohort 2: N=566), and 37% (cohort 1: N=738, cohort 2: N=508) were HR patients according to the R-ISS, ISS, and HRCA criteria, respectively. Approximately half of the HR patients were ≥70 years old (52% for R-ISS III and ISS III, and 47% for HRCA), with chronic kidney disease stage ≥3 by eGFR for 54% R-ISS III and ISS III, and 34% high risk CA, and ECOG score ≥2 for 18% R-ISS III, 19% ISS III, and 14% HRCA patients. Triplets were the most frequent treatment regimens (62% for R-ISS III and II, and 66% for R-ISS I; 59% for ISS III, and 65% for ISS II and I; 65% for HRCA and 61% for standard risk CA(SRCA) with proteasome inhibitors (PIs) / immunomodulatory agents (IMiDs) / dexamethasone being most common regimen across all the risk stratification criteria. Quadruplet agent use was higher in R-ISS III and ISS III categories (6.8% vs. 3.3% for R-ISS III vs. I; 6.3% vs. 2.8% for ISS III vs. I). The median rwPFS in HR patients were shorter than the lower risk subgroups (R-ISS III: 8.8 months [95% CI 7.1 - 11.0], R-ISS II: 12.1 months [95% CI 10.7 - 13.6], R-ISS I: 23.5 months [95% CI 13.8 - .]; ISS III: 10.4 months [95% CI 8.5 - 11.5], ISS II: 12.7 months [95% CI 10.7 - 14.3], ISS I: 16 months [95% CI 12.2 - 19.5]; HRCA: 10.1 months [95% CI 8.8 - 12.1], SRCA: 13.1 months [95% CI 11.3 - 14.8]). The 2-year rwOS was lower in the HR subgroups (R-ISS III: 0.65 [95% CI 0.59 - 0.70], R-ISS II: 0.79 [95% CI 0.76 - 0.81], R-ISS I: 0.91 [95% CI 0.85 - 0.95]; ISS III: 0.68 [95% CI 0.64 - 0.72], ISS II: 0.81 [95% CI 0.77 - 0.84], ISS I: 0.89 [95% CI 0.85 - 0.92]; HRCA: 0.75 [95% CI 0.71 - 0.79], SRCA: 0.79 [95% CI 0.76 - 0.81]). Discussion: This study found that median rwPFS and 2-year rwOS proportions were consistently lower among HR patients compared to the standard risk individuals. The majority of the HR patients were older, with decreased levels of physical functioning and worse indicators of end-organ damage including renal function, anemia, and hypercalcemia. Most patients received triplets with frequent use of PIs likely for aggressive disease control among HR patients. Some HR patients received more quads than lower risk patients suggesting treatment intensification, but HR patients also received stem cell transplants at a lower rate. Although a smaller proportion of patients have all the data collected needed for R-ISS classification, the consistent findings across treatment outcomes suggest that R-ISS is implementable in real world studies and has a greater discriminatory ability than ISS or HRCA alone. Overall, this study suggests that HR patients have relatively poor outcomes which calls for the study of risk-adapted implementation of novel therapies among this patient population in the US community practice settings. Figure 1 Figure 1. Disclosures Rahman: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company. Kim: Amgen: Current Employment, Current equity holder in publicly-traded company. Mateus: Amgen Inc.: Current Employment, Other: Work at Amgen as a contract employee through DOCS. Keegan: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company.

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Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽

10.1182/blood.v112.11.95.95 ◽

2008 ◽

Vol 112 (11) ◽

pp. 95-95 ◽

Cited By ~ 1

Author(s):

Prashant Kapoor ◽

Shaji Kumar ◽

Rafael Fonseca ◽

Martha Q. Lacy ◽

Thomas E Witzig ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

Plasma Cell ◽

Risk Groups ◽

Newly Diagnosed ◽

High Risk Patients ◽

Risk Patients ◽

The Impact ◽

Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

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Treatment Patterns and Outcomes of 1205 Patients on Novel Agents in the US Veterans Health Administration (VHA) System: Results from the Largest Retrospective EMR and Chart Review Study in the Real-World Setting

Blood ◽

10.1182/blood-2019-122434 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 795-795

Author(s):

Christopher R Frei ◽

Hannah Le ◽

Daniel McHugh ◽

Cynthia Elesinmogun ◽

Samantha Galley ◽

...

Keyword(s):

Dose Reduction ◽

Real World ◽

Chart Review ◽

Treatment Initiation ◽

Treatment Patterns ◽

Novel Agents ◽

Major Bleed ◽

The Us ◽

Review Study

Introduction : CLL is the most common chronic leukemia in the US, with nearly 20,000 new cases expected annually. Novel agents, such as ibrutinib, idelalisib, and venetoclax, have been approved in recent years and provide oral options for CLL. However, there is limited data regarding real-world treatment patterns with these novel agents. This study describes dose reduction and discontinuation rates, reasons for both, and outcomes, including overall survival (OS) and duration of therapy (DOT), in CLL patients treated with novel agents. Methods : This is an analysis of a large retrospective cohort study of adult patients (≥ 18 years old) with CLL, treated with novel agents in the VHA from 10/01/2013 to 3/31/2018. Historical data were examined for up to 20 years prior to the enrollment period (10/01/1993 to 9/30/2013). Index date was defined as the date of novel agent initiation. The follow-up period was a minimum of 6 months post index date. Variables, collected via a structured EMR database, included patient demographics, and clinical and treatment characteristics. CLL diagnosis, molecular profiles, and reasons for dose reduction and discontinuation were abstracted by chart review. Descriptive statistics were used to summarize baseline characteristics, treatment patterns, and outcomes. Results: A total of 1205 CLL patients were included in this analysis. Of these, in first observed line, 328 (27%) patients received ibrutinib; in relapsed/refractory observed line (r/r), 741(62%) patients received ibrutinib, 49 (4%) patients on idelalisib, and 87 (7%) patients on venetoclax. Ibrutinib patients in first observed line had a median (range) age of 73 (48-96) years and a median follow-up of 23 (3-54) months after treatment initiation. Dose reduction (n=83, 25%) and discontinuation (n=108, 33%) were frequently due to adverse events (AEs) (93% and 64%). Median DOT to ibrutinib discontinuation was 8 months. The most common AEs leading to dose reduction were major bleed (15%) and rash (15%). The most common AEs leading to discontinuation were atrial fibrillation (20%), major bleed (19%), and infection (11%). The calculated median OS from initiation was 31 (14-49) months. R/R ibrutinib patients had a median age of 72 (45-96) years and had 31 (2-85) months of follow-up after treatment initiation. Dose reduction (n=242, 33%) and discontinuation (n=263, 35%) were frequently due to AEs (89% and 63%). Median DOT to ibrutinib discontinuation was 12 months. The most common AEs leading to dose reduction were thrombocytopenia (13%), arthralgia/myalgia (13%), and infection (12%). The most common AEs leading to discontinuation were atrial fibrillation (19%), infection (15%), and major bleed (11%). the calculated median OS from initiation was 39 (9-57) months. R/R idelalisib patients (n=49) had a median age of 72 (55-93) years and had 27 (3-53) months of follow-up after treatment initiation. Dose reduction (n=8, 16%) and discontinuation (n=41, 84%) were frequently due to AEs (100% and 54%). Median DOT to idelalisib discontinuation was 5 months. The most common AE leading to dose reduction was neutropenia (50%). The most common AEs leading to discontinuation were infection (27%) and pneumonia (18%). R/R venetoclax patients (n=87) had a median age of 72 (47-90) years and had 9 (0-35) months of follow-up after treatment initiation. Dose reduction (n=24, 28%) and discontinuation (n=27, 31%) were frequently due to AEs (100% and 41%). Median DOT to venetoclax discontinuation was 5 months. The most common AEs leading to dose reduction were neutropenia (27%) and thrombocytopenia (27%). The most common AEs leading to discontinuation were neutropenia (36%), thrombocytopenia (18%), and infection (18%). There was not enough follow-up time to have a meaningful OS in this cohort. Conclusions: To our knowledge, this is the largest EMR/chart review study among CLL patients initiating treatments in the real-world setting. This study provides evidence regarding patient characteristics, treatment patterns, and outcomes among patients initiating novel agents for the treatment of CLL in the national VHA population. Dose reduction and discontinuation were frequent across all novel agents, with AEs as the most common reason. These data highlight the significant difference in real world data compared with clinical trial data and indicate the unmet need for more tolerable treatment options for CLL patients. Disclosures Frei: AstraZeneca: Research Funding. Le:AstraZeneca: Employment, Other: Stocks. McHugh:AstraZeneca: Employment. Elesinmogun:AstraZeneca: Employment, Equity Ownership. Obodozie-Ofoegbu:UT Austin: Employment.

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Real-World Use of Maintenance Therapy and Associated Outcomes Following Autologous Stem Cell Transplant in US Patients with Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2020-139882 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 25-26

Author(s):

Eric M. Ammann ◽

Annette Lam ◽

Wenze Tang ◽

Tobias Kampfenkel ◽

Mohit Sharma ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Maintenance Therapy ◽

Clinical Outcomes ◽

Real World ◽

Treatment Patterns ◽

Cell Transplant ◽

Newly Diagnosed ◽

The Us

Background: In patients with newly-diagnosed multiple myeloma (NDMM) who receive frontline autologous stem cell transplantation (ASCT), maintenance therapy (MT) following ASCT has been shown to delay disease progression and death. Current National Comprehensive Cancer Network (NCCN) guidelines also recommend MT for patients with MM, including the use of lenalidomide, bortezomib-based regimens, or ixazomib. However, there is limited evidence on the use and outcomes associated with MT in contemporary real-world patients. The present study assessed MT treatment patterns and clinical outcomes in a real-world US cohort of patients with NDMM following ASCT. Methods: This retrospective, observational cohort study included NDMM patients initially diagnosed from 2011-2018 who received frontline ASCT. Patients were selected from the US Flatiron Health (FH) deidentified electronic health record (EHR)-derived database, which includes longitudinal patient-level data from over 265 community-based and academic cancer clinics across the US. To ensure capture of post-ASCT consolidation and MT, the study sample was restricted to patients who resumed contact within the FH network within 60 days following ASCT. Patients were excluded if they received treatment within the context of a clinical trial or had a second transplant within 180 days of their initial ASCT. Patients were classified as receiving MT if (during the 180-day post-transplant period) they initiated treatment with an NCCN-recommended MT regimen or continued to receive a subset of the antimyeloma agents used as induction regimen following ASCT and consolidation (if any). Key measures included baseline demographic and clinical characteristics, antimyeloma treatments (frontline induction, consolidation, and MT, if any), and clinical outcomes (time to next myeloma treatment [TTNT] and overall survival [OS]). Treatment duration and clinical outcomes were analyzed using Kaplan-Meier estimators and Cox regression to account for right-censoring. For TTNT and OS, follow-up began on the earlier of the ASCT date + 90 days or start of MT and continued through the dataset cut-off date (May 30, 2020) or loss to follow-up; TTNT and OS were estimated for patients receiving lenalidomide maintenance [R-MT], bortezomib maintenance [V-MT], or no MT, but was not estimated for other MT regimens due to sample size considerations. Results: 528 NDMM patients (median age 61 years, interquartile range [IQR]: 55, 68; 45.3% female) underwent ASCT and met study inclusion criteria. The most common induction regimens were bortezomib-lenalidomide-dexamethasone (VRd; 60.0%), lenalidomide-dexamethasone (Rd; 16.3%), and cyclophosphamide-bortezomib-dexamethasone (CyBorD; 10.2%). Following ASCT, 7.2% of patients received consolidation therapy and 74.2% received MT (lenalidomide monotherapy [R-MT]: 58.7%; bortezomib monotherapy [V-MT]: 7.6%; other MT: 7.8%). Median duration of MT was 18.0 months (IQR: 8.7, 29.1), and was similar for R-MT and V-MT (median 18.9 and 18.6 months, respectively). MT use increased from 69.3% to 79.0% from 2011-2013 to 2017-2018 (P=0.04); in addition, patients were more likely to have received VRd as induction across different MT (Table 1). R-MT and V-MT were both associated with longer TTNT relative to no MT (unadjusted hazard ratios [HRs]: 0.29 [95% CI: 0.22, 0.38] and 0.39 [95% CI: 0.25, 0.61], respectively) (Figure 1A). Improvements in OS were marginally significant with R-MT (HR: 0.58 [95% CI: 0.33, 1.00]) and nonsignificant with V-MT (HR: 0.86 [95% CI: 0.35, 2.11]) relative to no MT (Figure 1B); however, the OS estimates are characterized by low precision due to the relatively small number of events observed. Limitations included lack of documentation of reasons for treatment in the FH database, and use of consolidation and MT were inferred from observed treatment patterns; therefore, misclassification of MT was possible. Conclusions: This analysis demonstrates that MT use following ASCT has increased in routine clinical practice in the US since 2011-2013, with R-MT being the most common regimen followed by V-MT. However, a substantial proportion of patients did not receive MT. MT use in real-world settings was associated with longer TTNT and a trend toward longer OS. Exploration of additional maintenance regimens to improve clinical outcomes is warranted in this patient population. Disclosures Ammann: Janssen Scientific Affairs: Current Employment, Current equity holder in publicly-traded company. Lam:Janssen: Current Employment. Tang:Janssen: Current Employment. Kampfenkel:Janssen: Current Employment. Sharma:Mu Sigma: Current Employment; Janssen: Other: Contractor. Lee:Janssen: Current Employment. Kaila:Janssen Scientific Affairs: Current Employment. Fu:Janssen: Current Employment. Gray:Janssen: Current Employment. He:Janssen: Current Employment.

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Treatment Patterns and Outcomes Among Patients with Relapsed/Refractory Follicular Lymphoma Treated in Routine Clinical Practice in the US with Three or More Lines of Therapy

Blood ◽

10.1182/blood-2021-145412 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4080-4080

Author(s):

Jamie T. Ta ◽

Stella Arndorfer ◽

Cristina Julian ◽

Mei Wu ◽

Dominic Lai ◽

...

Keyword(s):

Follicular Lymphoma ◽

Real World ◽

Treatment Initiation ◽

Treatment Patterns ◽

Publicly Traded ◽

The Past ◽

Community Oncology ◽

The Us ◽

Early Progression

Abstract Background: Follicular lymphoma (FL) is an indolent, yet incurable disease, and patients often require several lines of therapy throughout their lifetime (Batlevi et al. Blood Cancer J 2020); however, there are limited real-world data available regarding the treatment of a contemporary cohort of patients with relapsed/refractory (R/R) FL. The objective of this study was to assess real-world treatment patterns and outcomes among patients receiving third- and later-line (3L+) therapies for FL in the US. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. During the study period, de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. We selected patients aged ≥18 years with an initial FL diagnosis between January 2011 and January 2021, who had received at least 3 lines of therapy for FL (follow-up ended March 2021). Exclusion criteria included: evidence of clinical trial participation during the study period, high-grade (3b) FL at diagnosis, transformation to an aggressive lymphoma any time before 3L FL treatment, or other anticancer therapies or stem cell transplant 12 months before first-line (1L) FL treatment. Patient demographic and clinical characteristics were assessed using descriptive statistics. Treatment patterns and time to next anti-lymphoma treatment or death (TTNTD) were reported. Median TTNTD was estimated using Kaplan-Meier methods. Results: Of 2,990 patients receiving treatment for FL during the study period, 157 patients who received at least 3 lines of therapy for FL were included. Median age at time of 3L FL treatment initiation was 70 years, and 48.4% (n=76) of patients were male. At initial FL diagnosis, 79.6% (n=125) had low-grade (1-2) FL, 78.3% (n=123) had advanced stage (III/IV) FL, and 68.6% (n=48) of the 70 patients with available Follicular Lymphoma International Prognostic Index (FLIPI) scores had high-risk FLIPI (≥3). Overall, 68.2% of patients had evidence suggestive of early progression of disease within 24 months of 1L FL treatment. The majority of patients were treated at community oncology practices (n=140 [89.2%]). Median time to 3L treatment initiation from diagnosis was 35.6 months, and median follow-up after 3L treatment was 15.4 months. Fifty-two (33.1%) patients received a subsequent fourth-line therapy. The most common 3L treatment regimens received were rituximab (R) monotherapy (n=32 [20.4%]), R plus bendamustine (n=26 [16.6%]), R plus lenalidomide (n=18 [11.5%]), obinutuzumab monotherapy (n=14 [8.9%]), and idelalisib (n=13 [8.3%]; Table). Median TTNTD after 3L treatment was 14.1 months (95% confidence interval: 10-23.6; Figure). Conclusions: Our study provides an update on the heterogeneous treatment landscape for R/R FL in the US for patients receiving 3L+ therapy in real-world clinical practice, the majority of whom were treated in community oncology practices. Many patients requiring 3L+ FL treatment had clinical characteristics predictive of poor prognosis, as evidenced by the high proportion of patients who had evidence of early progression and high-risk FLIPI at diagnosis. Treatment outcomes following 3L therapy remain poor, and approximately one-third of patients required additional treatment beyond 3L. Limitations of this analysis include those inherent to real-world observational databases and the relatively short follow-up of patients with indolent FL in the Flatiron Health database, particularly following 3L FL treatment. Future studies with additional follow-up are warranted. Nevertheless, these findings highlight the ongoing unmet need for novel, effective treatments in this setting in order to improve patient outcomes. Figure 1 Figure 1. Disclosures Ta: Genentech, Inc.: Current Employment. Arndorfer: Genesis Research: Consultancy, Current Employment. Julian: Genentech, Inc.: Current Employment, Current holder of stock options in a privately-held company. Wu: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Lai: Bristol-Myers Squibb: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Shapouri: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment.

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Treatment Patterns, Adverse Events, and Economic Burden in a Privately Insured Population of Newly Diagnosed Patients with Chronic Lymphocytic Leukemia in the United States

Blood ◽

10.1182/blood-2018-99-114735 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3557-3557 ◽

Cited By ~ 1

Author(s):

Shaum Kabadi ◽

Ravi K Goyal ◽

Saurabh P Nagar ◽

James A Kaye ◽

Keith L Davis ◽

...

Keyword(s):

Health Care ◽

Adverse Events ◽

Systemic Therapy ◽

Research Funding ◽

The United States ◽

Treatment Patterns ◽

Newly Diagnosed ◽

The Us ◽

Privately Insured

Abstract Introduction: Contemporary data describing treatment patterns, adverse events (AEs) and outcomes in CLL patients in clinical practice is lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health care resource use (HCRU), and costs in patients with newly diagnosed CLL. Methods: Using a nationally representative population of privately insured patients in the US, adult patients with CLL were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL-directed treatment. Treatment patterns up to 4 lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per-patient monthly HCRU and costs were assessed overall and by number of unique AEs. Results: Of all patients meeting the selection criteria (n=7,639; median age, 66 years), 18% (n=1,379) received a systemic therapy during study follow-up. The most common systemic therapy regimens, regardless of therapy line, were bendamustine/rituximab (BR) (32%), rituximab monotherapy (24% [including maintenance]), ibrutinib monotherapy (15%), and fludarabine/cyclophosphamide/ rituximab (FCR) (14%). Of these, BR was the most common LOT-1 regimen (28.1%), while ibrutinib was the most common regimen in LOT-2 (20.8%) and in LOT-3 (25.5%). Use of idelalisib was limited to 1.6% of all patients receiving systemic therapy; however, an increasing trend was observed as patients moved from first to fourth LOT (<1% in LOT-1, 3.1% in LOT-2, 4.7% in LOT-3, and 8.6% in LOT-4). AEs identified during the most common treatments for CLL are presented by treatment regimen in Table 1. The mean monthly all-cause and CLL-related costs, among patients treated with a systemic therapy, were $7,943 (SD=$15,757) and $5,185 (SD=$9,935), respectively. Figure 1 depicts mean monthly costs by care setting and number of AEs, among all patients. Mean (SD) monthly all-cause costs during the post-index date follow-up were $905 ($1,865) among those with no AEs, $1,655 ($5,364) among those with 1-2 AEs, $2,883 ($8,483) among those with 3-5 AEs, and $6,032 ($13,290) among those with ≥6 AEs. Conclusions: This population-based study yielded recent real-world evidence on treatment patterns, AEs, HCRU, and costs in patients enrolled in health plans in the US. Immunochemotherapy, particularly BR, remained the preferred frontline therapy for CLL, whereas ibrutinib was the preferred therapy in LOT-2 and LOT-3, during the study period. This study demonstrates that the AE burden associated with current treatment alternatives for CLL is substantial, and the management of AEs occurring during treatments may have a significant impact on the overall health care costs. Disclosures Kabadi: AstraZeneca: Employment. Goyal:RTI Health Solutions: Employment, Research Funding. Nagar:RTI Health Solutions: Employment, Research Funding. Kaye:RTI Health Solutions: Employment, Research Funding. Davis:RTI Health Solutions: Employment, Research Funding. Mato:Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Sunesis: Honoraria, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Honoraria; Acerta: Research Funding; Prime Oncology: Speakers Bureau; Regeneron: Research Funding.

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Significance of Modified Risk Stratification Msmart 3.0 and Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2019-130092 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5593-5593

Author(s):

Andrey Garifullin ◽

Sergei Voloshin ◽

Vasily Shuvaev ◽

Irina Martynkevich ◽

Elizaveta Kleina ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Risk Stratification ◽

Risk Group ◽

High Risk Group ◽

Prognostic Impact ◽

Newly Diagnosed ◽

Genetic Abnormalities ◽

Standard Risk

Background The risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies and other factors. The most extensive and modern system in this time is mSMART risk stratification involving many parameters such as genetic anomalies, albumin, beta-2-microglobulin, LDH, Plasma Cell S-phase and GEP levels. It is possible to use risk-adapted treatment programs with or without ASCT. Nevertheless, the role of complex karyotype, combination of genetic abnormalities and ASCT remains unclear. Aims To estimate the genetic abnormalities in patients with newly diagnosed multiple myeloma and define the role of risk-stratification and ASCT in prognosis of disease. Methods The study included 159 patients (median age 63 years, range 28 - 83; male: female ratio - 1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). ASCT was performed at 42% patients. Results The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) - 16.3% (26/159), t(4;14) - 5.0% (8/159); TP53/del17p - 5.6% (9/159); 1p32/1q21 amp/del - 12% (19/159); hypodiploidy - 3.1% (5/159); hyperdiploidy - 1.25% (2/159); del5q - 0,6% (1/159); other - not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (>3 aberrations) - in 4.4% (7/159) patients. The median OS in "two aberration" and "complex abnormalities" groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 26 months and was not reached, respectively (p=.00015). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p=.011). Differences between "two aberration" and "complex abnormalities" groups were not find (p> .05). We modified high-risk (gain 1q, p53 mutation, del 17p deletion, t(4;14), t(14;16), t(14;20), R-ISS stage III, double and triple hit myeloma) mSMART 3.0 by adding "two aberration" and "complex abnormalities" groups on based the OS and PFS results. The final analysis was based on the results of the complex examination of 87 patients: 53 patients in standard-risk group and 34 patients in high-risk group. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0mod - 48 months; 5-years OS was 62% and 38%, respectively (p=0.0073). The median PFS was 43 and 29 months, respectively (p=.09). The best results of OS and PFS were reach in both groups of patient who performed ASCT. The median OS in standard-risk mSMART 3.0 with ASCT (n=37) was not reached, in high-risk mSMART 3.0mod with ASCT - 48 months (n=20); standard-risk mSMART 3.0 without ASCT - 40 months (n=16); in high-risk mSMART 3.0mod without ASCT - 22 months (n=14); 5-years OS was 81%, 60%, 33% and 28%, respectively (p=0.0015). The median PFS was not reached, 46, 22 and 19 months, respectively (p=.017). Conclusions The combination of two aberrations and complex abnormalities is unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk group according mSMART 3.0mod. The ASCT can improve treatment's outcomes and life expectancy especially in patients with high-risk. It can be useful for update risk stratification in a future. Disclosures Shuvaev: Novartis: Consultancy; Pfize: Honoraria; Fusion Pharma: Consultancy; BMS: Consultancy.

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Real-World Treatments and Thrombotic Events in Polycythemia Vera Patients: A Retrospective Analysis between 2018-2019 in US Population

Blood ◽

10.1182/blood-2020-142549 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 1-2

Author(s):

Srdan Verstovsek ◽

Ariel Han ◽

Karin Chun Hayes ◽

Tracy Woody ◽

Frank Valone ◽

...

Keyword(s):

High Risk ◽

Real World ◽

Blood Cells ◽

Initial Treatment ◽

Research Funding ◽

Treatment Initiation ◽

Low Risk ◽

High Risk Patients ◽

Risk Patients

BACKGROUND Polycythemia Vera (PV) is a rare myeloproliferative neoplasm associated with an increased production of red blood cells, white blood cells, and platelets. Most frequent treatment includes phlebotomy, hydroxyurea, interferon, and ruxolitinib. Current NCCN guideline recommends managing HCT levels to below 45%. The objective of this study was to determine real-world standards of care and patient characteristics, and to observe how treatment decisions vary by HCT level and thrombosis risk. METHODOLOGY We conducted a retrospective study using Symphony Health's longitudinal transactional healthcare claims database that includes prescription, medical and hospital claims across > 4,900 US payers representing 86% of US lives. Eligible patients had at least one ICD-10 diagnosis code for PV and at least one of the treatments including phlebotomy, hydroxyurea, busulfan, interferon, and ruxolitinib between Jan 1, 2018 and Dec 31, 2019 (index period). For eligible patients, all prior treatment history initiated as far back as January 2010 was used to report therapy changes. Patients were also required to have at least one PV diagnosis within a year of treatment initiation and at least 2 HCT lab results during the index period. PV treatment changes and characteristics were studied. RESULTS Out of 28,306 patients with PV, 4,264 patients had HCT lab data for 2 years (index period). Median duration of follow-up was 854 days (range 98-3,373days). Patient therapy duration was from 1 to 9 years. Median patient age was 65 (range 11-94), with 1,451 (34%) patients aged less than 60, 2,813 (66%) 60 years or older, and a substantial male predominance (62% vs 38%). 1,247 (29%) patients were classified as Low Risk (age< 60 with no TE history) and 3,017 (71%) patients as High Risk. Within the High-Risk group, 2,224 (52%) were age>60 without prior TE, 204 (5%) were age<60 with prior TE and 589 (14%) were age>60 with prior TE. For Low Risk patients' initial treatment was phlebotomy alone (85%) and a total of 73% of all Low Risk patients remained on phlebotomy alone. For High Risk patients' initial treatment was phlebotomy alone (60%) and 43% all of High-Risk patients remained on phlebotomy alone (Figure 1). The median HCT prior to treatment initiation was 52.9% and 48% during treatment. 936 (22%) patients achieved NCCN treatment guidelines with HCT levels always remaining under 45%, and 1,226 (29%) patients had HCT levels controlled between 45% and 50%. However, 2,102 (49%) patients had some or all HCT levels> 50% (Figure 2). With the most recent lab test, 2,180 (51%) of patients still had HCTs above 45% and 804 (19%) were still above 50%. In a sub-cohort of 653 High Risk patients with a prior TE and up to 5 years of follow up, 236 (36%) had at least one other TE; for the 1,774 High Risk patients who did not have the history of thrombosis, 161(9%) had at least one TE (Table 2). The most common TE since treatment began in patients with prior TE were deep vein thrombosis (n= 92 patients, 14%) and stroke (n= 95 patients, 15%). Among High Risk patients (n=397) who had another thrombotic event, 180 (45%) were treated by phlebotomy only and never switched to any other therapies. CONCLUSIONS Despite currently available treatments in US, patients' HCT level after treatment were higher than recommended as per guidelines. Failure to maintain HCT less than 45% increases the risk of future thrombotic events as shown by 36% of patients with prior TE experiencing another TE within the next 5 years. Disclosures Verstovsek: Sierra Oncology: Consultancy, Research Funding; ItalPharma: Research Funding; Blueprint Medicines Corp: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Incyte Corporation: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; PharmaEssentia: Research Funding; Genentech: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; CTI Biopharma Corp: Research Funding. Han:Protagonist Therapeutics: Consultancy. Chun Hayes:Protagonist: Consultancy. Woody:Protagonist: Current Employment. Valone:Protagonist: Current Employment. Gupta:Protagonist: Current Employment.

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Treatment Sequencing Patterns Associated with Elderly Patients with Relapsed/Refractory Multiple Myeloma (MM) in the US Community Setting

Blood ◽

10.1182/blood.v126.23.5392.5392 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5392-5392 ◽

Cited By ~ 2

Author(s):

Amanda M Farr ◽

Marni Stott-Miller ◽

Helen Varker ◽

Danae Spencer ◽

Manan Shah ◽

...

Keyword(s):

Elderly Patients ◽

Treatment Options ◽

Treatment Patterns ◽

Cell Transplant ◽

Community Practice ◽

Duration Of Treatment ◽

Free Interval ◽

The Us ◽

Treatment Sequencing

Abstract Background: With more targeted agents in development, the treatment of relapsed/refractory MM has become more complicated and, as a consequence, has resulted in great heterogeneity in treatment patterns. Little is known about treatment sequences in the US community practice setting for elderly patients. The goal of this study was to describe treatment sequencing patterns in elderly MM patients. Methods: A retrospective cohort study of patients (≥65 years old) with newly diagnosed MM between 7/1/2011 and 5/31/2014 who had ≥2 oncologist visits within 90 days after diagnosis and ≥90 days of follow-up was conducted. Patients were selected from the Truven MarketScan Oncology Electronic Medical Records (EMR) database and followed until last visit in the EMR database or 8/31/2014, whichever occurred first. First-line (1L) treatment included treatment that a patient received since first anti-MM prescription/administration. For any given line of therapy, the end of treatment was defined as the first day of any gap in treatment >90 days or initiation of a new regimen. Treatment patterns for 1L, second-line (2L), and third-line (3L) treatment were described. Duration of treatment and treatment-free intervals were analyzed using Kaplan-Meier (K-M) methods. Results: 2,896 MM patients met the selection criteria and initiated anti-MM therapy in the study period. Of these, 1,032 (36%) patients (median age 75 years, 55% male) received 2L treatment and 352 (12%) received 3L treatment. The median patient follow-up for those who received 2L treatment was 19.2 months. Of the 1,032 patients with 2L treatment, 715 (69%) received a proteasome inhibitor (PI=bortezomib, carfilzomib) or an immunomodulatory drug (IMiD=lenalidomide, pomalidomide, thalidomide) and 317 (31%) received conventional chemotherapy (CT) or steroid (S) only (Table 1). 16% received a stem cell transplant at any time. Of the 352 patients with 3L treatment, 227 (64%) received a PI or IMiD, and 125 (36%) received CT or S only (Table 1). The use of carfilzomib and pomalidomide increased slightly from 1L to 3L (Table 2). Of the 374 patients who received 2L IMiD, over 80% received a PI or IMiD in 1L treatment (PI: 45%, IMiD: 22%, both: 15%); of those who received an IMiD in both 1L and 2L, 86% repeated the IMiD received in 1L and 9% switched to pomalidomide. Of the 307 patients who received 2L PI, >80% received a PI or IMiD in 1L treatment (PI: 57%, IMiD: 22%, both: 5%); of those who received a PI in both 1L and 2L, 72% repeated the PI received in 1L and 26% switched to carfilzomib. Similarly, of the 124 patients who received 3L IMiD, most received a PI or IMiD in 2L (PI: 13%, IMiD: 47%, both: 3%). The same was true of the 92 patients who received 3L PI (PI: 28%, IMiD: 45%, both: 3% in 2L treatment). Of the 352 patients with 1L-3L treatment, 93% received a PI or IMiD in 1L, 2L, or 3L; 32% had a PI or IMiD in all 3 lines. Median duration of 1L, 2L, and 3L treatment was 196, 148, and 124 days, respectively (Table 3). Median treatment-free interval from end of 1L to initiation of 2L, and from end of 2L to initiation of 3L, was 175 and 137 days, respectively (Table 3). Conclusions: The data suggest that elderly MM patients run out of treatment options when they fail 1L/2L treatment; therefore, duration of treatment as well as treatment-free interval decreases as disease progresses. These findings highlight the unmet needs for newer therapies in elderly MM patients who fail prior anti-MM treatment. Table 1. 2L and 3L treatment for first- and second-relapsed elderly MM patients PI or IMiD, n (%) CT, n (%) S, n (%) n All PI only IMiD only Both 2L 1,032 715 (69) 307 (30) 374 (36) 34 (3) 78 (8) 239 (23) 3L 352 227 (64) 92 (26) 124 (35) 11 (3) 26 (7) 99 (28) Table 2. Use of carfilzomib and pomalidomide among the 1,032 patients in 1L, 2L and 3L treatment Treatment n Carfilzomib, n (%) Pomalidomide, n (%) 1L 2,896 99 (3) 15 (1) 2L 1,032 72 (7) 41 (4) 3L 352 32 (9) 23 (7) Table 1. K-M estimates of duration of treatment and treatment-free interval for 1L, 2L, and 3L treatment in elderly patients with MM K-M Estimate 95% CI Treatment duration, days 1L (n=2,896) 196 180-208 2L (n=1,032) 148 127-165 3L (n=352) 124 100-194 Treatment-free interval, days 1L to 2L (n=1,596) 175 164-191 2L to 3L (n=507) 137 127-157 Disclosures Farr: Truven Health Analytics: Employment, Other: I am employed by Truven Health Analytics which received funding from Bristol-Myers Squibb to conduct this analysis. Stott-Miller:Truven Health Analytics: Employment, Other: I am an employee of Truven Health Analytics which received funding from Bristol-Myers Squibb to conduct this analysis. Varker:Truven Health Analytics: Employment, Other: I am an employee of Truven Health Analytics which received funding from Bristol-Myers Squibb to conduct this analysis. Spencer:Truven Health Analytics: Employment, Other: I am an employee of Truven Health Analytics which received funding from Bristol-Myers Squibb to conduct this analysis. Shah:Bristol-Myers Squibb: Employment, Other: Stocks. Chen:Bristol-Myers Squibb: Employment.

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Long-Term Follow-Up Results of Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy and Risk-Adapted Maintenance Approach in Newly Diagnosed Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.19.02515 ◽

2020 ◽

Vol 38 (17) ◽

pp. 1928-1937 ◽

Cited By ~ 14

Author(s):

Nisha S. Joseph ◽

Jonathan L. Kaufman ◽

Madhav V. Dhodapkar ◽

Craig C. Hofmeister ◽

Dhwani K. Almaula ◽

...

Keyword(s):

High Risk ◽

Induction Therapy ◽

Newly Diagnosed ◽

Long Term Outcomes ◽

Entire Cohort ◽

Induction Regimen ◽

Risk Patients ◽

Standard Risk

PURPOSE The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a highly effective and convenient induction regimen for both transplantation-eligible and -ineligible patients with myeloma. Here, we present the largest cohort of patients consecutively treated with RVD induction therapy followed by risk-adapted maintenance therapy with the longest follow-up and important information on long-term outcomes. PATIENTS AND METHODS We describe 1,000 consecutive patients with newly diagnosed myeloma treated with RVD induction therapy from January 2007 until August 2016. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board–approved myeloma database. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. RESULTS The overall response rate was 97.1% after induction therapy and 98.5% after transplantation, with 89.9% of patients achieving a very good partial response (VGPR) or better and 33.3% achieving stringent complete response after transplantation at a median follow-up time of 67 months. The estimated median progression-free survival time was 65 months (95% CI, 58.7 to 71.3 months) for the entire cohort, 40.3 months (95% CI, 33.5 to 47 months) for high-risk patients, and 76.5 months (95% CI, 66.9 to 86.2 months) for standard-risk patients. The median overall survival (OS) time for the entire cohort was 126.6 months (95% CI, 113.3 to 139.8 months). The median OS for high-risk patients was 78.2 months (95% CI, 62.2 to 94.2 months), whereas it has not been reached for standard-risk patients. Five-year OS rates for high-risk and standard-risk patients were 57% and 81%, respectively, and the 10-year OS rates were 29% and 58%, respectively. CONCLUSION RVD is an induction regimen that delivers high response rates (VGPR or better) in close to 90% of patients after transplantation, and risk-adapted maintenance can deliver unprecedented long-term outcomes. This study includes the largest cohort of patients treated with RVD reported to date with long follow-up and demonstrates the ability of 3-drug induction regimens in patients with newly diagnosed multiple myeloma to result in a substantial survival benefit.

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220 Real-world outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0220 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A239-A239

Author(s):

Wolfram Samlowski ◽

Robert Nicholas ◽

Tayla Poretta ◽

Andriy Moshyk ◽

Jonathan Rajkumar ◽

...

Keyword(s):

Overall Survival ◽

Real World ◽

Treatment Patterns ◽

Stage Iii ◽

List Type ◽

Stage Iiia ◽

American Joint Committee ◽

The Us ◽

Resected Stage

BackgroundNivolumab is approved in the US and EU for the adjuvant treatment of resected stage III-IV melanoma based on results from the CheckMate-238 clinical trial.1,2 However, the trial did not enroll any patients with Stage IIIA disease per the American Joint Committee on Cancer (AJCC) 7th edition criteria and included a limited number of patients with stage IIIA disease per the AJCC 8th edition.3,4,5Recognizing the need for real-world data to assess outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab, a non-interventional study was conducted to investigate treatment patterns and outcomes among patients receiving adjuvant nivolumab within the US community practice setting.MethodsA retrospective analysis of the US Oncology Network’s iKnowMed medical data was conducted to examine patients with resected stage IIIA melanoma treated with adjuvant nivolumab between 01-Jan-2018 and 31-Dec-2019 with a follow-up period through 31-Mar-2020. Patients were followed for up to 27 months after their sentinel lymph node biopsy. Baseline demographic/clinical characteristics and treatment patterns were examined descriptively. Duration of treatment (DOT) and overall survival were analyzed using the Kaplan-Meier method.ResultsA total of 58 patients with stage IIIA melanoma treated with adjuvant nivolumab were identified. Median age was 57.8 years (range 21.5–93.5), 62.1% were male, and 75.9% were Caucasian. Among patients with a documented Eastern Cooperative Oncology Group (ECOG) performance status (51.7%), all had an ECOG score of 0 or 1. Median follow-up time was 12.6 months (range 0.3–25.1). Median DOT was 10.6 months (range 6.8–12.0). Overall survival rates at 12 and 24 months were 97.7% (95% CI 84.6–99.7) and 92.2% (95% CI 69.6–98.2), respectively.ConclusionsThis real-world analysis of patients with stage IIIA melanoma treated with adjuvant nivolumab showed that a large proportion of patients were alive at the end of the study period, suggesting these patients have a favorable prognosis. Further investigation and follow-up is warranted to assess clinically relevant outcomes among patients with resected stage IIIA melanoma.Ethics ApprovalThe study was approved by US Oncology Inc’s Institutional Review Board, approval number 20-020E-2020-0224-01.ReferencesWeber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. NEJM 2017;377:1824–35.Weber J, Mandala M, Del Vecchio M, et al. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: A randomized, double-blind, phase 3 trial (CheckMate 238). Ann Oncol 2017;28(5):632–33.Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27(36):6199–6206.Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017;67(6):472–492.National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma Version 3.2020 - May 18, 2020. 2020.

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