Real-World Survival Among Patients with Intermediate- to High-Risk Myelofibrosis in the United States: Impact of Ruxolitinib Approval

Background The myeloproliferative neoplasm myelofibrosis (MF) is associated with reduced overall survival (OS) compared with the general population (Hultcrantz M, et al. J Clin Oncol. 2012;30[24]:2995-3001; Price GL, et al. PLoS One. 2014;9[3]:e90299). The Janus kinase 1 and 2 inhibitor ruxolitinib (RUX) was approved by the US Food and Drug Administration in November 2011 for the treatment of adult patients with intermediate- or high-risk MF based on data from the phase 3 COMFORT trials, which showed significantly improved OS in patients who received RUX (Verstovsek S, et al. J Hematol Oncol. 2017;10:156). Understanding the clinical benefit of RUX in real-world practice requires an understanding of changes in patient outcomes for those exposed to RUX compared with those never exposed to RUX, both before and after approval. The aim of this analysis was to assess the OS of patients newly diagnosed with intermediate- to high-risk MF before RUX approval, and for those who were RUX-unexposed vs -exposed in the post-RUX approval time frame. Study Design and Methods All data from the Medicare Fee-for-Service claims database (Parts A/B/D) from January 2010 to December 2017 were used to identify patients who were ≥65 years old (intermediate-1 or higher risk MF due to age) with ≥1 inpatient claim or ≥2 outpatient claims with a documented MF diagnosis. The index date was the date of the first qualifying MF claim; ≥12 months of pre-index continuous medical and pharmacy enrollment was required. Patients with evidence of an MF diagnosis ≤12 months before the index date were excluded. Patients with a diagnosis of myelodysplastic syndrome, hematologic malignancies (leukemias, multiple myeloma, and lymphomas), or solid tumors either ≤12 months before, on, or any time after index were also excluded in a stepwise manner. The study sample was classified into 3 groups: patients diagnosed with MF pre-RUX approval (index year 2010-2011; no post-index exposure to RUX); those diagnosed with MF post-RUX approval and unexposed to RUX (index year 2012-2017); and those diagnosed with MF post-RUX approval and exposed to RUX (index year 2012-2017). One-year survival rate and risk of mortality were estimated using Kaplan-Meier and Cox proportional hazards regression analyses, adjusting for baseline demographic and clinical characteristics. OS was measured from the index date until death or end of follow-up. Patients without a death date were censored at disenrollment or the end of the study period, whichever occurred first. Results Among eligible patients with an MF diagnosis (N=1677), median age was 78 years, 39.8% were male, and 84.1% were white. The analysis included 278 patients diagnosed pre-RUX approval (all RUX-unexposed) and 1399 diagnosed post-RUX approval (RUX-unexposed, n=1127; RUX-exposed, n=272). Median follow-up for the pre- and post-RUX approval groups was 12.5 and 11.3 mo (RUX-unexposed, 10.2 mo; RUX-exposed, 14.0 mo), respectively. In the pre-RUX approval group, 119 (42.8%) patients had a valid death date compared with 436 (31.2%) in the post-RUX approval group (RUX unexposed, n=382 [33.9%]; RUX exposed, n=54 [19.9%]). The 1-year survival rate (95% CI) was 55.6% (49.4%-61.3%) for the pre-RUX approval group, 72.5% (69.5%-75.2%) for the post-RUX approval RUX-unexposed group, and 82.3% (76.7%-86.7%) for the post-RUX approval RUX-exposed group (Figure). The risk of mortality was lowest among RUX-exposed patients (adjusted hazard ratio [HR], 0.36; 95% CI, 0.26-0.50; P<0.0001 vs the pre-RUX approval group). Patients in the post-RUX approval group who had never been exposed to RUX also had a lower risk of mortality, although less pronounced than RUX-exposed patients, compared with the pre-RUX approval group (adjusted HR, 0.67; 95% CI, 0.56-0.80; P<0.0001). Conclusions In this real-world study of US patients diagnosed with intermediate- or high-risk MF, 1-year OS was improved in patients diagnosed after RUX approval compared with before RUX approval. Notably, in the post-RUX approval time frame, 1-year OS was greater for those who received RUX than for those who did not receive RUX. These findings complement the survival benefit results demonstrated in the COMFORT studies using real-world data. Disclosures Verstovsek: Gilead: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; Incyte Corporation: Consultancy, Research Funding; CTI Biopharma Corp: Research Funding; Celgene: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; AstraZeneca: Research Funding; ItalPharma: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Roche: Research Funding; Promedior: Research Funding. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Shah:Avalere Health: Current Employment. Kumar:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Xi:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Harrison:Gilead Sciences: Honoraria, Speakers Bureau; CTI Biopharma Corp: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria; Sierra Oncology: Honoraria; Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Incyte Corporation: Speakers Bureau; AOP Orphan Pharmaceuticals: Honoraria; Promedior: Honoraria.

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Thrombosis and Risk of Mortality in Newly Diagnosed High-Risk Polycythemia Vera: An Analysis of the Medicare Claims Database in the United States

Blood ◽

10.1182/blood-2020-141370 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 9-10

Author(s):

Naveen Pemmaraju ◽

Aaron T. Gerds ◽

Shreekant Parasuraman ◽

Jingbo Yu ◽

Anne Shah ◽

...

Keyword(s):

High Risk ◽

Median Time ◽

Research Funding ◽

Index Date ◽

Newly Diagnosed ◽

Publicly Traded ◽

Risk Of Mortality ◽

Increased Risk ◽

History Of

Background Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with an increased risk of thrombotic events (TEs), a major cause of morbidity and mortality. Patients aged ≥60 years and/or with a history of thrombosis are considered to have high-risk PV. There is limited contemporary, real-world evidence exploring the effect of TEs on mortality in patients with PV. The aim of this analysis was to compare the risk of mortality in patients newly diagnosed with high-risk PV who experienced a TE vs those who did not experience a TE. Study Design and Methods All data from the Medicare Fee-for-Service (FFS) claims database (Parts A/B/D) from January 2010-December 2017 were used to identify patients with a PV diagnosis (all high risk based on cohort being ≥65 years of age) with ≥1 inpatient or ≥2 outpatient claims. The index date was the date of the first qualifying PV claim. Patients with a PV diagnosis or use of cytoreductive therapy within 12 months before the index date (pre-index period) were excluded; ≥12-months continuous medical and pharmacy enrollment pre-index dates was required. The study sample was categorized into TE and non-TE groups based on the occurrence of any of the following events during follow-up: deep vein thrombosis, pulmonary embolism, ischemic stroke, acute myocardial infarction, transient ischemic attack, peripheral arterial thrombosis, or superficial thrombophlebitis. TEs were evaluated from the index date to the end of follow-up. Cox regression analyses with time-varying effects were used to assess mortality risk among patients with PV, with post-index TE as a time-dependent variable, stratified by pre-index TE, and adjusting for patient demographic characteristics and comorbid conditions. Results A total of 56,176 Medicare FFS beneficiaries with PV diagnoses met inclusion criteria. The median age was 73 years, 51.9% were men, and 90.7% were white; 10,110 patients (18.0%) had a history of TE before diagnosis (ie, pre-index). In the follow-up period, 20,105 patients (35.8%) had a TE and 36,071 patients (64.2%) did not have a TE. In the comparison between the TE vs non-TE groups, the median (range) age (75.0 [65-104] vs 73.0 [65-106] years, respectively), mean (SD) Charlson comorbidity index score (3.1 [2.6] vs 2.2 [2.3]), and percentage of patients with a history of cardiovascular events (34.1% vs 23.8%), bleeding (13.3% vs 10.4%), or anemia (28.6% vs 23.4%) were higher (Table 1). Among all patients with PV, the median time from diagnosis to first post-index TE was 7.5 months. Among those with pre-index TE (n=10,093), median time from index to first post-index TE was 0.6 months, whereas patients without pre-index TE (n=46,083) had a median time to first post-index TE of 14.2 months. Among all patients with TE during follow-up, the most common TEs were ischemic stroke (47.5%), transient ischemic attack (30.9%), and acute myocardial infarction (30.5%). The risk of mortality was increased for patients who experienced a TE compared with those who did not (hazard ratio [HR; 95% CI], 9.3 [8.4-10.2]; P<0.0001). For patients who experienced a pre-index TE, the risk of mortality was increased for patients who experienced a subsequent TE during follow-up compared with patients who did not (HR [95% CI], 6.7 [5.8-7.8]; P<0.0001). Likewise, for patients who did not experience a pre-index TE, the risk of mortality was increased for patients who experienced a TE during follow-up compared with patients who did not (HR [95% CI], 13.1 [11.4-15.0]; P<0.0001). Conclusions In this real-world study, approximately one-third of patients with newly diagnosed high-risk PV experienced a TE during follow-up and had a 9-fold increased risk of mortality vs those who did not experience a TE. TE risk mitigation remains an important management goal in patients with PV, particularly in those with prior TE. Disclosures Pemmaraju: Samus Therapeutics: Research Funding; Celgene: Honoraria; SagerStrong Foundation: Other: Grant Support; Affymetrix: Other: Grant Support, Research Funding; MustangBio: Honoraria; Blueprint Medicines: Honoraria; LFB Biotechnologies: Honoraria; Plexxikon: Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Stemline Therapeutics: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Daiichi Sankyo: Research Funding; Incyte Corporation: Honoraria; Roche Diagnostics: Honoraria; Cellectis: Research Funding; DAVA Oncology: Honoraria. Gerds:Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Gilead Sciences: Research Funding; Imago Biosciences: Research Funding; Pfizer: Research Funding; CTI Biopharma: Consultancy, Research Funding; Roche/Genentech: Research Funding; Apexx Oncology: Consultancy; AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Shah:Avalere Health: Current Employment. Xi:Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation; Avalere Health: Current Employment. Kumar:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Gilead: Research Funding; Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; CTI Biopharma Corp: Research Funding; Promedior: Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; Sierra Oncology: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; ItalPharma: Research Funding; PharmaEssentia: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding.

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Thrombotic Events and Mortality Risk in Patients Newly Diagnosed with Intermediate- to High-Risk Essential Thrombocythemia in the United States

Blood ◽

10.1182/blood-2020-141333 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 21-21

Author(s):

Naveen Pemmaraju ◽

Aaron T. Gerds ◽

Jingbo Yu ◽

Shreekant Parasuraman ◽

Anne Shah ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Index Date ◽

Newly Diagnosed ◽

Publicly Traded ◽

Risk Of Mortality ◽

Grant Support ◽

Increased Risk ◽

Ischemic Attack

Background Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) associated with an increased risk of thrombotic events (TEs), which represent a substantial cause of mortality in this population. There is limited contemporary, real-world evidence exploring the effect of TEs on mortality in patients with ET. The aim of this analysis was to compare risk of mortality among patients newly diagnosed with intermediate- or high-risk ET who experienced a TE vs those who did not experience a TE. Study Design and Methods All data from the Medicare Fee-for-Service (FFS) claims database (Parts A/B/D) from January 2010-December 2017 were used to identify patients with an ET diagnosis (all intermediate or high risk based on cohort age ≥65 years) with ≥1 inpatient or ≥2 outpatient claims. The index date was the date of the first qualifying ET claim. Patients with an ET diagnosis, use of hydroxyurea, or use of ruxolitinib within 12 months before the index date and patients with a myelofibrosis diagnosis during the study period were excluded. A minimum of 12 months of continuous medical and pharmacy enrollment pre-index was required. The study sample was categorized into TE and non-TE groups based on the occurrence of any of the following events during follow-up: deep vein thrombosis, pulmonary embolism, ischemic stroke, acute myocardial infarction, transient ischemic attack, peripheral arterial thrombosis, or superficial thrombophlebitis. TEs were evaluated from the index date to the end of follow-up. Cox regression analyses with time-varying effects were used to assess mortality risk among patients with ET with post-index TE as a time-dependent variable, stratified by pre-index TE, and adjusting for patient demographic characteristics and comorbid conditions. Results A total of 143,588 Medicare FFS beneficiaries with a diagnosis of ET met the study inclusion criteria; median age was 76.0 years, 68.1% were female, and 84.2% were white. Pre-index TE was reported in 37,284 patients (26.0%). In the follow-up period, 49,497 patients (34.5%) had a TE and 94,091 patients (65.5%) did not have a TE. In the comparison between the TE vs non-TE groups, the median (range) age (77 [65-107] vs 75 [65-110] years, respectively), mean (SD) Charlson comorbidity index score (4.8 [3.5] vs 3.8 [3.5]), and percentage of patients with a history of bleeding (27.0% vs 22.2%), anemia (64.7% vs 55.9%), or a cardiovascular event (45.8% vs 33.5%) were higher (Table 1). The median time from ET diagnosis to first TE in the follow-up period was 2.8 months for all patients, 0.5 months for patients with pre-index TE, and 8.0 months for those without pre-index TE. The most common types of first TE in the follow-up period were ischemic stroke (37.3%), acute myocardial infarction (23.2%), and transient ischemic attack (22.6%). The risk of mortality was increased for patients who experienced a TE compared with those who did not (hazard ratio [HR; 95% CI], 11.2 [10.6-11.8]; P<0.001), including for both those with pre-index TE (HR [95% CI], 9.3 [8.6-10.1]; P<0.001) and those without pre-index TE (HR [95% CI], 15.4 [14.2-16.8]; P<0.001). Conclusions In this contemporary, real-world analysis, approximately one-third of patients with newly diagnosed intermediate- to high-risk ET experienced a TE. Elderly patients with ET who experienced a TE had an approximately 11-fold increased risk of mortality vs those who did not experience a TE, highlighting a continued unmet need in this population. Further efforts are needed to better define and mitigate TE risk in patients with ET, particularly in those with prior TE. Disclosures Pemmaraju: Daiichi Sankyo: Research Funding; Cellectis: Research Funding; Plexxikon: Research Funding; Blueprint Medicines: Honoraria; AbbVie: Honoraria, Research Funding; Samus Therapeutics: Research Funding; Affymetrix: Other: Grant Support, Research Funding; Roche Diagnostics: Honoraria; Stemline Therapeutics: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Incyte Corporation: Honoraria; Novartis: Honoraria, Research Funding; LFB Biotechnologies: Honoraria; MustangBio: Honoraria; Celgene: Honoraria; DAVA Oncology: Honoraria; SagerStrong Foundation: Other: Grant Support. Gerds:Gilead Sciences: Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche/Genentech: Research Funding; AstraZeneca/MedImmune: Consultancy; Imago Biosciences: Research Funding; Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy, Research Funding; Pfizer: Research Funding. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Shah:Avalere Health: Current Employment. Xi:Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation; Avalere Health: Current Employment. Kumar:Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation; Avalere Health: Current Employment. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Verstovsek:CTI Biopharma Corp: Research Funding; Protagonist Therapeutics: Research Funding; Roche: Research Funding; Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; PharmaEssentia: Research Funding; Sierra Oncology: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; AstraZeneca: Research Funding; ItalPharma: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Celgene: Consultancy, Research Funding; NS Pharma: Research Funding.

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Real-World Effectiveness of Voxelotor for Treating Sickle Cell Disease in the US

Blood ◽

10.1182/blood-2020-140525 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 25-25

Author(s):

Ahmar Urooj Zaidi ◽

Thokozeni Lipato ◽

Ofelia A. Alvarez ◽

Alexander Lonshteyn ◽

Derek Weycker ◽

...

Keyword(s):

Board Of Directors ◽

Real World ◽

Research Funding ◽

Index Date ◽

Health Claims ◽

Transfusion Rate ◽

Publicly Traded ◽

Advisory Committees ◽

The Us

Background: Until late 2019, few treatments had been approved by the FDA for treating sickle cell disease (SCD). Voxelotor (Oxbryta®) is a sickle hemoglobin-polymerization inhibitor approved by the FDA in November 2019 for treatment of SCD in adults and adolescents aged ≥12 years under an accelerated approval based on results of the pivotal HOPE study. In HOPE, voxelotor increased average hemoglobin (Hb) by 1.1 g/dL from baseline in patients with 1-10 vaso-occlusive crises (VOCs) in the previous year and a Hb level between 5.5 and 10.5 g/dL who were not transfusion dependent. Of the participants on voxelotor 1500 mg, 51% had a Hb response >1.0 g/dL at week 24 (Vichinsky et al, NEJM 2019). This study sought to assess the real-world effectiveness of voxelotor based on data during the first 6 months post FDA approval. Methods: Data on medical and pharmacy claims for patients who were aged ≥12 years and receiving voxelotor from December 2019 to May 2020 were obtained from the Symphony Health claims dataset. For each patient, the date of the first voxelotor claim was defined as the "index date." Patients with at least 1 year's data prior to the index date were included in the analyses. Patients' demographic and clinical characteristics were summarized descriptively. Standardized annualized rates of transfusions and VOCs per patient per year (PPPY) prior to and after voxelotor initiation were compared. A subset of patients in the Symphony Health claims dataset had Hb lab data available. Patients with at least 1 Hb result within 30 days prior to the index date and at least 1 Hb result after the index date were included for Hb analyses. For these patients, change in Hb and the percentage of patients achieving a >1 g/dL increase in Hb were summarized. Confidence intervals and P values for changes in outcomes were based on bootstrapping. Results: As of May 31, 2020, 1275 patients from the Symphony Health claims datasets were identified who received voxelotor (40% male, mean age 35.7 years). In the year prior to voxelotor initiation, 715 (56.1%) of these patients received hydroxyurea, 121 (9.5%) received L-glutamine, 166 (13.0%) received at least 1 transfusion, 17 (1.3%) were on chronic transfusion (≥8 transfusions per year), and 681 (53.4%) had 1 or more VOCs. Mean (SD) follow-up was 64.9 (40.7) days. Among 1275 patients, 175 and 52 patients had at least 1 Hb level measurement during the 1 year prior to and after voxelotor initiation, respectively. Among the subset of patients with their Hb level tested within 30 days prior to the index date and at least 1 Hb level after index date (n=22), the baseline average Hb level was 8.0 g/dL (SD 1.4, median 7.9 g/dL, range 5.0-11.8 g/dL). Mean increase in Hb from baseline was 1.1-1.3 g/dL (Table 1) depending on the approach used to calculate Hb levels after voxelotor initiation; 55% (95% CI 32%-77%) of patients achieved a Hb increase >1 g/dL after voxelotor initiation. Among all 1275 patients, mean (SD) overall transfusion rates declined from 0.45 (1.67) PPPY pre-index to 0.31 (1.88) post-index, a change of -0.14 PPPY (P=0.005). Among 169 patients who received at least 1 transfusion in the year prior to initiation of voxelotor, the transfusion rate dropped from 3.39 (3.34) to 1.75 (4.30) PPPY, a change of -1.64 PPPY (P<0.001). Among 17 patients receiving chronic transfusions, the transfusion rate dropped from 11.29 (3.12) to 6.74 (7.37) PPPY, a change of -4.56 PPPY (P=0.013) (Table 2). After voxelotor initiation, the annualized rates of VOC were numerically reduced from 3.86 (6.69) to 3.64 (8.54) (P=0.248). To address the potential bias from the relatively short follow-up duration, similar results of transfusion and VOC rates were observed among patients with at least 30 days of follow-up or when only events within 3 months prior to index date were considered. Conclusions: Based on the first 6 months' data after the approval of voxelotor in the US, in real-world practice, voxelotor increases Hb by at least 1 g/dL, consistent with the HOPE randomized controlled trial results. Evidence suggests that transfusion rates decreased after voxelotor initiation. A favorable downward trend in VOC rates was also observed. This real-world evidence provides additional support for the use of this novel therapy in the treatment of hemolytic anemia and its associated complications in the SCD population. Further evaluation with a larger sample size and longer follow-up will help to confirm these findings. Disclosures Zaidi: Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria; Cyclerion: Consultancy, Honoraria; Imara: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; Emmaus Life Sciences: Consultancy, Honoraria. Alvarez:Novartis: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees. Lonshteyn:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Weycker:Policy Analysis Inc.: Current Employment, Current equity holder in publicly-traded company; Novartis: Research Funding; Global Blood Therapeutics: Research Funding. Pham:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Delea:Global Blood Therapeutics: Research Funding; Novartis: Research Funding; Policy Analysis Inc.: Current Employment, Current equity holder in private company. Agodoa:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Cong:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Alexion: Speakers Bureau; Bluebird Bio: Consultancy.

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Real-World Treatment Patterns Among a Contemporary Cohort of Commercially Insured Mantle Cell Lymphoma Patients in the United States

Blood ◽

10.1182/blood-2018-99-112532 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4845-4845

Author(s):

Lindsey E. Roeker ◽

Shaum Kabadi ◽

Chakkarin Burudpakdee ◽

Aimee Near ◽

Keiko Wada ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Research Funding ◽

Index Date ◽

Treatment Patterns ◽

Treatment Regimens ◽

Oral Medications ◽

Mantle Cell ◽

Insured Patients

Abstract Introduction Mantle cell lymphoma (MCL) is a rare, aggressive non-Hodgkin lymphoma associated with a poor prognosis. The approval of ibrutinib in November 2013 has changed the treatment paradigm for patients with relapsed or refractory MCL. There remains a lack of information on the current treatment patterns used in clinical practice in a contemporary cohort of commercially insured patients. We aimed to identify the treatment patterns for MCL overall and by line of therapy (LOT) and to describe patient demographics and clinical characteristics in a large cohort of commercially insured MCL patients. Methods A retrospective cohort study was conducted with the IQVIA Real-World Data Adjudicated Claims-US database. Adult patients (≥18 years old) with ≥1 claim for a NCCN-recommended MCL treatment between November 1, 2013 and December 31, 2017 were identified. Index date was the first treatment claim. Patients were also required to have ≥1 diagnosis of MCL during the study period (November 1, 2012 to January 31, 2018), ≥12 months of continuous enrollment prior to index date (pre-index period) and ≥30 days after index date (follow-up period). Patients were excluded if they were ≥65 years at index and not enrolled in Medicare Risk or Medicare Cost, enrolled in a clinical trial during the study period, had evidence of MCL treatment in the pre-index period (except for patients indexed on ibrutinib as it is indicated for MCL patients with ≥1 prior treatment), or had evidence of stem cell transplant (SCT) before index date. The most commonly observed MCL treatment regimens were identified, and demographic and clinical characteristics of patients and treatment durations by regimen were described. Treatment regimen was defined as the combination of all agents observed in the 35-day period after the first MCL treatment claim; treatment duration was defined as the start of treatment until a gap of ≥90 days between end date and next date of treatment or treatment modification. Treatment end date occurred 90 days after the end of the supply for oral medications or 30 days after the last administration for non-oral medications. Results There were 1,785 patients treated with the most commonly observed MCL treatment regimens. The most common regimens, irrespective of LOT, were rituximab monotherapy (including maintenance therapy; n=773, 43.3%), R-CHOP (n=723, 40.5%), B-R (n=436, 24.4%), and ibrutinib monotherapy (n=199, 11.1%). Overall, patients had a median (IQR) age of 57 (52-62) years, and 59.4% were male. Most patients were commercially or self- insured (57.5% and 33.6%, respectively). Patients had a median Charlson Comorbidity Index (CCI) of 0 (IQR 0-1; mean [SD] 0.9 [1.4]), with the most common CCI components being diabetes (15.7%), chronic pulmonary disease (12.8%), and congestive heart failure (9.5%). During the follow-up period (median [IQR] 22.5 [10.5-35.3] months), in addition to the MCL regimen(s), patients received radiation therapy (17.4%), SCT (10.0%), and/or immunotherapy (0.2%). The use of targeted therapies (i.e. lenalidomide, bortezomib) other than ibrutinib was infrequent. When considering treatment lines, R-CHOP was the most commonly observed first regimen, followed by rituximab, B-R, and ibrutinib; for the second and third observed regimens, rituximab was the most common, followed by ibrutinib (Figure 1). The median (IQR) duration for the first observed regimen was 8.1 (3.9-18.0) months for ibrutinib, 5.0 (3.3-5.6) months for B-R, 4.0 (2.5-4.4) months for R-CHOP, and 1.9 (1.7-4.4) months for rituximab; ibrutinib also had the longest duration in the second and third line (median [IQR] 5.5 [2.4-13.5] months and 8.3 [3.9-12.4] months, respectively). Conclusion This is the largest study of MCL patients describing treatment patterns in current clinical practice among commercially insured patients. MCL patients were most commonly treated with chemoimmunotherapy for all treatment lines while ibrutinib was the second most common LOT2 and LOT3 regimen. As the treatment landscape and clinical practice continues to change with the use of novel agents, future studies are warranted to further study toxicities and outcomes in the real-world setting. Disclosures Kabadi: AstraZeneca: Employment. Burudpakdee:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Near:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Wada:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Mato:TG Therapeutics: Research Funding; Sunesis: Honoraria, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Prime Oncology: Speakers Bureau; Abbvie: Consultancy.

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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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Real-World Efficacy of Venetoclax-Based Regimens in Patients with Chronic Lymphocytic Leukemia in Israel: A Multicenter Prospective Study

Blood ◽

10.1182/blood-2021-146504 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3727-3727

Author(s):

Yair Herishanu ◽

Neta Goldschmidt ◽

Gilad Itchaki ◽

Itai Levi ◽

Ariel Aviv ◽

...

Keyword(s):

Real World ◽

Interim Analysis ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

Publicly Traded ◽

Phase Iii Clinical Trials ◽

Medical Centers ◽

Grade 3

Abstract Background: The BCL-2 inhibitor venetoclax in combination with an anti-CD20 monoclonal antibody (rituximab or obinutuzumab) has demonstrated superior outcomes and manageable safety as compared to chemo-immunotherapy in phase III clinical trials for chronic lymphocytic leukemia (CLL). Moreover, venetoclax-based regimens induced high rates of undetectable minimal residual disease (uMRD). Prospective data on the effectiveness of venetoclax-based regimens specifically with regard to achieving uMRD in a real-world setting are still lacking. Here we report the first interim analysis for efficacy and safety of an ongoing nationwide real-world study of venetoclax based therapy for CLL/small lymphocytic lymphoma (SLL). Method: A prospective observational nationwide multicenter study. Treatment-naïve (TN) and relapsed/refractory (R/R) CLL/SLL patients were enrolled in 13 medical centers in Israel. The primary endpoint was clinical response, per physician assessment 12-months after the initiation of venetoclax treatment. Key secondary endpoints included progression free survival (PFS), overall survival (OS) and uMRD as assessed at a central laboratory by 8-color flow-cytometry. Results: Between February 10, 2019, and Jun 17, 2021 (data cut), 199 CLL/SLL patients were enrolled from 13 medical centers in Israel to receive venetoclax based therapy. The study included 83 TN and 116 R/R evaluable CLL/SLL patients with a median age of 69 years (range, 34-85) and 70.5 years (range, 25-91), respectively (Table 1). R/R patients had received a median of one prior therapy with a range up to 8, of these patients 60 (51.7%) were previously treated with a B-cell receptor inhibitor (BCRi) including ibrutinib in 52 (44.8%) and idelalisib in combination with rituximab in 6 (5.2%). TN patients had been treated with venetoclax in combination with obinutuzumab (92.8%) or rituximab (4.8%) and R/R patients received either venetoclax with rituximab (60.3%) or obinutuzumab (9.5%), venetoclax monotherapy (25.8%) or triple therapy with venetoclax, rituximab and ibrutinib in 5 (4.3%). Dose escalation of venetoclax to the recommended dose of 400 mg daily was achieved in 80.7% (n=67) of TN and 81% (n=94) of R/R patients. The median duration of ramp-up was 38 and 42 days in TN and R\R patients, respectively. Prior to therapy, tumor lysis syndrome (TLS) risk was considered high in 12% and 29.3% of TN and R/R patients, respectively (Table 1). Laboratory TLS occurred in one TN patient and 4 R/R patients, whereas 3 of the R/R patients experienced clinical TLS. Nineteen TN and 75 R/R patients had a follow-up of at least 12 months or discontinued study prematurely. The 12-month overall response rate (ORR) for TN and R/R patients was 89.5% [complete response (CR) 13 (68.4%), partial response (PR) 4 (21.1%)] and 73.3% [CR 37 (49.3%), PR 18 (24%)], respectively. In the R/R cohort, the 12-month ORR among assessed patients was 67.6% (25/37) in BCRi-exposed versus 85.7% (30/35) in BCRi-naïve patients. At 12 months, peripheral blood uMRD (<0.01%) was achieved in 12 out of 14 (85.7%) TN and 26 out of 38 (68.4%) R/R evaluated patients. At a median follow-up of 5.1 months (range, 0.5-15.6) for TN and 10.1 months (range, 0-25.7) for R/R patients, the median PFS and OS, for both cohorts have not been reached. The estimated 12-month PFS was 90.9% for TN and 81.1% for R/R patients. For R/R patients with prior exposure to BCRi, the estimated 12-month PFS was 69.6% versus 94.8% in BCRi-naïve patients (figure 1). Grade ≥3 adverse events (AEs) were reported in 34.9% of TN patients and 43.9% R/R patients. The most frequent grade ≥3 AEs documented were neutropenia (TN: 19.2% and R/R 17.2%), infections (TN: 4.8% and R/R: 21.5%) and febrile neutropenia (TN: 2.4% and in R/R: 2.6%). COVID-19 occurred in 7 patients including one death. At the time of data cut, 10 deaths occurred, one TN and 9 R/R patients. Causes for death included infections (5 patients), disease progression (2 patients), acute myeloid leukemia/ myelodysplastic syndrome (2 patients) and a soft-tissue sarcoma (1 patient). Conclusions: This first interim analysis of our ongoing prospective real-world study of venetoclax-based treatment for TN and R/R CLL/SLL, demonstrates high efficacy together with a high proportion of undetectable MRD levels and a favorable toxicity profile. These efficacy results are comparable to those reported in previous Phase III clinical trials for CLL, with no new safety signals. Figure 1 Figure 1. Disclosures Herishanu: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; AstraZeneca: Honoraria. Goldschmidt: AbbVie: Consultancy, Research Funding. Itchaki: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Levi: AbbVie: Consultancy, Research Funding. Aviv: AbbVie: Honoraria, Research Funding. Fineman: AbbVie: Research Funding. Dally: AbbVie: Honoraria, Research Funding. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Abadi: AbbVie: Honoraria, Research Funding. Shvidel: AbbVie: Honoraria, Research Funding. Braester: AbbVie: Honoraria, Research Funding. Cohen: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Benjamini: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding.

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Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients Enrolled in CPX-351-301, a Randomized Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, High-Risk and/or Secondary AML

Blood ◽

10.1182/blood-2020-136882 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 44-45

Author(s):

Geoffrey L Uy ◽

Laura F. Newell ◽

Tara Lin ◽

Stuart L. Goldberg ◽

Matthew J. Wieduwilt ◽

...

Keyword(s):

Older Adults ◽

High Risk ◽

Research Funding ◽

Hematopoietic Cell Transplantation ◽

Newly Diagnosed ◽

Publicly Traded ◽

Phase 3 ◽

Secondary Aml ◽

Donor Type

Background: CPX-351 is a liposomal encapsulation of daunorubicin and cytarabine in a 1:5 molar ratio. In a randomized phase 3 study (CPX-351-301) conducted in older adults (60 to 75 years old) with newly diagnosed, high-risk and/or secondary AML, CPX-351 induction therapy was superior to standard 7+3 with improved rates of complete remission (CR) and overall survival (OS). In both older adults and high-risk AML, allogeneic hematopoietic cell transplantation (HCT) is frequently the preferred post-remission strategy owing to the high rates of relapse and poor overall survival with conventional chemotherapy approaches. After a median follow-up of 20.7 months, the primary pre-planned analysis found that more patients randomized to CPX-351 underwent HCT and an exploratory landmark survival analysis from the time of HCT favored CPX-351 (HR = 0.46 [95% CI: 0.24, 0.89]; one-sided P = 0.009). However, the initial protocol did not collect data related to HCT and the basis for improved HCT outcomes with CPX-351 was previously unknown. Here we present a detailed analysis of HCT outcomes in patients enrolled in the CPX-351-301 study with 5-years of follow-up. Methods: Patients age 60 to 75 years with high-risk and/or secondary AML were randomized in a 1:1 fashion to receive CPX-351 or 7+3 as induction and consolidation chemotherapy (Lancet J et al, JCO 2018). The protocol was amended to collect additional HCT-specific information, including donor and HCT characteristics and post-HCT outcomes, including rates of relapse and GVHD. Post-HCT outcomes including relapse, GVHD, and death were analyzed as competing events. Results: Of 309 randomized patients in the CPX-351-301 study, more patients achieved CR/CRi with CPX-351 vs 7+3 (48% vs 33%) allowing more patients to proceed to HCT (35% vs 25%) and more patients to proceed to HCT in remission (CPX-351: 41/73 [56%]; 7+3: 24/52 [46%]). The median age was 66 years with CPX-351 vs 65 years with standard induction among the transplanted cohorts; 16 patients in the CPX-351 transplanted arm were over the age of 70 compared to only 6 in the 7+3 arm. Other pre-HCT patient characteristics were balanced between the CPX-351 and 7+3 groups, including ECOG performance status (8% vs 5% with ECOG PS of 2), HCT-CI (median 4 vs 3), donor type (matched unrelated donor 49% vs 49%), and conditioning regimen intensity (myeloablative [17% vs 13%] vs reduced-intensity conditioning [43% vs 46%]). The Kaplan-Meier-estimated 3-year survival rate among transplanted patients was 56% with CPX-351 vs 23% with 7+3 (Figure 1A). The differences in survival consistently favored CPX-351 across patient age, AML subtype, disease status, donor type, and conditioning intensity (Figure 1B). Differences in OS were driven by a large reduction in non-relapse mortality (HR = 0.42 [95% CI: 0.21, 0.86]; Figure 1D). The cumulative incidence of acute GVHD with death as a competing event at 6 months from HCT date was 0.49 (95% CI: 0.35, 0.62) in the CPX-351 arm and 0.38 (95% CI: 0.23, 0.53) in the 7+3 arm. Conclusions: Analysis of HCT outcomes in patients enrolled in the CPX-351-301 study demonstrated that treatment with CPX-351 in older adults with high-risk and/or secondary AML resulted in more patients bridged to HCT and more patients transplanted in CR/CRi compared to 7+3, with improved OS in transplanted patients. The pattern of HCT outcomes suggests improved disease control with CPX-351 induction allowing higher HCT rates, but more importantly improved tolerability with less non-relapse mortality; this data supports the development of CPX-351 in other high-risk AML populations in which allogeneic HCT is the preferred post-remission strategy. Figure Disclosures Uy: Genentech: Consultancy; Agios: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas Pharma: Honoraria; Jazz Pharmaceuticals: Consultancy. Lin:Abbvie: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Prescient Therapeutics: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Ono Pharmaceutical: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Gilead Sciences: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding. Wieduwilt:Reata Pharmaceuticals: Current equity holder in publicly-traded company; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Merck: Research Funding; Leadiant: Research Funding; Amgen: Research Funding; Macrogeneics: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

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Real-World Characteristics of Patients with Peripheral T-Cell Lymphoma Receiving Frontline Brentuximab Vedotin with Chemotherapy: A Retrospective Analysis with Propensity Score Matching

Blood ◽

10.1182/blood-2020-140832 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-19

Author(s):

John M. Burke ◽

Nicholas Liu ◽

Kristina Yu-Isenberg ◽

Michelle A. Fanale ◽

Andy Surinach ◽

...

Keyword(s):

T Cell ◽

Real World ◽

Research Funding ◽

Cell Lymphoma ◽

Primary Prophylaxis ◽

Brentuximab Vedotin ◽

Publicly Traded ◽

Genetics Research ◽

T Cell Lymphomas

Introduction: In the phase 3 ECHELON-2 study (NCT01777152), treatment with brentuximab vedotin (BV) + cyclophosphamide, doxorubicin, and prednisone (A+CHP) demonstrated significantly longer progression-free and overall survival compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the frontline (FL) treatment of patients with systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL). This study supported the November 2018 US FDA approval of A+CHP as FL therapy for adults with sALCL or other CD30-expressing PTCL. The current analysis describes patient characteristics, PTCL subtypes, and supportive care use of FL A+CHP and CHOP outside of the clinical trial setting in the US. Methods: Using medical and pharmacy claims data in the Symphony Health Solutions database, a retrospective cohort analysis of patients with PTCL treated with FL A+CHP or CHOP was conducted to compare treatment and utilization characteristics. Patients ≥18 years with 1 inpatient or 2 outpatient ICD-9/10 PTCL diagnosis codes, newly initiated on A+CHP or CHOP (index date) between November 2018 and January 2020, and with ≥6 months continuous activity before and ≥3 months after the index date were included. To adjust for confounding factors, a 1:1 propensity score matching analysis was performed based on age, gender, baseline comorbidities, geographic region and length of follow-up. Results: A total of 755 patients met inclusion criteria (335 A+CHP; 420 CHOP) with a median follow-up period of 10.1 and 10.6 months, respectively. In the unmatched cohorts, 61% were male, and median age at index was 62 and 69 years for A+CHP and CHOP, respectively. The prevalence of comorbidities based on the Charlson Comorbidity Index was similar between the cohorts; prevalent conditions included diabetes, chronic pulmonary disease, congestive heart failure, and liver disease (Table 1). PTCL subtypes treated with A+CHP included sALCL (54%), PTCL-not otherwise specified (NOS; 27%), and angioimmunoblastic T-cell lymphoma (AITL; 13%); subtypes treated with CHOP included PTCL-NOS (35%), adult T-cell leukemia/lymphoma (ATLL; 35%), and AITL (11%) (Table 2). After matching, the proportion of patients who received granulocyte-colony stimulating factor (G-CSF; A+CHP: 91%, CHOP: 86%, p=0.1) and the incidence rate of neutropenia (A+CHP: 45%, CHOP: 42%, p=0.4) during FL treatment for both study cohorts was similar. Of patients who received G-CSF, the majority received it as primary prophylaxis given within the first 5 days of FL treatment initiation (A+CHP: 89%, CHOP: 85%, p=0.2). The rate of subsequent therapy (ie, therapy change after FL), was similar between A+CHP and CHOP (18% vs 21%; p=0.3) and for the sALCL subtype (16% vs 26%, p=0.2). Of the A+CHP patients who received subsequent therapy, 32% were retreated with a BV-containing regimen and 19% of CHOP patients received a BV-containing regimen. Conclusions: In this real-world analysis, US patients with PTCL newly initiated on A+CHP or CHOP were older (67 vs 58 years) than those in ECHELON-2. There was a high comorbidity burden; over half of the patients in both cohorts had 1+ comorbidities, a potential reflection of the older population. As would be expected due to a high rate of CD30-positivity in the disease, A+CHP was more commonly used than CHOP in sALCL. In PTCL subtypes in which CD30 is more variably expressed, A+CHP and CHOP were used with similar frequencies. Although clinical trials in ATLL have demonstrated improved outcomes with more complex and intensive regimens than CHOP, CHOP remains commonly used in ATLL. A+CHP was also used in PTCL subtypes not included in ECHELON-2, such as NK/T cell lymphomas. G-CSF was used as primary prophylaxis in the large majority of patients in both cohorts. The use of a BV-containing regimen as subsequent therapy was more common in A+CHP vs CHOP, probably because the tumors of A+CHP patients were more likely to have expressed CD30. Confounding by unmeasured characteristics cannot be ruled out due to inherent limitations in claims data (eg, lack of disease stage, CD30 testing and response outcomes). Characteristics and management of this real-world population with PTCL differed from those in the ECHELON-2 trial, demonstrating the importance of retrospective studies to assess the impact of new regimens on clinical practice and to identify areas for further education of practitioners. Disclosures Burke: Seattle Genetics: Speakers Bureau; Gilead: Consultancy; Bristol Myers Squibb: Consultancy; Roche: Consultancy; Epizyme: Consultancy; Adaptive: Consultancy; Kura: Consultancy; Morphosys: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Verastem: Consultancy; Astra Zeneca: Consultancy; Bayer: Consultancy; AbbVie: Consultancy. Liu:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Yu-Isenberg:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Fanale:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Surinach:Seattle Genetics: Research Funding. Flores:Seattle Genetics: Research Funding. Lisano:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Phillips:Beigene: Consultancy; AstraZeneca: Consultancy; Karyopharm: Consultancy; Bayer: Consultancy, Research Funding; Lymphoma Connect: Other; Incyte: Consultancy, Research Funding; Cardinal Health: Consultancy; University of Michigan: Current Employment; Pharmacyclics: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; BMS: Consultancy; Seattle Genetics: 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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Unmet Medical Need Among Elderly Patients with Previously Untreated DLBCL Characterized Using Real-World Data in the United States

Blood ◽

10.1182/blood-2020-136271 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-8 ◽

Cited By ~ 1

Author(s):

Ashwini Shewade ◽

Adam J Olszewski ◽

Nelson Pace ◽

Andy Surinach ◽

Gila Sellam ◽

...

Keyword(s):

Elderly Patients ◽

Real World ◽

Research Funding ◽

Publicly Traded ◽

Real World Data ◽

World Data ◽

Reduced Dose ◽

The Past ◽

Medical Need

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a significant source of cancer morbidity and mortality. More than half of all newly diagnosed patients are older than 65 years, among whom the 5-year relative survival rate is 54% (SEER 2020). Prior research has shown that not all elderly patients (≥80 years old) receive R-CHOP or mini-R-CHOP regimens as the first line of therapy (LoT); those who do not may have suboptimal outcomes (Williams, et al. Cancer 2015; Hamlin, et al. Oncologist 2014; Juul, et al. Eur J Cancer 2018). This study leverages two real-world data (RWD) sources, Flatiron Health (FH) electronic health record-derived de-identified database and SEER-Medicare (SEER-M) to characterize elderly patients with DLBCL (including observed treatment patterns), summarize overall survival (OS) outcomes, and identify unmet medical needs in this population. Methods: RWD from FH included patients with a DLBCL diagnosis on or after January 1, 2011, with follow-up until May 31, 2020. The SEER-M database is a linkage of two population-based RWD sources: the SEER Cancer Registry and Medicare claims database. RWD from SEER-M for this study included patients with a DLBCL diagnosis between January 1, 2011 and December 31, 2015, with follow-up until December 31, 2016. All fee-for-service Medicare enrollees in SEER-M had to have complete claims. RWD for basic demographics, treatments and outcomes were analyzed from both datasets; FH's database included data on certain clinical characteristics including granularity for dosing data when available, in comparison to SEER-M. This descriptive analysis included patients who were aged ≥80 years at diagnosis. Among patients in the FH database who received R-CHOP as first LoT and had available dosing data, those who received <80% of standard full doses for cyclophosphamide (750mg/m2) and doxorubicin (50mg/m2) at first administration were classified as "reduced-dose" R-CHOP. OS data were summarized using an unadjusted Kaplan-Meier survival function and 95% confidence intervals (CI). Results: The study included 725 patients from the FH database and 2613 patients from the SEER-M database; patient characteristics and outcomes were generally consistent between the two datasets. In total, 16% and 35% of the elderly patients had no record of systemic treatment in FH and SEER-M respectively (Table). More than half of the treated patients received R-CHOP in the first LoT (63% and 53% in FH and SEER-M, respectively); other patients received attenuated regimens, including rituximab plus bendamustine (R-Benda), rituximab plus cyclophosphamide, vincristine and prednisolone (R-CVP), and rituximab (R) monotherapy. Patients who received R-CHOP in the first LoT had numerically longer median OS (Flatiron: 55.0 months [95% CI: 41.8-NA]; SEER-M: 50.7 months [95% CI: 45.9-62.9]) compared with those who received other regimens (Figure A, B). Untreated patients had a median survival of 3.1 months (95% CI: 2.3-5.2) in the Flatiron dataset and 2.0 months (95% CI: 1.8-2.2) in the SEER-M dataset. Among those who received R-CHOP and with available dosing data, 51% received reduced-dose R-CHOP in the first LoT and OS appeared shorter than for patients who received full-dose R-CHOP (Figure C). Conclusions: Despite differences between the databases, RWD in FH and SEER-M both demonstrate considerable variation in the regimens received by elderly DLBCL patients, with 16-35% receiving no treatment and >50% receiving attenuated regimens including reduced-dose R-CHOP. Patients receiving regimens other than R-CHOP had a numerically lower survival probability compared with the standard of care (SoC) R-CHOP/reduced-dose R-CHOP. These data show a high unmet medical need among elderly patients with DLBCL who may not be able to tolerate immunochemotherapy regimens that have been evaluated in trials for a carefully selected patient population. Further research will aim to assess prognostic factors at the time of treatment initiation, as well as gather information on comorbidities and other factors that may prevent elderly patients from receiving SoC R-CHOP; these patients may be candidates for better-tolerated novel approaches. Disclosures Shewade: Genentech, Inc.: Current Employment. Olszewski:TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding. Pace:Genentech, Inc.: Current Employment; Exponent: Ended employment in the past 24 months; Prior employer was a consulting firm. No expert testimony given. No relevant consulting work done.: Consultancy. Surinach:Seattle Genetics: Research Funding. Sellam:F. Hoffmann-La Roche: Current Employment. Mueller:Genentech, Inc.: Current Employment, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company.

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