Racial Disparities in Telemedicine Uptake during the COVID-19 Pandemic Among Patients with Hematologic Malignancies in the United States

Abstract Background/objectives: The COVID-19 pandemic impacted healthcare visit trends, propelling healthcare systems to reduce in-person visits and hospital admissions and increasingly rely on telemedicine; whether there are differences in these trends across racial groups is unknown. This study investigated potential racial disparities in visits during the pandemic for patients with documented active treatment for hematologic malignancies. Methods: We used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to select patients with confirmed diagnosis of AML, DLBCL, FL, MCL, CLL or MM, at least 18 years old at initial diagnosis, and documented race in the EHR as Black/African American or White were included. Patients were categorized into treatment types within lines of therapy: Orals (orals + outpatient infusions with orals) vs. Inpatient treatments (chemotherapy, hematopoietic transplants & CAR-T cell therapy). Monthly visit rates were calculated as the number of visits (telemedicine or in-person [in-clinic treatment administration, vitals, and/or labs]) per active patient per 30-day standardized month, except for months in which the patient was considered not active (e.g. no documented therapy, surveillance). We used time-series forecasting methods on pre-pandemic monthly visit rate data (March 2016 - February 2020) to estimate projected counterfactual monthly visit rates (expected rates if the pandemic did not occur) between March 2020 - February 2021 for all diseases combined, for each disease, each treatment type, and each race. Differences between projected and actual monthly visit rates during the pandemic period were considered significant and related due to the pandemic if the actual visit rate was outside of the 95% prediction interval (PI) surrounding the projected estimate. We used cross-correlation analysis to test for significant differences in visit rates between Black and White patients. Results: The analysis included 17,621 patients (2,225 Black, 15,396 White): 3,041 AML, 2,715 DLBCL, 1,558 FL, 1,511 MCL, 3,813 CLL and 5,244 MM (1,166 Black, 4078 White). Across all diseases and treatment categories, Black patients had no significant reductions in in-person visit rates throughout the pandemic period compared to the projected rates. There was, however, an 18% statistically significant reduction (95% PI 9.9% - 25%) in in-person visit rates for White patients on orals during early pandemic months (March - May 2020) from a projected visit rate of 2.0 (95% PI 1.8 - 2.2) visits per patient per month to an actual visit rate of 1.61. There was no significant reduction in in-person visit rates for White patients on inpatient treatments. Telemedicine uptake was significantly higher for White patients compared with Black patients for all diseases combined across all treatment categories (Figure A & B) (t = 9.5, p < 0.01), AML inpatient treatments (t = 2.4, p = 0.04), MM orals (Figure C) (t = 6.0, p < 0.01) and MM inpatient treatments (Figure D) (t = 2.3, p = 0.04). Conclusions: A tradeoff in reductions in in-person visits and uptake of telemedicine use was observed overall. White patients had significantly higher telemedicine uptake compared with Black patients for both oral and inpatient treatments. In-person visit rates for Black patients were unchanged regardless of treatment category. These in-person visit rates reflect documented telemedicine use disparities, which requires further study into possible compound causes, including economic and societal factors. Figure. Trends over time in telemedicine visit rates for White patients (blue line) and Black patients (black line) Figure 1 Figure 1. Disclosures Neparidze: Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding; Janssen: Research Funding. Lau: Flatiron Health Inc: Current Employment; Roche: Current equity holder in publicly-traded company. Wang: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company. Davidoff: Amgen: Consultancy; AbbVie: Other: Family member consultancy. Huntington: Bayer: Honoraria; Servier: Consultancy; Pharmacyclics: Consultancy, Honoraria; Thyme Inc: Consultancy; Genentech: Consultancy; AbbVie: Consultancy; SeaGen: Consultancy; Celgene: Consultancy, Research Funding; Flatiron Health Inc.: Consultancy; DTRM Biopharm: Research Funding; TG Therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria; Novartis: Consultancy. Calip: Flatiron Health Inc: Current Employment; Roche: Current equity holder in publicly-traded company; Pfizer: Research Funding. Shah: AstraZeneca: Research Funding; Seattle Genetics: Research Funding; Epizyme: Research Funding. Stephens: Adaptive: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Abbvie: Consultancy; CSL Behring: Consultancy; Novartis: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; JUNO: Research Funding; Mingsight: Research Funding; AstraZeneca: Consultancy; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Arqule: Research Funding. Miksad: Flatiron Health Inc: Current Employment, Current holder of individual stocks in a privately-held company; Roche: Current equity holder in publicly-traded company. Parikh: Onc.AI: Current holder of individual stocks in a privately-held company; Humana: Honoraria, Research Funding; Flatiron Health Inc: Honoraria; Thyme Care: Honoraria; Nanology: Honoraria; GNS Healthcare: Current holder of individual stocks in a privately-held company. Takvorian: Genentech: Consultancy; Pfizer: Research Funding. Seymour: Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Current equity holder in publicly-traded company; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Flatiron Health Inc: Current Employment; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Impact of the COVID-19 Pandemic on in-Person Visit Rates Among Patients with Hematologic Malignancies in the United States

Blood ◽

10.1182/blood-2021-153625 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1930-1930

Author(s):

Gaurav Goyal ◽

Krystal W. Lau ◽

Xiaoliang Wang ◽

Amy J. Davidoff ◽

Scott F. Huntington ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Hematologic Malignancies ◽

Publicly Traded ◽

Advisory Committees ◽

Visit Rate ◽

Line Of Therapy ◽

Monthly Visit ◽

All Diseases ◽

Privately Held

Abstract Background/objectives: The COVID-19 pandemic led to a dramatic reduction of in-person medical care in the general population; however, impacts have not been well-characterized for patients with hematologic malignancies. This study assessed the impact of COVID-19 on healthcare delivery for patients with hematologic malignancies with documented active treatment. Methods: Patients from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database with confirmed diagnosis of AML, DLBCL, FL, MCL, CLL or MM, and age ≥ 18 years at initial diagnosis were included. To be included in the study, documented receipt of at least one systemic, non-maintenance line of therapy between March 1, 2016 - February 28, 2021 was required. Patients were categorized into treatment types within lines of therapy: Oral therapy (OralTx); outpatient infusions (OutPtTx); and inpatient infusions, including hematopoietic transplants and CAR-T cell therapy (InPtTx). Monthly visit rates were calculated as the number of visits (telemedicine or in-person [in-clinic treatment administration, vitals, and/or labs]) per active patient per 30-day standardized month. Only visits occurring within a line of therapy were included (i.e. during active therapy, excluding surveillance). Telemedicine was only available for abstraction during the pandemic period. We used time-series forecasting methods on pre-pandemic monthly visit rate data (March 2016 - February 2020) to estimate projected counterfactual visit rates between March 2020 - February 2021 (expected in-person visit rates if the pandemic had not occurred) for all diseases combined, each disease, and each treatment type. Differences between projected and actual monthly visit rates during the pandemic period were considered statistically significant and related to the pandemic if the actual visit rate was outside of the 95% prediction interval (PI) surrounding the projected estimate. Results: A total of 22,559 patients were included in this analysis (6,241 OralTx, 14,501 OutPtTx, 7,675 InPtTx): 4,069 AML, 3,641 DLBCL, 2,004 FL, 1,899 MCL, 4,574 CLL and 6,701 MM. There was a gradual downward trend in in-person visit rates across all diseases over the study period (March 2016 - February 2021, Figure) and general visit frequencies were lower for OralTx and higher for OutPtTx and InPtTx overall. For all diseases combined, early pandemic months (March - May 2020) saw an 18% (95% PI 8.9% - 25%) reduction in in-person visit rates averaged across OralTx and OutPtTx, with the projected rate being 1.5 (95% PI 1.3 - 1.6) visits per patient per month, compared to an actual rate of 1.2. Reductions in the in-person visit rates were significant for all 3 treatment types for MM, for OralTx for CLL, and for OutPtTx for MCL and CLL. Telemedicine visit rates were greatest for patients who received OralTx, followed by OutPtTx, then InPtTx, with greater use in the early pandemic months and subsequent decrease in later months. All in-person visit rates increased close to predicted rates in the later half of the pandemic period. Conclusions: In treatment of hematologic malignancies, overall documented in-person visit rates for patients on OralTx and OutPtTx significantly decreased during early pandemic months, but returned close to the projected rates later in the pandemic. There were no significant reductions in the overall in-person visit rate for patients on InPtTx. Variability in these trends by disease type was observed, with significant reductions in in-person visits impacting MM, CLL, and MCL. Figure. Visit rates over time according to treatment category Figure 1 Figure 1. Disclosures Lau: Roche: Current equity holder in publicly-traded company; Flatiron Health Inc: Current Employment. Wang: Roche: Current equity holder in publicly-traded company; Flatiron Health: Current Employment. Davidoff: AbbVie: Other: Family member consultancy; Amgen: Consultancy. Huntington: Bayer: Honoraria; Thyme Inc: Consultancy; Novartis: Consultancy; Flatiron Health Inc.: Consultancy; Genentech: Consultancy; SeaGen: Consultancy; Servier: Consultancy; AstraZeneca: Consultancy, Honoraria; TG Therapeutics: Research Funding; DTRM Biopharm: Research Funding; AbbVie: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding. Calip: Pfizer: Research Funding; Roche: Current equity holder in publicly-traded company; Flatiron Health Inc: Current Employment. Shah: AstraZeneca: Research Funding; Seattle Genetics: Research Funding; Epizyme: Research Funding. Stephens: CSL Behring: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Celgene: Consultancy; JUNO: Research Funding; Mingsight: Research Funding; Abbvie: Consultancy; Arqule: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Miksad: Flatiron Health Inc: Current Employment, Current holder of individual stocks in a privately-held company; Roche: Current equity holder in publicly-traded company. Parikh: GNS Healthcare: Current holder of individual stocks in a privately-held company; Onc.AI: Current holder of individual stocks in a privately-held company; Humana: Honoraria, Research Funding; Nanology: Honoraria; Thyme Care: Honoraria; Flatiron Health Inc: Honoraria. Takvorian: Pfizer: Research Funding; Genentech: Consultancy. Neparidze: GlaxoSmithKline: Research Funding; Janssen: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees. Seymour: Flatiron Health Inc: Current Employment; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Current equity holder in publicly-traded company; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees.

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Racial and Age-Related Differences in Impacts of High-Risk Cytogenetic Abnormalities on Survival in Multiple Myeloma in a Nationwide Electronic Health Record-Derived Database

Blood ◽

10.1182/blood-2021-152774 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4121-4121

Author(s):

Gregory S Calip ◽

Mustafa S Ascha ◽

Xiaoliang Wang ◽

Amy E Pierre ◽

Kathleen Maignan ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Cytogenetic Abnormalities ◽

Age Related ◽

Black Patients ◽

Double Hit ◽

White Patients

Abstract Background: The incidence of multiple myeloma (MM) and enrichment of cytogenetic abnormalities differ significantly between racial/ethnic groups in the US, and their significance in determining myeloma progression and survival is not well understood. Whole genome sequencing has identified unique mutational signatures in MM, including an age-related process common in hyperdiploid myeloma. Our purpose was to describe racial and age-related differences in the impact of high-risk cytogenetic abnormalities (HRCAs) on survival in MM. Methods: We conducted a retrospective cohort study of adult MM patients starting first-line therapy between January 2011 and May 2021 using the nationwide Flatiron Health electronic health record-derived de-identified database. Patient-level demographic and clinical characteristics were ascertained using structured and unstructured data, curated via technology-enabled abstraction. Patients who had documented fluorescence in situ hybridization testing within 30 days prior to or 90 days following the start of first-line treatment were included. HRCAs, including gain or amplification 1q21, deletion 17p, t(4;14), t(14;16) and t(14;20), were identified and categorized as 0, 1, or 2+ HRCAs. Our outcomes of interest were real world progression free survival (rwPFS) and overall survival (rwOS). Cox proportional hazards models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI), adjusted for demographic and clinical characteristics and treatment including time-dependent receipt of autologous stem cell transplantation. Results: From a cohort of 4889 MM patients, there were 790 (16%) Black and 2995 (61%) White patients with median ages at diagnosis of 68 and 70 years, respectively. Compared to White patients, a higher proportion of Black patients had IgG M-protein (61% vs 55%) and a lower proportion had 1+ HRCAs identified (31% vs 34%). Among all racial groups, compared to patients aged <65 years (N=1771), a higher proportion of patients aged 65+ years (N=3118) had IgA M-protein (21% vs 17%) and 1+ HRCAs identified (35% vs 33%). Multivariable models showed evidence of significant statistical interaction between age and prevalence of HRCA for rwPFS (P-int: 0.02). Among White patients, having 2+ HRCAs ("double-hit MM") compared to no HRCAs was associated with worse rwPFS in both younger and older patients (<65 years: HR 2.88, 95% CI 1.93-4.32, P<0.01; 65+ years: HR 1.51, 95% CI 1.18-1.94, P<0.01). Among Black patients, associations between double-hit MM and rwPFS were attenuated and not statistically significant regardless of age (<65 years: HR 1.81, 95% CI 0.69-4.74, P=0.23; 65+ years: HR 1.61, 95% CI 0.92-2.81, P=0.09). Similarly, we also found evidence of statistical interaction between age and prevalence of HRCA for rwOS (P-int: 0.02). Among White patients, double-hit MM was significantly associated with worse rwOS but the magnitude of increased risk differed for younger (HR 3.39, 95% CI 2.24-5.14, P<0.01) and older (HR 1.61, 95% CI 1.27-2.05, P<0.01) patients. Double-hit MM was significantly associated with worse rwOS among older Black patients (HR 1.78, 95% CI 1.03-3.06, P=0.04), but not younger Black patients (HR 1.60, 95% CI 0.58-4.40, P=0.36). Conclusions: In this cohort of newly diagnosed MM patients treated in routine practice, having double-hit MM was differentially predictive of poor survival across age groups. Double-hit MM was associated with worse rwPFS and rwOS among White patients, but these trends were less consistent among Black patients. Our current understanding of cytogenetic risk stratification of MM requires further study and additional data for identifying low- and high-risk subsets of patients across different ages and racial groups. Figure. Kaplan-Meier survivor functions for rwPFS in White (Panel A) and Black (Panel B) patients by age group and number of HRCAs Figure 1 Figure 1. Disclosures Calip: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company; Pfizer: Research Funding. Ascha: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company. Wang: Roche: Current equity holder in publicly-traded company; Flatiron Health: Current Employment. Pierre: Flatiron Health, Inc: Current Employment; Roche: Current holder of stock options in a privately-held company. Maignan: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company. Wadé: Roche: Current equity holder in publicly-traded company; Flatiron Health: Current Employment. Leng: Roche: Current equity holder in publicly-traded company; Flatiron Health: Current Employment. Seymour: Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Current equity holder in publicly-traded company; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Flatiron Health Inc: Current Employment. Patel: Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Neparidze: Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding; Janssen: Research Funding.

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Racial and Ethnic Differences in Clonal Hematopoiesis, Tumor Markers, and Clinical Outcomes of Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2021-147340 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 402-402

Author(s):

Nancy Gillis ◽

Lauren C Peres ◽

Christelle M Colin-Leitzinger ◽

Mingxiang Teng ◽

Raghunandan Reddy Alugubelli ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Multivariable Analysis ◽

Age At Diagnosis ◽

Advisory Committees ◽

Black Patients ◽

Significant Difference ◽

Hispanic Patients ◽

Race Ethnicity ◽

White Patients

Abstract Background: Multiple myeloma (MM) is twice as common in Blacks compared to Non-Hispanic (NH) Whites and Hispanics. While treatment and mortality differences have been reported for Black patients with MM compared to NH White patients, there is limited data on Hispanic populations. Furthermore, the factors driving observed differences in MM presentation and treatment responses by race and ethnicity are largely unknown. We investigated demographic, clinical, and molecular features, including tumor mutations and clonal hematopoiesis (CH), in a diverse population of patients with MM to elucidate mechanisms driving clinical disparities. Methods: Patients diagnosed with MM who consented to our institutional biorepository protocol were eligible for inclusion. Demographic and clinical data were obtained from cancer registry and abstracted from electronic medical records. MM tumor cells were purified from bone marrow aspirates by CD138 affinity chromatography. DNA was isolated from tumor cells and whole blood for each patient, and whole exome sequencing (WES) data was generated. Tumor somatic mutations were characterized using paired tumor-normal (blood) WES. CH was classified based on blood-derived somatic mutations, using paired tumors and reference populations as germline comparators. Outcomes included overall survival (OS; date of diagnosis to death/last contact) and progression-free survival (PFS; 1 st-line treatment start to 1 st disease progression/death). Results: A diverse group of MM patients (n=496) were included: NH White (80%), NH Black (10%) and Hispanic (9%). NH Black and Hispanic MM patients had a younger median age at diagnosis (57 and 53 yrs, respectively) compared to NH Whites (63 yrs, p = 0.0001; Fig A). There was no statistical difference in treatment categories received by race/ethnicity. NH Black patients had a longer time to hematopoietic cell transplant (HCT; 376 days) than NH White or Hispanic patients (248 and 270 days, respectively, p = 0.011). There was an improvement in OS for NH Black (HR 0.49, 95% CI 0.30-0.81) and Hispanic (HR 0.66, 95% CI 0.37-1.18) patients compared to NH White patients, but the association was not statistically significant in Hispanics. In univariable analysis, OS was also associated with age at diagnosis, International Staging System (ISS), treatment with HCT, and treatment regimen category. In multivariable analysis, after adjusting for age, ISS, HCT, and treatment category there was no longer a statistically significant association between OS and race/ethnicity. Although a worse PFS was present among Hispanic patients (adjusted HR 1.45, 95% CI 0.99-2.13), there was no statistically significant difference in PFS by race/ethnicity. The most mutated genes in MM tumors were KRAS (24%), NRAS (17%), TP53 (11%), DIS3 (9%), and BRAF (9%) (Fig B). Genes with significantly higher tumor mutation rates in Black compared to NH White patients were SP140 (12% v 4%, p = 0.026), AUTS2 (8% v 2%, p = 0.04), and SETD2 (6% v 1%, p = 0.037). IRF4 was most commonly mutated in Hispanics (11% v 3% in NH White and 0% in Black, p = 0.019). We identified CH using WES in 60 (12%) patients. The most CH mutations were in ASXL1, DNMT3A, and TET2. There was no difference in the prevalence of CH by race/ethnicity (p=0.8). There was a statistically significant difference in OS by race/ethnicity and CH status (Fig C). For NH Black patients, CH (HR 4.36, 95% CI 1.36-14.0) and age at diagnosis (HR 1.08, 95% CI 1.03-1.14) were associated with inferior OS (Fig C). After adjusting for age in multivariable analysis, the positive association with CH status among Black patients was no longer statistically significant (HR 2.72, 95% CI 0.48-15.4). A positive, but not statistically significant, association for PFS in NH White patients with CH was also noted (adjusted HR 1.38, 95% CI 0.95-2.0). Conclusions: This is the first study to examine differences in tumor mutation profiles, CH, and treatment among different racial and ethnic groups of patients diagnosed with MM. Our data suggest that age at diagnosis, tumor mutations, and CH may all contribute to clinical disparities observed in patients with MM. Efforts to expand our cohort and incorporate additional molecular biomarkers, epidemiologic characteristics, and clinical parameters are ongoing with the ultimate goal of elucidating targetable biological mechanisms to personalize management and optimize outcomes for diverse patients diagnosed with MM. Figure 1 Figure 1. Disclosures Hampton: M2Gen: Current Employment. Blue: WebMD: Consultancy; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Siqueira Silva: AbbVie Inc.: Research Funding; Karyopharm Therapeutics Inc.: Research Funding. Baz: GlaxoSmithKline: Consultancy, Honoraria; BMS, sanofi, Karyopharm, Janssen, AbbVie: Consultancy, Research Funding; Oncopeptides: Consultancy; Merck: Research Funding. Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Shain: Janssen oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm Therapeutics Inc.: Honoraria, Research Funding; Sanofi Genzyme: Consultancy, Speakers Bureau; Novartis Pharmaceuticals Corporation: Consultancy; GlaxoSmithLine, LLC: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive Biotechnologies Corporation: Consultancy, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Patient Characteristics, Treatment Patterns and Outcomes Among Black and White Patients with Multiple Myeloma Initiating Daratumumab: A Real-World Chart Review Study

Blood ◽

10.1182/blood-2021-145941 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1965-1965

Author(s):

Shebli Atrash ◽

Philippe Thompson-Leduc ◽

Ming-Hui Tai ◽

Shuchita Kaila ◽

Kathleen Gray ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Index Date ◽

Patient Characteristics ◽

Treatment Patterns ◽

Advisory Committees ◽

New Therapies ◽

Black Patients ◽

Line Of Therapy ◽

White Patients

Abstract Background and Objective: Daratumumab, a CD38 monoclonal antibody, was approved for the treatment of multiple myeloma (MM) among previously treated patients in 2015, and among newly diagnosed patients in 2018. While the safety and efficacy of daratumumab has been well documented in clinical trials, there is limited real world information on the use and outcomes of daratumumab in patients of different races. This is of particular relevance for potential health care disparities, as evidence suggests that African American patients with MM receive new therapies later in their disease and may experience different outcomes than White patients (Blood Adv. 2019;3:2986-94, Cancer Med. 2017;6: 2876-85). Therefore, we sought to describe patient characteristics, treatment patterns and outcomes of patients with MM who received daratumumab. Results were stratified by race (i.e., Black vs. White). Methods: We conducted a retrospective chart review of patients with MM initiating daratumumab between 1/2018 and 5/2020. De-identified data were retrieved from two U.S. clinical sites, Levine Cancer Institute (Atrium Health) and Weill Cornell Medicine. Patients were included if they had a confirmed diagnosis of MM and were at least 18 years old at the time of daratumumab initiation (index date). Patients who accessed daratumumab through interventional clinical trials were excluded. Patients were followed from the index date until death, loss to follow-up, or date of chart abstraction, whichever occurred first. Patient characteristics included age, sex, body mass index, MM stage at diagnosis, cytogenetic profile as of the index date, and number of prior regimens. Treatment patterns included type and duration of daratumumab-based regimen. Treatment outcomes included treatment response (as per physician notes and guided by the International Myeloma Working Group consensus criteria) and time to next line of therapy (TTNT; the time between the index date and the initiation of the following line of therapy, censoring at the end of follow-up). All analyses were descriptive and stratified by race. Results: A total of 252 patient charts were extracted: 89 Black (35.3%) and 163 White (64.7%). Black patients were, on average, younger at diagnosis (61.7 years old vs. 67.0) and at the index date (Table 1). The proportion of females was similar across both races (Black: 44.9%, White: 46.6%), and mean body mass index was slightly higher in Black patients (28.7 vs. 26.8). Black patients had longer time between initial MM diagnosis and initiation of daratumumab (43.2 vs. 34.1 months). MM stage at diagnosis, cytogenetic profile at index, and prior regimens were similar between White and Black patients (Table 1). While unknown cytogenetics were most common for both White (45.4%) and Black (59.6%) patients, White patients (20.2%) were twice as likely as Blacks (9.0%) to have high-risk cytogenetics. Black patients received more lines of treatment prior to the initiation of daratumumab (mean 2.9 vs. 2.3), with 55.1% of Black patients receiving 3 or more prior lines. The most common regimen was daratumumab with pomalidomide and dexamethasone (DPd) for both races (Table 1), with use of DPd being particularly common (51.7%) in Black patients. Duration of treatment with daratumumab was similar across races (Table 1). Treatment response was similar across races: among patients initiating daratumumab in first, second and third line or after, respectively, overall response rate was 100.0%, 90.9% and 67.6% for Black patients and 100.0%, 82.9% and 65.4% for White patients. Among patients initiating daratumumab in third line or after, median TTNT was 12.3 months among Black patients and 10.4 months among White patients. Conclusions: Black and White patients had similar overall response rate and comparable TTNT. However, Black patients initiated daratumumab later in their treatment, with more than half of Black patients initiating daratumumab in fourth or later line of therapy, and a lower percentage of Black patients had high-risk cytogenetics, suggesting a potential discrepancy in access to new therapies for MM. These findings were observed in a relatively modest sample size, and therefore interpretation warrants caution. Future studies should investigate whether such a discrepancy in treatment access exists, potential reasons for this discrepancy, and strategies to mitigate the effect of race on access to new therapies in MM. Figure 1 Figure 1. Disclosures Atrash: GSK: Research Funding; AMGEN: Research Funding; Jansen: Research Funding, Speakers Bureau. Thompson-Leduc: Biogen: Consultancy; Novartis: Consultancy; Shire/Takeda: Consultancy; Regeneron: Consultancy; Janssen Scientific Affairs, LLC: Consultancy; BioMerieux: Consultancy; Merck: Consultancy; GlaxoSmithKline: Consultancy; BioFire Diagnostics: Consultancy. Tai: Janssen Scientific Affairs, LLC: Current Employment. Kaila: Janssen Scientific Affairs, LLC: Current Employment. Gray: Janssen Scientific Affairs, LLC: Current Employment, Current holder of individual stocks in a privately-held company. Ghelerter: Janssen Scientific Affairs, LLC: Consultancy; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; Novartis: Consultancy. Lafeuille: Pharmacyclics: Consultancy; Pfizer: Consultancy; Janssen Scientific Affairs, LLC: Consultancy; GlaxoSmithKline: Consultancy. Lefebvre: Regeneron: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Pharmacyclics: Consultancy; Janssen Scientific Affairs, LLC: Consultancy; GlaxoSmithKline: Consultancy. Rossi: Janssen Scientific Affairs, LLC: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Pomalidomide-Dexamethasone Effectiveness in t(11;14) Positive Relapsed Multiple Myeloma in Real-World Setting

Blood ◽

10.1182/blood-2021-149336 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3803-3803

Author(s):

Sudeep Karve ◽

Shaji Kumar ◽

Veronica Gonzalez De La Calle ◽

Silvia Mangiacavalli ◽

Chang-Ki Min ◽

...

Keyword(s):

Multiple Myeloma ◽

Retrospective Study ◽

Board Of Directors ◽

Real World ◽

Stock Options ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Real World Setting ◽

Privately Held

Abstract Background: Treatment of multiple myeloma (MM) commonly encompasses combination of drugs within the three drug classes including proteasome inhibitors (PIs), immunomodulators and (IMiDs), and monoclonal antibodies, both for newly diagnosed and relapsed disease. With increasing appreciation of disease heterogeneity based on underlying genetic abnormality, and demonstration of efficacy of venetoclax in patients with t(11;14) MM, the outcomes with commonly used MM regimens among the different cytogenetic subgroups are of great interest. Venetoclax, a BCL-2 inhibitor, is being studied in t(11;14) positive MM patients who have received at least two prior lines of treatment (NCT03539744; CANOVA). However, outcomes in previously treated t(11;14) MM patients using standard of care approaches in the real-world setting is limited. Patients and methods: This non-interventional, retrospective observational cohort study included patients with t(11;14) MM from the International Myeloma Working Group (IMWG) retrospective study of t(11;14) MM. From the overall cohort, patients with t(11;14) MM receiving pomalidomide + dexamethasone (PomDex) in ≥3 rd line were selected, similar to those being enrolled in the ongoing CANOVA trial. Patients were also required to have prior exposure to lenalidomide and a PI without a history of transplant within 16 weeks prior to PomDex initiation. Patients enrolled in a clinical trial were excluded. Overall best response, time to next therapy (TTNT) as a surrogate measure for progression-free survival (PFS) and overall survival (OS) were assessed after initiation of PomDex. All analyses were descriptive in nature and were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Results: Fifty-two patients who met the inclusion criteria were analyzed. Median age was 63 years, 60% were male. Patients had a median of 3 prior lines at start of PomDex, at a median of 4.3 years from diagnosis; 52% had a prior transplant. A PR or better was observed in 34% of patients with PomDex. The median TTNT for this cohort was 6.1 months and median OS was 19.2 months. Conclusion: This retrospective study of non-trial patients with t(11;14) MM provides a benchmark for newer therapies in this patient population for comparison with both venetoclax dexamethasone in the ongoing CANOVA study as well as combinations using the pomalidomide backbone. Disclosures Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company. Kumar: Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Gonzalez De La Calle: Celgene-BMS, Janssen, Amgen: Honoraria. Mangiacavalli: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria. Kastritis: Janssen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Esteves: AbbVie: Consultancy; BMS: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Delforge: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee: Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Oncopeptides: Consultancy; Adaptive: Consultancy; GSK: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Sanofi: Consultancy. Arriola: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Ross: AbbVie: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Manthena: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Durie: Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy; Amgen: Other: fees from non-CME/CE services .

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Effect of Moderate and Severe Hemophilia a on Daily Life in Children and Their Caregivers: A CHESS Paediatrics Study Analysis

Blood ◽

10.1182/blood-2020-134658 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 43-45

Author(s):

Kate Khair ◽

Francis Nissen ◽

Mariabeth Silkey ◽

Tom Burke ◽

Aijing Shang ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Disease Burden ◽

Hemophilia A ◽

Daily Life ◽

Social Activity ◽

Publicly Traded ◽

Advisory Committees ◽

Lost Work ◽

Hours Of Work

Introduction: Hemophilia A (HA) is a congenital bleeding disorder, caused by a deficiency in clotting factor VIII (FVIII) and characterized by uncontrolled bleeding and progressive joint damage. This analysis assesses the impact of disease burden on the daily life of children with hemophilia A (CwHA) and their caregivers, addressing a deficit of current research on this topic. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey in a Paediatric Population (CHESS Paediatrics) is a retrospective, burden-of-illness study in children with moderate and severe HA (defined by endogenous FVIII [IU/dL] relative to normal; moderate, 1-5%; severe, <1%) across France, Germany, Italy, Spain and the UK. CwHA were recruited and stratified by both age group (0-5 years:6-11 years:12-17 years=1:1:1) and disease severity (severe:moderate=approximately 2:1, prioritizing children with severe HA [CwSHA]). Data for this analysis were captured from physicians, children, and their caregivers. Physicians completed online case report forms for treated children, and the child and/or their caregivers completed a paper-based questionnaire utilizing 5-point Likert scales. For CwHA aged 0-7, the questionnaire was completed by the caregiver, while for CwHA aged 8-17, children and caregivers completed different sections. Hours of care provided by the caregiver and work lost by the caregiver were reported as median values due to non-normal data distribution. Informed consent was obtained for all participants. Upon review, the study was approved by the University of Chester ethical committee. Results: Data from child/caregiver questionnaires were available for 196 CwHA (moderate, 25.5%; severe, 74.5%); the majority of these children, as expected, were receiving prophylaxis (72.4%), and did not have FVIII inhibitors (89.8%; Table 1). There was a direct impact of disease burden on CwHA, particularly with regard to physical and social activities (Figure 1). Overall, it was agreed or strongly agreed by the child or caregiver that 48.0% and 57.5% of children with moderate HA (CwMHA) and CwSHA respectively, have reduced physical activity due to HA, and 46.0% and 57.5%, respectively, have reduced social activity due to HA. A total of 36.0% and 61.0% of CwMHA and CwSHA, respectively, had adapted their treatment in anticipation of physical or social activity (Table 1). Furthermore, 34.0% of CwMHA and 55.4% of CwSHA were frustrated due to their disease, and many (CwMHA, 36.0%; CwSHA, 50.7%) felt that they had missed opportunities (Figure 1). For 66.0% of CwMHA and 76.0% of CwSHA, it was reported that their daily life was compromised due to their HA. Caregivers provided a median (interquartile range [IQR]) of 19.0 (10.0-59.5) and 12.0 (5.0-20.0) hours a week of care for the hemophilia-related needs of their CwMHA (n=30) or CwSHA (n=105), respectively. Of those who responded, 17.4% (n=4/23) and 25.0% (n=20/80) of caregivers to CwMHA or CwSHA, respectively, stated they have lost work due to their caregiving duty. This was more than twice as common for caregivers in families with multiple CwHA (42.9%, n=9/21 responses) compared with those in families with one CwHA (18.5%, n=15/81 responses). Median (IQR) hours of work per week estimated to be lost were 20.0 (17.0-22.0) for caregivers of CwMHA (n=4) and 12.5 (4.50-20.0) for caregivers of CwSHA (n=20). Conclusions: In conclusion, both children and caregivers make sacrifices in their daily lives due to HA; many CwHA reported reduced physical and social activities, fewer opportunities and feelings of frustration due to their HA. Caregivers reported spending a significant number of hours caring for their child and some reported losing work due to their caring responsibilities. However, some outcomes may be limited by the small number of respondents and narrow response options, particularly those regarding the caregiver burden. Responses on the hours of work lost may be subject to selection bias, as caregivers who have lost work may be more likely to respond to this question. Additionally, as this question is targeted at caregivers in employment, it is unknown if some caregivers have left employment due to their caregiving responsibilities. According to this analysis, children/caregivers are frequently required to adapt the child's treatment before the child engages in activities. Overall, the burden of disease was similar in children with moderate and severe HA. Disclosures Khair: Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Haemnet: Membership on an entity's Board of Directors or advisory committees. Nissen:GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Silkey:Aerotek AG: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Burke:HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Aizenas:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Noone:Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees.

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To Treat or Not to Treat? Understanding Treatment Patterns in Patients with Lower-Risk Myelofibrosis at the Time of Enrollment in the MOST Study

Blood ◽

10.1182/blood-2020-134958 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 49-51

Author(s):

Rami S. Komrokji ◽

Brady L. Stein ◽

Robyn M. Scherber ◽

Patricia Kalafut ◽

Haobo Ren ◽

...

Keyword(s):

Board Of Directors ◽

Lower Risk ◽

Research Funding ◽

Symptom Burden ◽

Risk Groups ◽

Treatment Patterns ◽

Low Risk ◽

Publicly Traded ◽

Advisory Committees ◽

Therapy Initiation

Background: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by extramedullary hematopoiesis, bone marrow fibrosis, splenomegaly, constitutional symptoms, and diminished quality of life. Treatment decisions may involve a variety of factors including prognosis and symptomatology. Data regarding real-world disease and demographic factors that contribute to therapy initiation and choice in pts with lower risk MF are limited. This analysis of data from the ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) assessed whether these factors differ for lower risk pts who were treated vs untreated at enrollment. Methods: MOST is a longitudinal, noninterventional, prospective, observational study in pts with MF or essential thrombocythemia enrolled at clinical practices within the US. Pts included in the analysis (≥18 y), had low risk MF by the Dynamic International Prognostic Scoring System (DIPSS; Blood. 2010;115:1703), or intermediate-1 (INT-1) risk by age >65 y alone. Pt data were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Pt-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 233 pts with MF enrolled at 124 sites between 11/29/2016 and 03/29/2019, 205 were included in this analysis; 28 were excluded for being INT-1 risk for reasons other than age. Of the 205 pts, 85 (41.5%) were low- and 120 (58.5%) were INT-1 risk; 56.5% (48/85) and 59.2% (71/120), respectively, were being treated at enrollment. Pt characteristics are listed in Table 1A. Fewer low- vs INT-1 risk pts were JAK2 V617F or MPL positive, and more were CALR positive. The proportion of pts with palpable splenomegaly was similar for treated low- and INT-1 risk pts. In low risk pts, the proportion of pts with palpable splenomegaly was higher in untreated vs treated pts; whereas, in INT-1 risk pts, the opposite was observed (ie, lower proportion in untreated vs treated pts). Blood counts were generally similar across cohorts, except median leukocytes were lower for low risk treated pts and platelet counts were elevated in low- vs INT-1 risk pts. The proportion of pts with comorbidities was similar across cohorts, except for fewer cardiovascular comorbidities in low- vs INT-1 risk pts. Mean TSS was lower in low- vs INT-1 risk pts, but the proportion of pts with TSS ≥20 was greater in treated vs untreated pts in both low- and INT-1 risk groups. Fatigue was the most severe pt-reported symptom in all cohorts. Differences in mean TSS and individual symptom scores between risk groups were not significant (P > 0.05), except itching was worse among INT-1 risk pts (P=0.03). Physician-reported signs and symptoms were generally more frequent for untreated vs treated pts, irrespective of risk (all P > 0.05). Most low risk (69.4%) and INT-1 risk pts (61.2%) who were currently untreated at enrollment had not received any prior MF-directed treatment (Table 1B); the most common prior treatment among currently untreated pts was hydroxyurea (HU) in both risk groups. Of currently treated pts, HU was the most common MF-directed monotherapy at enrollment in low-risk pts, and ruxolitinib was most common in INT-1 risk pts. No low risk pts and few INT-1 risk pts were currently receiving >1 MF-directed therapy at enrollment. Conclusion: These real-world data from pts with MF enrolled in MOST show that a substantial proportion of both low- and INT-1 risk pts who had received treatment before enrollment were not being treated at the time of enrollment. Although watch-and-wait is a therapeutic option, the finding that many of these lower risk pts had in fact received prior therapies suggests an unmet need for effective and tolerable second-line treatment options. Treated pts had greater pt-reported symptom burden vs untreated pts, which suggests that high symptom burden may contribute to the decision for treatment. Prospective studies are needed to evaluate symptom burden change with therapy initiation. In this regard, future analyses of data from MOST are planned to assess the longitudinal evolution of the clinical characteristics, treatment patterns, and management of pts with MF. Disclosures Komrokji: Geron: Honoraria; Agios: Honoraria, Speakers Bureau; AbbVie: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau; Acceleron: Honoraria. Stein:Incyte: Research Funding; Kartos: Other: educational content presented; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; CTI Biopharma Corp: Research Funding; NS Pharma: Research Funding; ItalPharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding.

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Bleeding Complications in Patients with Cancer and COVID 19- Analysis from the COVID 19and Cancer Consortium (CCC19) Registry

Blood ◽

10.1182/blood-2021-154314 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4997-4997

Author(s):

Surbhi Shah ◽

Shuchi Gulati ◽

Ang Li ◽

Julie Fu ◽

Vaibhav Kumar ◽

...

Keyword(s):

Mechanical Ventilation ◽

Board Of Directors ◽

Stock Options ◽

Research Funding ◽

Tumor Board ◽

Bleeding Complications ◽

Advisory Committees ◽

Icu Admission ◽

Patients With Cancer ◽

Privately Held

Abstract Background : Patients (pts) with COVID-19 are reported to have increased risk of venous thromboembolism yet bleeding has been an under recognized complication. Rates of bleeding remain unexamined in all patients especially in pts with cancer and COVID-19. Aim: To estimate the incidence of bleeding complication in patients with cancer and COVID 19 Methods: The CCC19 international registry (NCT04354701) aims to investigate complications of COVID-19 in pts with cancer. Our aim was to investigate the frequency of bleeding in hospitalized adult pts with cancer andCOVID-19, enrolled between March 16, 2020 and Feb 8, 2021. The incidence of bleeding complications was captured as defined by CCC19 and included both major and non major bleeding . Associated baseline clinic-pathologic prognostic factors and outcomes such as need for mechanical ventilation, intensive care unit (ICU) admission and mortality rates were assessed Results :3849 pts met analysis inclusion criteria. Bleeding was reported in 276 (7%) pts with median age of 70years; incidence was 6.6 % in females and 7.6 % in males, 6.5% in non-Hispanic white pts, 8.2 % in non-Hispanic Black pts, and 7.8 % in Hispanic pts. 74% had solid cancer and 29% had hematologic malignancies, 33% had received anti-cancer therapy in preceding 30 days, and 8% had surgery within 4weeks. In pts taking antiplatelet or anticoagulant medications at baseline, 7.2% developed bleeding. Need for mechanical ventilation, ICU admission, 30-day mortality, and total mortality were significantly higher in those with bleeding complications compared to those without, p<0.05 Conclusion : We describe the incidence of bleeding in a large cohort of pts with cancer and COVID-19. Bleeding events were observed in those with adverse outcomes including mechanical ventilation, ICU admission, and high mortality; the overall mortality of 43% in patients with bleeding complications is especially notable. This important complication may reflect underlying COVID-19 pathophysiology as well as iatrogenic causes. Figure 1 Figure 1. Disclosures Kumar: Diagnostica Stago: Honoraria. Zon: AMAGMA AND RLZ: Consultancy, Current holder of individual stocks in a privately-held company. Byeff: Pfizer, BMS, Takeda,Teva, Merck, United health: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Nagaraj: Novartis: Research Funding. Hwang: astrazaneca,Merck,bayer, Genentech: Consultancy, Research Funding. McKay: Myovant: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calithera: Membership on an entity's Board of Directors or advisory committees; Tempus: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tempus: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Dendreon: Consultancy; Caris: Other: Serves as a molecular tumor board ; Vividion: Consultancy; Sorrento Therapeutics: Consultancy; Bayer: Research Funding. Warner: Westat, Hemonc.org: Consultancy, Current holder of stock options in a privately-held company. Connors: Pfizer: Honoraria; CSL Behring: Research Funding; Alnylam: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Abbott: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Outcomes with Interferon in Essential Thrombocythemia: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2021-145675 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3147-3147

Author(s):

Moazzam Shahzad ◽

Mamoon Ahmed ◽

Sakina Abbas ◽

Muhammad Arslan ◽

Tooba Kashif ◽

...

Keyword(s):

Systematic Review ◽

Board Of Directors ◽

Interferon Alpha ◽

Essential Thrombocythemia ◽

Research Funding ◽

Meta Analysis ◽

Molecular Response ◽

Publicly Traded ◽

Advisory Committees ◽

Hematological Response

Abstract Introduction Essential thrombocythemia (ET) is a BCR-ABL negative myeloproliferative disorder characterized by high burden of symptoms, thrombocytosis, increased risk of thrombosis and bleeding, and risk of progression to Myelofibrosis. Interferon alpha (IFN-α) is a potent immunomodulation agent proposed to be capable of inducing complete hematological remission in patients with myeloproliferative disorders. Many INF- α have been studied for treatment of patients with ET. We present a systematic review and meta-analysis assessing the efficacy of IFN-α therapy in patients with ET. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on PubMed, Cochrane, and Clinical trials.gov using MeSH terms and keywords for " Thrombocythemia, Essential " AND " Interferons " in April 2021. We did not place any time constraints. Our search produced a total of 825 records and duplicates were removed. After screening and removing irrelevant and review articles, we included 21 original articles reporting IFN-α as the only treatment for ET in adult patients. The data were collected for baseline characteristics of the participants and efficacy and safety of the intervention. Quality evaluation was done using the NIH quality assessment tool. The inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). Results A total of 388 patients from 21 articles were evaluated. The median age of participants was 54 (35-62) years and 31% (n=64/205) were males. The type of IFN used were Interferon-alpha in 4 studies, pegylated (PEG)IFN-α-2a in 2 studies, IFN-α-2b in 6 studies, recombinant IFN-α-2C in 3 studies, recombinant IFN-y in 1 study, PEG-IFN-2b in 1 study, recombinant IFN-2b in 2 studies, and PEG-IFN in 1 study. The pooled overall hematological response (OHR) was 86.4% (95% Cl 0.67-0.98, I 2= 65%, p=0.02, n=73) with complete hematological response (CHR) of 70.6% (95% Cl 0.54-0.84, I 2=34%, p=0.21, n=65) and partial hematological response (PHR) of 13% (95% Cl 0.02-0.27, I 2=42%, p=0.16, n=65). The pooled overall molecular response (OMR) was 84% (95% Cl 0.72-0.93, I 2=13%, p=<0.01, n=81) with complete molecular response (CMR) of 64.2% (95% Cl 0.41-0.84, I 2=68%, p=<0.01, n=81) and partial molecular response (PMR) of 35% (95% Cl 0.16-0.56, I 2=33%, p=0.01, n=43). Side effects reported were nausea, allergic reactions, liver dysfunction, dose dependent mild myalgia, fever, malaise, itching, persistent fever, headache, and flu like symptoms. Conclusion Interferon alpha, in different formulations shows consistent and high activity in patients with essential thrombocythemia. It resulted in clinical responses, as well as molecular responses. Side effect profiles were consistent among different reports and were reasonable tolerated. There is a large body of evidence supporting actively and safety of this approach in a diverse ET patient population. Figure 1 Figure 1. Disclosures McGuirk: Gamida Cell: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Bellicum Pharmaceuticals: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Pluristem Therapeutics: Research Funding. Yacoub: Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company.

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A Phase I Trial of the Antibody-Cytokine Fusion Protein F16IL2 in Combination with Anti-CD33 Immunotherapy for Posttransplant AML Relapse

Blood ◽

10.1182/blood-2021-145859 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2345-2345

Author(s):

Andrew F. Berdel ◽

Christoph Rollig ◽

Martin Wermke ◽

Linus Angenendt ◽

Leo Ruhnke ◽

...

Keyword(s):

Fusion Protein ◽

Nk Cells ◽

Board Of Directors ◽

Dose Escalation ◽

Research Funding ◽

Human Antibody ◽

Publicly Traded ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Dose Levels

Abstract Introduction Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but shortage of environmental growth factors and deficient recognition of malignant cells may limit their anticancer efficacy. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to the leukemia-modified extracellular matrix (ECM) would increase NK cell abundance and activity to potentiate antibody-dependent cellular cytotoxicity (ADCC) against acute myeloid leukemia (AML) blasts. In this novel-novel combination dose-escalation phase 1 trial, we enrolled patients with AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of F16IL2, an antibody-cytokine fusion protein composed of the human antibody fragment scFv(F16) in diabody format and two molecules of human IL-2, in combination with the Fc-optimized, ADCC-mediating anti-CD33 monoclonal antibody BI 836858. F16 specifically targets the A1 domain of the ECM protein tenascin C (TnC), which is spliced into the TnC molecule during active angiogenesis and tissue remodeling while it is virtually absent in normal tissues. Methods F16IL2 (10 - 20 Mio IU IV) was administered on days 1, 8, 15 and 22 of 28-day cycles, followed by administration of BI 836858 (10 - 40 mg IV) two days after each F16IL2 infusion. Dose escalation was performed over 4 dose levels (DL). Cohort 1 (10 Mio IU F16IL2 and 10 mg BI 836858, n = 5), cohort 2 (10 Mio IU F16IL2 and 20 mg BI 836858, n = 3), cohort 3 (20 Mio IU F16IL2 and 20 mg BI 836858, n = 4), cohort 4 (20 Mio IU F16IL2 and 40 mg BI 836858, n = 3). Safety and tolerability, pharmacodynamics and -kinetics, clinical efficacy and immune effector cell dynamics were investigated. This trial was registered at EudraCT as #2015-004763-37. Results Between December 2016 and March 2020, 15 patients with a median age of 50 years (range, 20 - 68) were enrolled and treated across 4 dose levels. Six patients (40%) had received two or more prior HSCT. The most frequent drug-related AEs (F16IL2 or BI 836858 or combination) were pyrexia (n = 13, 87%), chills (n = 12, 80%) and infusion-related reactions (n = 9, 60%), consistent with the expected toxicity profile of cytokine-armed or naked mAbs. These events were generally manageable, transient and of grade ≤ 2. One dose-limiting toxicity occurred at each of DL 3 (pulmonary edema) and 4 (acute GVHD). No patient died within the first 30 days of treatment initiation. Whereas no formal maximum tolerated dose (MTD) was reached, the maximum tested dose of 20 Mio IU F16IL2 and 40 mg BI 836858 was considered the recommended dose (RD). Three objective responses (1 CR, 1 CRi, 1 PR in extramedullary AML) were observed among 7 patients treated at the two higher DL, whereas no responses occurred at the two starting DL. Median OS among all 15 patients was 4.8 months (1.5 - 12.9), with a 6- and 12-month OS of 40% and 27%, respectively. Among those 7 patients whose AML was at least temporarily controlled with study treatment (CR/CRi, PR, SD), 12-month OS was 67% vs. 0% in non-responders. Combination therapy stimulated the expansion and activation of NK cells in bone marrow and peripheral blood. Conclusions To the best of our knowledge, this is the first study demonstrating that the strategy of potentiating ADCC with tumor-targeted immunocytokines is feasible in humans. In the difficult-to-treat situation of posttransplant AML relapse, responses were observed at higher DL, even in patients with extramedullary disease. The antibody-mediated targeted delivery of IL-2 to the ECM combined with anti-CD33 immunotherapy represents an innovative experimental approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. Disclosures Wermke: Novartis, Roche, Pfizer, BMS: Consultancy, Honoraria, Research Funding. Hemmerle: Philogen S.p.A.: Current Employment. Schäfers: Philogen S.p.A.: Research Funding. Rossig: BMS and Celgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; AdBoards by Amgen: Honoraria. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Rueter: Boehringer Ingelheim Pharma GmbH & Co. KG: Current Employment. Neri: Philogen S.p.A.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Multiple patents on vascular targeting; ETH Zurich: Patents & Royalties: CD117xCD3 TEA. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Schliemann: Roche: Consultancy; Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Astellas: Consultancy; Pfizer: Consultancy; BMS: Consultancy, Other: travel grants; Boehringer-Ingelheim: Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; AstraZeneca: Consultancy; Abbvie: Consultancy, Other: travel grants.

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