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

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

Blood ◽

10.1182/blood-2021-153787 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1973-1973

Author(s):

Natalia Neparidze ◽

Krystal W. Lau ◽

Xiaoliang Wang ◽

Amy J. Davidoff ◽

Scott F. Huntington ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Visit Rate ◽

Black Patients ◽

Monthly Visit ◽

All Diseases ◽

Privately Held ◽

White Patients

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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Creating a Variant Database for the American Society of Hematalogy By Consensus Variant Classification of Common Genes Associated with Hematologic Malignancies

Blood ◽

10.1182/blood-2020-141204 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-5

Author(s):

Niroshan Nadarajah ◽

Alex Wagner ◽

Rafael Bejar ◽

Mark Ewalt ◽

Annette S. Kim ◽

...

Keyword(s):

Patient Care ◽

Board Of Directors ◽

Working Group ◽

Research Funding ◽

Hematologic Malignancies ◽

Cancer Center ◽

Variant Classification ◽

Publicly Traded ◽

High Confidence ◽

Advisory Committees

Background: With the rapid decline of sequencing costs and the introduction of next-generation sequencing (NGS) instruments with higher processing capacity, the rate-limiting step in reporting genetic test results is moving away from sequencing production towards data interpretation. Powerful bioinformatics tools have been created to address this bottleneck. Though substantial advances have been made in clinical variant classification, much work remains. This is particularly true in the evaluation of somatic variants, where there is currently a high degree of variability in how members of the global molecular genetics and pathology community establish and validate bioinformatics pipelines and apply classification guidelines, and in how results are reported to clinicians. Aim: Create a reliable and widely available resource for variants relevant for hematologic malignancies and make their classification readily accessible to the wider hematology community, facilitating NGS diagnostics and improve the consistency and robustness of testing results to improve patient care . Methods: The ASH Somatic Working Group (SWG) is comprised of hematologists, hematopathologists, molecular biologists and bioinformaticians. The group was formed under the auspices of ASH two years ago to improve clarity around the various gene panels being used in our community and in the reporting of genetic variants associated with hematologic malignancies. The group collected 1) the list of genes (i.e. entity-specific panels) that are typically used in research or clinical laboratory applications at 8 different and specialized laboratories; 2) the variants within those genes and their respective internally developed tiering and interpretations among 6 laboratories; and 3) the institutional bioinformatics pipelines used for those interpretations. The working group identified 70 genes most commonly used in assays for myeloid and lymphoid diseases. A three-class system for defining somatic pathogenicity was used, to unify the submissions from 6 institutions. Pathogenic variants are those that have been clearly determined to be associated with tumorigenesis . Variants of unknown significance (VUS) may have evidence supporting or refuting their effect on somatic pathogenicity, but this evidence is not yet strong enough to classify the variants as pathogenic or benign. Benign variants have been determined not to drive tumorigenesis and are typically polymorphisms that are present throughout the (healthy) population at variable frequency. Individual variant assessment was performed by the contributing institutions using a variety of resources, including ClinVar, COSMIC, cBioPortal/OnkoKB, St. Jude PCGP, ARUP, LOVD, dbSNP and IARC databases, as well as population frequency information from gnomAD/ExAC and in-silico mutation impact prediction tools included SIFT, PolyPhen2, Mutation assessor, LRT, FATHMM, CADD, REVEL and dbNSFP. Additionally, evidence was uncovered through manual literature review. Results: Through an iterative process, the SWG has initially identified 202 variants of high confidence (with highly concordant interpretation amongst contributing laboratories) in 42 of 70 genes. These results will be publicly available as both as a multi-institutional collaborative manuscript on best practices in this field as well as a searchable web application on the ASH web site (www.hematology.org/research) to aid other clinicians and investigators. On this website variants can be queried using genomic coordinates based on hg19, GRCh38 or Gene and HGVSc nomenclature. With the ongoing process of resolving remaining discrepancies, the high-confidence data will be updated regularly, with evidence provided to support classification. Conclusions: ASH has created an application to serve as a resource for NGS diagnostics based on a systematic review process, which we anticipate will lead to more consistency in molecular testing reports for patients undergoing evaluation of myeloid and lymphoid malignancies. Regular updates will help hematology professionals to use NGS in routine patient care on an ongoing basis. Disclosures Wagner: Nationwide Children´s Hospital: Current Employment. Bejar:Genoptix/NeoGenomics: Honoraria; Forty-Seven/Gilead: Honoraria; Daiichi-Sankyo: Honoraria; Celgene/BMS: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Astex/Otsuka: Honoraria; AbbVie/Genentech: Honoraria; Aptose Biosciences: Current Employment. Ewalt:University of Colorado: Current Employment; Memorial Sloan Kettering Cancer Center: Current Employment. Kim:Brigham and Women´s Hospital: Current Employment. Le Beau:Varian Medical Systems: Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Membership on an entity's Board of Directors or advisory committees. Shammo:Onconova: Research Funding; Abbive: Current equity holder in publicly-traded company; Sanofi: Speakers Bureau; Takeda: Current equity holder in publicly-traded company; Agios: Consultancy; Novartis: Consultancy; Regeneron: Consultancy; BMS: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Apellis: Consultancy; Incyte: Consultancy, Research Funding, Speakers Bureau; Baxter: Current equity holder in publicly-traded company; Alexion: Consultancy, Research Funding, Speakers Bureau. Ryan:American Society of Hematology: Current Employment. Steensma:Aprea Therapeutics: Research Funding; Arrowhead Pharmaceuticals: Current equity holder in publicly-traded company; Astex Pharmaceuticals, Otsuka: Consultancy; H3 Biosciences: Research Funding; Takeda: Consultancy; BMS/Celgene: Consultancy; Onconova: Consultancy; Arena: Current equity holder in publicly-traded company; CRISPR: Current equity holder in publicly-traded company. Zehir:Memorial Sloan Kettering Cancer Center: Current Employment; Illumina: Honoraria.

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Seroconversion Rates after COVID-19 Vaccination Amongst Patients with Hematologic Malignancies: Results of a Rapid Vaccination and Evaluation Program in a Minority Rich, Ethnically Diverse Inner City Cohort

Blood ◽

10.1182/blood-2021-151309 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2537-2537

Author(s):

Lauren C Shapiro ◽

Radhika Gali ◽

Astha Thakkar ◽

Jesus D Gonzalez-Lugo ◽

Abdul Hamid Bazarbachi ◽

...

Keyword(s):

T Cell ◽

Board Of Directors ◽

Research Funding ◽

Hematologic Malignancies ◽

Publicly Traded ◽

Advisory Committees ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

Abstract It is well established that COVID-19 carries a higher risk of morbidity and mortality in patients (pts) with hematologic malignancies. Emerging data suggests that despite the 3 COVID-19 vaccines with emergency use authorization (EUA) by the FDA inducing high levels of immunity in the general population, pts with hematologic malignancies have lower rates of seroconversion for the SARS-CoV-2 Spike antibody (Spike IgG) and thus possibly lower protection against severe COVID-19. We established a program of rapid vaccination and evaluation of response in an inner city minority population to help determine the factors that contribute to the poor seroconversion to COVID-19 vaccination in pts with hematologic malignancies. We conducted a cross-sectional cohort study of pts with hematologic malignancies seen at Montefiore Medical Center between March 29, 2021 and July 8, 2021 who completed their vaccination series with 1 of the 3 FDA EUA COVID-19 vaccines, Moderna, Pfizer, or Johnson & Johnson (J&J). We qualitatively measured Spike IgG production in all pts using the AdviseDx Spike IgG assay and performed quantitative analysis on pts who completed their vaccination series with at least 14 days (d) after the 2 nd dose of the Moderna or Pfizer vaccines or 28d after the single J&J vaccine. Safety data was collected via questionnaires or as part of the electronic medical record. We analyzed the characteristics of these pts using standard descriptive statistics and associations between pts characteristics, cancer subtypes, treatments, and vaccine response using a Fisher Exact test, Kruskal-Wallis Rank Sum test, or Kendall Tau-b test. A total of 121 pts with hematologic malignancies were enrolled and another 10 pts were included by retrospective chart review. Five pts did not have a Spike IgG performed after consent and excluded. Ten patients had Spike IgG testing before completion of their vaccination series and excluded from quantitative analyses. A total of 116 pts were included in immunogenicity analysis and 106 pts in quantitative analysis. Baseline characteristics and representative malignancies are listed in Table 1. Seventy pts (60%) received Pfizer, 36 pts (31%) Moderna, and 10 pts (9%) J&J. Median time from vaccination completion to Spike IgG was 40d. We observed a high-rate of seropositivity (86%) with 16 pts (14%) having a negative Spike IgG. Percent positivity was not statistically significant between vaccine types (p=0.50). We observed significantly lower seroconversion rates in pts with Non-Hodgkin lymphoma (p=0.005) and pts who received: cytotoxic chemotherapy (p=0.002), IVIG (p=0.01), CAR-T cell therapy (p=0.00002), and CD20 monoclonal antibodies (Ab) (p=0.0000008) especially within 6 mo of Spike Ab evaluation (p=0.01). All pts who received anti-CD19 (Axi-cel) CAR-T therapy (0/6) were seronegative, and 1 pt that received BCMA directed CAR-T (Cilta-cel) was seropositive with no association between timing CAR-T cell infusion and seroconversion/titer. Use of BCL2 inhibitors (p=0.04), CD20 monoclonal Ab (p=0.0009), CAR-T cell therapy (p=0.01), BTK inhibitors (p=0.04), current steroid use (p=0.002), and IVIG (p=0.003) also correlated with significantly lower Ab titers with a trend toward lower Ab titers in pts on any active cancer therapy at time of vaccination (p=0.051). Immunomodulatory drugs (p=0.01) and proteasome inhibitors (p=0.01) had significantly higher seroconversion rates, and pts with history prior COVID-19 (12/106) had significantly higher Ab titers (p=0.0003). Of 47 pts who received stem cell transplant, 43 received an autologous (37 seropositive, 6 seronegative) and 4 an allogeneic transplant (3 seropositive, 1 seronegative), with no significant association with seroconversion, Ab titer, or time since transplant (greater or less than 1 year). The majority of pts, 64% and 53%, reported no adverse effects (AE) to the 1 st and 2 nd dose respectively. The most common AE were mild in severity and included sore arm, muscle aches, fatigue, and fever. No life-threatening AE were observed. Our findings indicate that vaccination is safe, effective, and well tolerated in the majority of pts with hematologic malignancies. We observed that pts receiving B-cell depleting therapies are unable to mount an effective serological response to COVID-19 vaccines and remain vulnerable to the disease. Novel immunization strategies (active or passive) are urgently needed in this population. Figure 1 Figure 1. Disclosures Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy; GLC: Consultancy. Halmos: Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mirati: Research Funding; Elevation: Research Funding; Blueprint: Research Funding; Advaxis: Research Funding; Eli-Lilly: Research Funding; TPT: Membership on an entity's Board of Directors or advisory committees; Apollomics: Membership on an entity's Board of Directors or advisory committees; Guardant Health: Membership on an entity's Board of Directors or advisory committees. Verma: BMS: Research Funding; GSK: Research Funding; Novartis: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Eli Lilly: Research Funding; Curis: Research Funding; Medpacto: Research Funding; Incyte: Research Funding; Acceleron: Consultancy; Stelexis: Current equity holder in publicly-traded company; Celgene: Consultancy; Throws Exception: Current equity holder in publicly-traded company.

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Real-World Treatment Patterns in Patients with Light Chain (AL) Amyloidosis: Analysis of the Optum US Electronic Health Records and Commercial Claims Database

Blood ◽

10.1182/blood-2020-140405 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-5

Author(s):

Angela Dispenzieri ◽

Jeff Zonder ◽

James Hoffman ◽

Sandy W. Wong ◽

Michaela Liedtke ◽

...

Keyword(s):

Board Of Directors ◽

Real World ◽

Research Funding ◽

Al Amyloidosis ◽

Cell Transplant ◽

Publicly Traded ◽

Real World Data ◽

Advisory Committees ◽

Line Of Therapy ◽

Diagnosis Date

Background: Light chain (AL) amyloidosis is a rare disease in which deposits of insoluble amyloid derived from immunoglobulin light chains accumulate and cause dysfunction of organs including the heart and kidneys. In order to reverse organ damage and improve overall survival, treatment must provide rapid, deep, and sustained hematologic responses. Although therapies approved for the treatment of multiple myeloma have demonstrated some efficacy, there are currently no health authority-approved treatments for AL amyloidosis. A retrospective observational study was undertaken to characterize patients and describe treatment patterns in patients with AL amyloidosis from real-world data in the US. Methods: Data were extracted from Optum Electronic Health Records (EHR) and Optum Clinformatics Data Mart (claims) databases. Eligible patients had (1) a diagnosis of AL amyloidosis (ICD-10 code E85.81) on or after January 1, 2008 or (2) a diagnosis of amyloidosis (ICD-9 codes 277.30, 277.39; ICD-10 codes E85.89, E85.9) on or after January 1, 2008 and at least one line of therapy (LOT) comprising one or more of the following treatments: bendamustine bortezomib, carfilzomib, cyclophosphamide, daratumumab, dexamethasone, doxorubicin, elotuzumab, etoposide, interferon alfa-2a, interferon alfa-2b, ixazomib, lenalidomide, melphalan, panobinostat, pomalidomide, prednisone/prednisolone, thalidomide, vincristine, or autologous stem cell transplant. Patients were required to have continuous medical enrollment during the 365 days prior to the index amyloidosis diagnosis date (claims data) or have first active date at least 365 days prior to index amyloidosis date (EHR data), must not have had prior cancer in the 365-day period prior to the index amyloidosis diagnosis date, and must have been age ≥18 years at time of amyloidosis diagnosis. Patients treated with dexamethasone only or dexamethasone and prednisolone only for ≤90 days and those treated with prednisone/prednisolone only irrespective of duration were excluded. LOTs were defined by a start date, an end date, and a distinct regimen made up of ≥1 drugs. Patients may have multiple sequential LOTs during the available follow-up period. Comorbidities were scored according to the Charlson Comorbidity Index (CCI). A score of 0 reflects no comorbidities; higher scores reflect increased mortality risk and the maximum score is 24. Descriptive statistics are provided for patient characteristics at index diagnosis date for patients who had ≥1 LOT, distribution of regimens in each LOT, treatment attrition, and duration of treatment in each line of therapy and by regimen. Results: Data from 1688 patients (Optum claims, n=624; Optum EHR, n=1064) were included in the analysis (Figure). Median age at diagnosis was 67 years and 55.7% of patients were male. Almost 70% of patients had an index diagnosis date between 2013 and 2019. The median CCI score at index diagnosis date (based on comorbidities in the 365-day pre-index diagnosis period) was 1 and 10.9% of patients had a stem cell transplant on or after the index diagnosis date. The three most common comorbidities were hypertension (50.8%), renal failure (26.2%), and congestive heart failure (24.6%). Median follow-up period was 28 months. Treatment information for regimens used by ≥5% of patients for LOT1 is summarized in the Table. The most common treatment regimen for LOT1 was a proteasome inhibitor (PI), an alkylating agent, and a steroid (n=392, 23.2%); this combination was used for an average of 111 days. Of patients treated with this combination, the most common regimen was bortezomib, cyclophosphamide, and dexamethasone (VCd), used by 358 patients. Steroid only (dexamethasone for ≥90 days) regimens accounted for 16.4% and a PI ± steroid for 13.2% of LOT1. A limitation of the study is that assumptions were used to classify AL amyloidosis vs other types of amyloidosis. Conclusions: VCd is the most commonly used regimen in patients with newly-diagnosed AL amyloidosis. This is consistent with clinical guidelines and real world data from Europe (Palladini et al, EHA 2020), supporting this regimen as the current standard of care for treatment of patients with newly-diagnosed AL amyloidosis. Disclosures Dispenzieri: Celgene: Research Funding; Pfizer: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Zonder:Intellia, Amgen, Takeda, Janssen, Regeneron, Alnylam, Caelum, Oncopeptides: Consultancy; BMS, Celgene: Research Funding. Hoffman:Loxo: Current equity holder in publicly-traded company; Celgene: Honoraria, Speakers Bureau. Wong:Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Fortis: Research Funding; Roche: Research Funding; GSK: Research Funding; Amgen: Consultancy; Bristol Myers Squibb: Research Funding. Liedtke:Adaptive: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Abonour:BMS: Consultancy, Research Funding; Takeda: Consultancy; Janssen: Honoraria, Research Funding; Celgene: Consultancy. D'Souza:Amgen, Merck, TenoBio: Research Funding; Akcea, Imbrium, Janssen, Pfizer: Consultancy. Lee:Janssen: Current Employment. Nair:Janssen: Current Employment. Potluri:SmartAnalyst Inc.: Current Employment. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Lam:Janssen: Current Employment. Mehra:Janssen: Current Employment.

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A First-in-Human Phase 1 Study of Oral LOXO-338, a Selective BCL2 Inhibitor, in Patients with Advanced Hematologic Malignancies (Trial in Progress)

Blood ◽

10.1182/blood-2021-145380 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2424-2424

Author(s):

Alvaro J. Alencar ◽

Lindsey E. Roeker ◽

Marc Hoffmann ◽

Guru Subramanian Guru Murthy ◽

Vishalkumar Patel ◽

...

Keyword(s):

B Cell ◽

Board Of Directors ◽

Standard Therapy ◽

Research Funding ◽

Phase 1 ◽

Hematologic Malignancies ◽

Publicly Traded ◽

Advisory Committees ◽

Molecule Inhibitor ◽

Orally Bioavailable

Abstract Background: B-cell lymphoma 2 (BCL2) is a key regulator of apoptosis and provides protection from cell death in many hematological malignancies. The BCL2 inhibitor venetoclax is approved for the treatment of CLL/SLL and acute myeloid leukemia and has activity in other lymphoid malignancies. LOXO-338 is a novel, orally bioavailable small molecule inhibitor of BCL2, designed to achieve selectivity over BCL-xL and thus avoid dose-limiting thrombocytopenia associated with BCL-xL inhibition. In preclinical studies, LOXO-338 showed a favorable pharmacological profile, selectively inhibited BCL2, and was well-tolerated in vivo. LOXO-338 also demonstrated dose-dependent tumor growth inhibition in various murine xenograft models, and showed improved efficacy in combination with pirtobrutinib, a highly selective, non-covalent BTK inhibitor (Brandhuber et al. Cancer Res 2021; 81, 13 Supplement, 1258). Study Design and Methods: LOXO-BCL-20001 is an open-label, multi-center, first-in-human Phase 1 study of oral LOXO-338 in patients with advanced hematologic malignancies who have received standard therapy. The study will be conducted in 2 parts. Part 1 will evaluate LOXO-338 as monotherapy, and will explore different dosing strategies. Part 2 will evaluate LOXO-338 in combination with pirtobrutinib. The dose escalation portion of the study in Part 1 will follow an i3+3 design. Each cycle will be 28 days (4 weeks). Eligible patients include those with CLL/SLL, mantle cell lymphoma (MCL), and Waldenstrӧm macroglobulinemia (WM) who have already received standard therapy. Patients with other B-cell non-Hodgkin lymphomas (NHLs) who failed standard therapy or, in the opinion of the investigator, have no known available options to provide benefit for the patient's condition, are also eligible. Patients must have recovered from prior treatment-related adverse events. Patients with active or suspected Richter transformation, transformed low grade lymphoma, Burkitt or Burkitt-like lymphoma, and multiple myeloma (MM) are eligible in dose-expansion. Key exclusion criteria include history of CNS involvement, stem cell transplant or CAR-T therapy <60 days, concurrent anticancer therapy, and clinically significant cardiovascular disease. The primary objective of Part 1 is to determine the maximum tolerated dose (MTD)/ recommended Phase 2 dose (RP2D) of oral LOXO-338 in patients who were previously treated for CLL/SLL and other B-cell NHLs. Key secondary objectives include determining the safety and tolerability, and pharmacokinetic properties of LOXO-338. Antitumor activity will be evaluated based on overall response rate (ORR), progression-free survival (PFS), time to progression (TTP) and duration of response (DOR) based on disease-specific response criteria per investigator assessment. Key objectives of part 2 are to determine the safety profile and tolerability, PK properties, and anti-tumor activity of LOXO-338 in combination with pirtobrutinib. Disclosures Alencar: Seattle Genetics: Consultancy; Kite Pharma: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Incyte: Consultancy; Epizyme: Consultancy; Celgene: Consultancy; BeiGene: Consultancy; Amgen: Consultancy. Roeker: AbbVie, AstraZeneca, Janssen, LOXO, Pharmacyclics, TG Therapeutics, Vaniam Group, Verastem: Consultancy; Pharmacyclics: Consultancy; Pfizer: Consultancy, Research Funding; Loxo Oncology: Consultancy; TG Therapeutics: Consultancy; Abbot Laboratories: Current equity holder in publicly-traded company. Hoffmann: TG Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmcyclics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria. Guru Murthy: Cancerexpertnow: Honoraria; Guidepoint: Consultancy; Techspert: Consultancy; Qessential: Consultancy; Cardinal Health Inc.: Honoraria; TG therapeutics: Other: Advisory board. Patel: Loxo Oncology at Lilly: Current Employment, Current equity holder in publicly-traded company. Ku: Loxo Oncology at Lilly: Current Employment, Current holder of stock options in a privately-held company. Pauff: Loxo Oncology at Lilly: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Eyre: Incyte: Consultancy; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Secura Bio: Consultancy, Honoraria; Janssen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding. Jurczak: Celtrion: Research Funding; Celgene: Research Funding; Debbiopharm: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo Oncology: Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Research Funding; Incyte: Research Funding; Merck: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. OffLabel Disclosure: LOXO-338 is a novel, orally bioavailable small molecule inhibitor of BCL2 for advanced hematologic malignancies.

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The Impact of Non-Clinical Factors in Clinical Trial Enrollments of Patients with Hematologic Malignancies

Blood ◽

10.1182/blood-2021-148135 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1914-1914

Author(s):

Jamile M. Shammo ◽

Anne Timmermann ◽

Deborah A. Katz ◽

Agne Paner ◽

Seo-Hyun Kim ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Medical Center ◽

First Language ◽

Hematologic Malignancies ◽

Clinical Factors ◽

Advisory Committees ◽

Caregiver Support ◽

Hispanic White ◽

Privately Held

Abstract Introduction The improvement of care and advancement of treatment options is heavily reliant on the success and diversity of clinical trials (CTs), yet data suggests that only 3-9% of patients with a cancer diagnosis participate in CTs. We sought to evaluate reasons for declining participation in CTs among patients with hematologic malignancies within our medical center. Our primary objective was to assess the prevalence of non-clinical factors in patients contributing to the lack of participation compared to those who agreed to participate. The secondary objective was to identify the reasons noted by patients for declining trials. Methods We conducted a retrospective chart review of adult patients with hematologic malignancies who were offered a clinical trial from 2016-2020. Eligible patients were identified through review of Cancer Center Clinical Trials Office screening logs. We collected data relative to: disease, sex, age, race and ethnicity, English as a first language, marital status, caregiver support, level of education, type of insurance, trial phase, and trial indication. The data was compared between patients who refused participation versus those who agreed to participate. Descriptive statistics, chi-square analysis, and multivariate logistic regression were used to interpret the data with IBM SPSS Statistics. Results Of patients diagnosed with hematologic malignancies and offered a CT from 2016 to 2020 at our center, 136 signed consent and 125 declined participation. The sample was predominantly older with a mean patient age of 60.9 in those who signed ICF and 61.9 in those who declined participation (Table 1). Males and non-Hispanic white patients encompassed over half of the sample in each group. Multiple myeloma was the most common diagnosis among either group. Trials offered were predominantly phase 2 or 3 and for varying disease states. We found that patients who were divorced (P = 0.024), did not have caregiver support (P = 0.005), and did not speak English as their first language (P = 0.004) were more likely to decline CT participation (Table 2). The most common reasons that patients cited for declining participation were: preference for another treatment option, distance for travel, and concerns for transportation (Table 3). Conclusion In this retrospective analysis evaluating reasons behind CT refusal in patients with hematologic malignancies at our center, we found that being divorced, not having defined caregiver support, and not speaking English as the first language made patients more likely to decline a CT. Our sample displayed greater diversity in comparison to the national averages for cancer CT participation despite the predominance of male and non-Hispanic white patients within our sample. This may be representative of the population our center serves. The significance of marital status and caregiver support suggests that support systems are integral in the decision-making process for CTs. Furthermore, the role of divorce in declining trials may be indicative of familial motivation or spousal influence. The significance of English as a first language is notable as our center utilizes an oral translation for informed consent with a short form signature. This suggests that a full translation of CT documents may be beneficial to enrollment. Logistical concerns were frequently cited as a reason for declining, which should be considered by sponsors in the design of CTs as alleviating this burden on patients may help overall recruitment. Limitations of this study include its retrospective nature, manual data extraction, and consistency of research team documentation. The results suggest that introducing support groups and interventions to provide transportation services for trial patients may be beneficial to enrollment and retention. Figure 1 Figure 1. Disclosures Shammo: Abbvie: Current holder of individual stocks in a privately-held company, Research Funding; Astra zeneca: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI pharma: Research Funding; Stemline therapeutics: Research Funding; Kartos Pharma: Research Funding; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; sanofi: Consultancy, Honoraria, Speakers Bureau; Baxter: Current holder of stock options in a privately-held company; Takeda: Consultancy, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Honoraria, Research Funding; NS Pharma: Membership on an entity's Board of Directors or advisory committees. Paner: Adaptive Biotechnologies: Consultancy; Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Oncopeptides: Consultancy; Rush University Medical Center: Consultancy, Current Employment; Sanofi: Consultancy; BMS: Consultancy. Ustun: novartis: Honoraria; Blueprint: Honoraria.

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Quality of Life, Psychological Distress, and Prognostic Awareness in Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2021-146342 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4082-4082

Author(s):

Elizabeth K. O'Donnell ◽

Yael Shapiro ◽

Omar Nadeem ◽

Andrew J. Yee ◽

Jacob P. Laubach ◽

...

Keyword(s):

Psychological Distress ◽

Board Of Directors ◽

Research Funding ◽

Terminal Illness ◽

Symptom Burden ◽

Publicly Traded ◽

Advisory Committees ◽

Line Of Therapy ◽

Patient’S Perception

Abstract Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and prognostic awareness by line of therapy are lacking. Methods: We conducted a cross-sectional, multi-site study of patients undergoing treatment for MM (excluding maintenance therapy) between 6/2020-1/2021. To capture the full spectrum of treatment, we conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2-3 lines; and 3) ≥ 4 lines. Patients completed validated questionnaires to assess their QOL, symptom burden, fatigue, psychological distress, and perceptions of prognosis. We used multivariate linear regression models to examine the association between lines of therapy, QOL, psychological distress, with patient's perception of their prognosis. Results: We enrolled 180 patients with MM (newly diagnosed (n=60), 2-3 lines (n=60), and ≥4 lines of therapy (n=60)). QOL and fatigue scores did not differ by lines of therapy: (QOL: 116.6 (SD=20.6) vs. 112.3 (SD=28.2) vs. 110.6 (SD=29.6); Fatigue: 36.9 (SD=9.9) vs. 35.4 (SD=11.9) vs. 33.7 (SD=12.5). There were also no statistically significant differences in depression, anxiety, or PTSD symptoms by line of therapy. The rate of clinically significant depression, anxiety, and PTSD symptoms were 23.9% (43/180), 23.9% (43/180), and 24.4% (44/180), respectively. Overall, 84% (147/175) of patients reported that it is 'extremely' or 'very' important to know about their prognosis, and the majority (66.1%, 117/177) stated that they had received adequate information regarding their prognosis. Patients reported that prognostic information was 'extremely' or 'very' helpful in making decisions about treatment (93.4%, 155/166), coping with the disease (87.4%, 145/166), and preparing for the future (86.8%, 144/166). Most patients, 84.7% (149/176) reported that their oncologist told them their cancer was incurable but only 30.6% (53/173) acknowledged that they were terminally ill and only 42.0% (73/174) reported that they thought their cancer was incurable . Patients receiving 2-3 lines of therapy were more likely to acknowledge their terminal illness (36.7% vs. 19.6%, p=0.045) and that their MM was incurable (90.0% vs. 75.9%, p=0.047) compared to those receiving 1 st line therapy. QOL and psychological distress were not associated with patient's perception that their MM was incurable. However, patients who acknowledged their terminal illness reported higher depression (B=1.52, P = 0.009), anxiety (B=1.52, P=0.0037), symptom burden (B=7.42, P=0.007), and lower QOL (B=-14.78, p=0.001). Conclusions: MM patients undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, irrespective of their line of therapy. Although the majority reported that their oncologist had told them that their cancer is incurable, a substantial proportion still reported that they believed they were curable. Acknowledgement of terminal illness was associated with higher rates of psychological distress and symptoms burden and lower QOL. Interventions are needed to improve patients' QOL, reduce their psychological distress, and cultivate adaptive coping strategies that may help improve the patient experience over the MM disease course. Disclosures O'Donnell: Adaptive: Consultancy; Oncopeptide: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Karyopharm: Consultancy. Nadeem: Bristol Myer Squibb: Consultancy; GSK: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy. Yee: Adaptive: Consultancy; Bristol Myers Squibb: Consultancy; GSK: Consultancy; Oncopeptides: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Janssen: Consultancy. Branagan: Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy; CSL Behring: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson: Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mo: Epizyme: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Eli Lilly: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Munshi: Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Legend: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Adaptive Biotechnology: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Sperling: Adaptive: Consultancy. Richardson: AbbVie: Consultancy; Takeda: Consultancy, Research Funding; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; AstraZeneca: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; Regeneron: Consultancy; Secura Bio: Consultancy; Celgene/BMS: Consultancy, Research Funding; Sanofi: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other.

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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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Evolving Unmet Need in Patients Refractory to Lenalidomide: Overview of the Clinical Trials in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2020-142642 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Maria-Victoria Mateos ◽

Rohan Medhekar ◽

Istvan Majer ◽

Mehmet Turgut

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Literature Review ◽

Board Of Directors ◽

Unmet Need ◽

Publicly Traded ◽

First Line ◽

Advisory Committees ◽

Line Of Therapy

Introduction: The majority of newly diagnosed multiple myeloma (NDMM) patients are currently treated with lenalidomide-based regimens as their first line of therapy. This trend is likely to continue in the coming years. Typically, lenalidomide is administered until disease progression and has significantly contributed to better outcomes in these patients. However, most patients relapse, and prognosis worsens with each relapse. The choice of optimal treatment for patients who relapse while receiving lenalidomide as first line of therapy is unclear. Moreau et al (Blood Cancer J. 9, 38 [2019]) concluded that there is limited data on approved combinations for treating these patients and are restricted by the low number of lenalidomide-refractory patients enrolled in the pivotal trials. Results from the ongoing clinical trials of the combination of carfilzomib and anti-CD38 antibodies were not available at the time of the Moreau et al publication. The aim of this targeted literature review was to include this new data and to summarize currently available evidence on progression-free survival (PFS) for the treatment of RRMM patients who progressed on lenalidomide-based regimens. Methods: A targeted literature review was conducted to identify registrational clinical trials in patients with RRMM reporting PFS outcomes. PubMed, congress proceedings, and product labels were searched between Jan 2014 to July 2020. In addition to PFS, demographic, disease characteristics and treatment history were extracted for the trial populations to contextualize potential variations in study outcomes. The regimens studied in these trials were classified as lenalidomide-based, proteasome inhibitor (PI)-based and pomalidomide-based. Number of prior lines of therapy, prior exposure and refractoriness to lenalidomide and bortezomib were reported. Results: Twelve registrational trials were identified based on the search criteria (Table 1). Most pivotal trials assessing lenalidomide-based regimens (POLLUX, ELOQUENT-II, TOURMALINE-MM1) except the ASPIRE trial excluded patients who were refractory to lenalidomide. Trials evaluating PI-based regimens (e.g., CANDOR) or pomalidomide-based regimens (e.g., OPTIMISMM) included these patients, with more recent studies enrolling a larger proportion. Percentage of lenalidomide-exposed (and lenalidomide refractory) ranged from 40% (32%) in CANDOR to 98% (90%) in ELOQUENT III. These studies also enrolled a larger proportion of patients who were bortezomib-exposed, although most of these patients were at first relapse, with the exception of ELOQUENT III and ICARIA where most patients were at third relapse. Among lenalidomide-refractory patients, the median-PFS (mPFS) observed for the pomalidomide-based regimens ranged from 9.5 to 10.1 months and that observed for PI-based regimens ranged from 4.9 to 25.7 months. PFS in the lenalidomide-refractory subgroup was considerably shorter than in the ITT population. The mPFS for patients receiving carfilzomib/daratumumab/dexamethasone (KDd; CANDOR) and isatuximab/carfilzomib/dexamethasone (IsaKd; IKEMA) was not reached at median follow-up of 16.9 and 20.7 months respectively. While the mPFS for (KDd) for lenalidomide-refractory patients in CANDOR trial was not yet reached at median follow up of 16.9 months; the mPFS of 25.7 months for KDd in the MMY-1001 trial appears to be the longest among the assessed regimens. Conclusion: Patients refractory to lenalidomide have shorter PFS and represent a population with high unmet need. This targeted literature review suggests that the PI-based KDd regimen provides longer PFS compared to other lenalidomide-sparing regimens in lenalidomide-refractory populations. Heterogeneity across trial populations may limit the comparability of these treatments. Disclosures Mateos: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; GlaxoSmithKline: Consultancy. Medhekar:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Majer:Amgen (Europe) GmbH: Current Employment, Current equity holder in publicly-traded company.

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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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