Outcomes of COVID-19 Infection in Patients with Hematologic Malignancies

The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic on March 11, 2020. This novel virus can cause a rapid progression from cough to acute respiratory distress syndrome and death. Cancer patients infected with COVID-19 were reported to have a 39% incidence of severe events, including admission to intensive care unit (ICU), mechanical ventilation, or death. Patients with hematologic malignancies, especially those undergoing treatment, are a particularly at-risk population due to disease-related impairment of the immune system and chemotherapy-induced neutropenia. The goal of this study is to analyze outcomes of COVID-19 infected patients with hematologic malignancies in order to better understand the impact of SARS-CoV-2 on this vulnerable population. Methods We performed a retrospective analysis on 26 COVID-19 positive patients with hematologic malignancies identified at our center. On July 22, 2020, there were 264 COVID-19 positive patients with hematologic malignancies (including our center's 26 patients) reported to the American Society of Hematology Research Collaborative COVID-19 Registry (ASH RC), a global public reference tool. We extracted our patient's data from each category reported to the ASH RC and compared hospitalization, ICU admissions, and mortality rates between our cohort and the remaining 238 cases. Chi-square test was used for analyses. We also performed a subgroup analysis comparing demographics; type and status of hematologic malignancy, as well as COVID-19 directed treatments between our center's patients and the patients reported to the ASH RC. Results Between March and June 2020, a total of 1265 COVID-19 positive patients were hospitalized at our institution. A significantly higher percentage of COVID-19 patients with hematologic malignancies were hospitalized at our institution compared to the ASH RC (61.5% versus 35.3%, P=. 009). There was no difference in ICU admission rate at our center compared to the ASH RC (23.1% versus 30.2%, P=.45). Significantly less COVID-19 directed therapies were administered at our center compared to the ASH RC (46.2% versus 66.4%, P=.041). Our patients received: 7.7% Remdesivir, 11.5% Tocilizumab, 15.4% hydroxychloroquine, 11.5% azithromycin, 0% convalescent plasma, compared to the ASH RC: 1.7% Remdesivir, 5.5% Tocilizumab, 30.3% hydroxychloroquine, 25.6% azithromycin, 4.6% convalescent plasma. Lastly, our institution had a significantly decreased mortality rate compared to the ASH RC (11.5% versus 29.8%, P=.049). Demographics as well as type and status of hematologic malignancy comparing the two cohorts are shown in Table 1. Conclusions In our comparative analysis, we found that our center's patients were hospitalized significantly more than the ASH RC cohort yet had lower mortality rates. These differences were seen despite similar distribution of malignancy types between the two groups. It should be noted that more patients in our cohort were in remission and none presented at initial cancer diagnosis at the time of infection, which may have contributed to better outcomes. The difference in mortality rates may also be attributed to variance in provider experience, higher percentage of patients >80 years of age reported to the ASH RC, and closer patient monitoring at our center due to a higher hospitalization rate. Differences in ICU admissions were not significant, suggesting a similar rate of severe COVID-19 infection between the two cohorts. Our demographics reflect the urban population we serve with more African Americans and Hispanics compared to the ASH RC. The greater number of COVID-19 directed therapies in the ASH RC cohort compared to ours is likely attributed to the use of convalescent plasma, which was not commonly used as COVID-19 directed treatment at our institution. Limitations of our study include a restricted time frame, small sample size, and the possibility of incomplete datasets within the ASH RC, as stated on the registry's website. In conclusion, we recommend close monitoring and a lower threshold for hospitalizing patients with hematologic malignancies in the setting of COVID-19 infection; however, additional prospective studies are needed to confirm our findings, and further investigate the complications and outcomes of SARS-CoV-2 on this at-risk population. Disclosures Ustun: Kadmon: Honoraria. Shammo:Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Onconova: Research Funding; Incyte: Consultancy, Research Funding, Speakers Bureau; Apellis: Consultancy; Regeneron: Consultancy; Novartis: Consultancy; Agios: Consultancy; Sanofi: Speakers Bureau; Abbive: Current equity holder in publicly-traded company; Baxter: Current equity holder in publicly-traded company; Takeda: Current equity holder in publicly-traded company; Alexion: Consultancy, Research Funding, Speakers Bureau.

Download Full-text

A Comprehensive Clinical Next Generation Sequencing-Based Assay Can Impact Hematopathologic Diagnosis in a Significant Subset of Patients with Hematologic Malignancies

Blood ◽

10.1182/blood.v124.21.2984.2984 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2984-2984

Author(s):

Janine D. Pichardo ◽

Julie T Feldstein ◽

Maria Arcila ◽

Connie Batlevi ◽

Andrew D. Zelenetz ◽

...

Keyword(s):

Next Generation Sequencing ◽

Research Funding ◽

Hematologic Malignancy ◽

Hematologic Malignancies ◽

Genomic Testing ◽

Genomic Profiling ◽

Pathologic Assessment ◽

Somatic Alterations ◽

The Impact ◽

Generation Sequencing

Abstract High throughput genomic studies have identified novel recurrent somatic alterations with prognostic or therapeutic relevance in hematological malignancies. By contrast, few studies have investigated the impact on pathologic assessment, and clinicopathologic diagnosis. We therefore assessed the impact of a CLIA-certified CAP-accredited comprehensive clinical grade next-generation sequencing-based assay, FoundationOne Heme (FOH), on hematopathologic assessment of patients at our institution. The FOH assay targets 405 cancer-related genes and 31 frequently rearranged genes by DNA-capture and sequencing, and 265 frequently-rearranged genes by RNA-capture and sequencing. We prospectively tested 92 cases as part of routine clinical practice, including malignant lymphoid neoplasms (n=51) and suspected myeloid malignancies (n=41). (Table 1) The samples submitted included 30 blood, 38 bone marrow and 24 FFPE specimens. We were able to obtain genomic profiling data in90 of the 92 submitted cases (98%) including all FFPE specimens. A total of 282 genomic abnormalities (range 0-11, average 3.2 abnormalities/case) including substitutions, insertions/deletions and gene fusions were detected. There was excellent concordance between conventional cytogenetic or molecular genetic assays and FOH assay. Only 10 cases lacked any genomic abnormality. Six of these were morphologically normal bone marrows submitted to rule out myeloid neoplasia. Of the 4 remaining cases without recurrent somatic alterations, 2 cases were derived from myeloma patients where the sample analyzed had less than 20% plasma cells and 2 cases were from patients with myelodysplasia with likely low tumor content. In 84 cases with a diagnosis of hematologic malignancy, we identified genomic abnormalities with diagnostic relevance in 42 cases (50%). Most importantly, in 12 cases (14% of cohort), the presence of specific genomic alterations led to a change or refinement of the diagnosis. (Table 2) This included two cases in which a diagnosis of T-LGL was confirmed based on the presence of STAT3 mutations, three cases of lymphoma/myeloma in which a specific diagnosis was reached based on identification of pathogenic fusions/rearrangements, and 4 cases of MPN/MDS which could be confirmed based on the presence of known MPN/MDS disease alleles. In addition, we identified genomic alterations with prognostic relevance in 54 cases (64%), and with potential therapeutic impact in 64 cases (76%). Our data demonstrate that the FOH assay can be performed with a very high success rate (98%) in a routine clinical setting and that comprehensive genomic profiling can substantively impact pathologic assessment and diagnosis of a wide spectrum of hematologic malignancies. Genomic testing provided critical diagnostic information in half of the cases, in some instances refining or changing the conventional pathological diagnosis. These findings suggest that comprehensive targeted genomic testing has an important role to play not only in identifying prognostic and therapeutic targets but also in hematopathology diagnosis, and should be considered as a first line testing platform in hematologic malignancies. Table 1:Clinical characteristicsTotal number of casesN=92 Median age58 (18-82) SexMale58 (63%)Female34 (37%) Myeloid neoplasms33 (36%)AML14MDS11MPN6CMML1CML1 Lymphoid neoplasms51 (55%)DLBCL17B-ALL6TLPD6MCL5Myeloma5CLL3MZL3FL3BCL-NOS2CHL1 Normal marrow6 (7%) Sample failed2 (2%) Genomic abnormalities in hematologic malignancies80/84 (93%)Diagnostic42/84 (50%)Prognostic54/84 (64%)Potential therapeutic64/84 (76%) Table 2: Genomic changes which led to improved diagnosis and classification of the hematologic malignancy Case Diagnosis/Problem Genomic alteration Final/refined diagnosis 1 Neutropenia, T-LGL? STAT3 (N647I) T-LGL 2 Neutropenia, T-LGL? STAT3 (D661Y) T-LGL 3 T-LPD? JAK3 (M511I) T-PLL 4 T-LPD? TET2 (Q1523*), TP53 (R175G) PTCL, NOS 5 Transformed FL CIITA-DSCAML1 (Fusion) PMBL 6 CHL vs ALCL IGH-BCL2 (Rearrang.) DLBCL 7 BCL-NOS IGL-MYC (Rearrang.) BCL between DLBCL/BL 8 Myeloma IGH-MAF8 (Rearrang.) High risk myeloma 9 MDS? STK11 (F354L) RUNX1-MECOM (Fusion) MDS 10 MDS? MLL (ITD) MDS 11 MDS? KDM6A MDS 12 MPN MPL (R514_W515>KK) ET Disclosures Moskowitz: Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech: Research Funding; Merck: Research Funding. Horwitz:Research: Celgene, Millennium, Infinity, Kiowa-Kirin, Seattle Genetics, SpectrumConsulting: Amgen, Bristol-Myers Squibb, Celgene, Jannsen, Millennium, seattle genetics: Consultancy, Honoraria, Research Funding. Stein:Janssen Pharmaceuticals: Consultancy. He:Foundation Medicine: Employment. Stephens:Foundation Medicine, Inc. : Employment, Equity Ownership. Miller:Foundation Medicine: Employment. Younes:Novartis: Research Funding; J & J: Research Funding; Curis: Research Funding; Bayer; Bristol Meyer Squibb; Celgene; Incyte; Janssen R & D; Sanofi; Seattle Genetics; Takeda Millenium: Honoraria. Dogan:Foundation Medicine: Consultancy.

Download Full-text

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.

Download Full-text

Outcomes of Patients with Hematologic Malignancies and COVID-19 Infection: A Report from the ASH Research Collaborative Data Hub

Blood ◽

10.1182/blood-2020-141327 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 7-8

Author(s):

William A. Wood ◽

Donna S. Neuberg ◽

John Colton Thompson ◽

Martin S. Tallman ◽

Mikkael A. Sekeres ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Hematologic Malignancy ◽

Disease Status ◽

Hematologic Malignancies ◽

Morbidity And Mortality ◽

Advisory Committees ◽

Presumptive Diagnosis ◽

Blood Cancer ◽

Hematologic Diseases

Introduction: The coronavirus disease 2019 (COVID-19) is an illness resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019. Many patients with blood cancer have underlying immune dysfunction, and many are treated with chemotherapies and immunotherapies that are themselves profoundly immunosuppressive. Additionally, patients with blood cancer are often older, may have comorbid illness including hypertension and diabetes, and may be especially susceptible to complications of COVID-19 include hypercoagulability and thrombosis. For patients with hematologic malignancies, overall risk of morbidity and mortality from COVID-19 infection, and how this risk varies as a function of age, disease status, type of malignancy, and cancer therapy, has not yet been well defined. Methods: The ASH Research Collaborative COVID-19 Registry for Hematology was developed to study features and outcomes of COVID-19 infection in patients with underlying blood disorders, such as hematologic malignancies. The Registry opened for data collection on April 1, 2020. The Registry is a global effort and is housed on a secure data platform hosted by Prometheus Research, an IQVIA company. The Registry collects data from patients of all ages with a current or history of hematological disease, and either a laboratory-confirmed or presumptive diagnosis of SARS-CoV-2 infection. Data are made available and regularly updated on the ASH Research Collaborative website to guide the provider and patient communities. Data presented here are limited to malignant hematologic diseases only. Contributors are individual providers or designees submitting data on behalf of providers. Results: At the time of this analysis, data from 250 patients with blood cancers from 74 sites around the world had been entered into the Registry. The most commonly represented malignancies were acute leukemia (33%), non-Hodgkin lymphoma (27%), and myeloma or amyloidosis (16%). Patients presented with a myriad of symptoms, most frequently fever (73%), cough (67%), dyspnea (50%), and fatigue (40%). Use of COVID-19-directed therapies such as hydroxychloroquine (N=76) or azithromycin (N=59) was common. Overall mortality was 28%. Patients with a physician-estimated prognosis from the underlying hematologic malignancy of less than 12 months at the time of COVID-19 diagnosis and those with relapsed/refractory disease experienced a higher proportion of moderate/severe COVID-19 disease and death. In some instances, death occurred after a decision was made to forego ICU admission in favor of a palliative approach. Conclusions: Taken together, these data support the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection. However, we see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences. Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The Registry has been expanded to include non-malignant hematologic diseases, and the Registry will continue to accumulate data as a resource for the hematology community. Figure Disclosures Wood: Pfizer: Research Funding; Teladoc/Best Doctors: Consultancy; ASH Research Collaborative: Honoraria. Neuberg:Celgene: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Pharmacyclics: Research Funding. Tallman:Amgen: Research Funding; UpToDate: Patents & Royalties; Bioline rx: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; KAHR: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Delta Fly Pharma: Membership on an entity's Board of Directors or advisory committees; Oncolyze: Membership on an entity's Board of Directors or advisory committees; BioSight: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellerant: Research Funding; Orsenix: Research Funding; ADC Therapeutics: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Rafael: Research Funding; Glycomimetics: Research Funding; Abbvie: Research Funding. Sekeres:BMS: Consultancy; Takeda/Millenium: Consultancy; Pfizer: Consultancy. Sehn:Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Chugai: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria. Anderson:Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees. Goldberg:Dava Oncology: Honoraria; ADC Therapeutics: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Celularity: Research Funding; AROG: Research Funding; Aprea: Research Funding. Pennell:Astrazeneca: Consultancy; BMS: Consultancy; Eli Lilly: Consultancy; Amgen: Consultancy; Genentech: Consultancy; Cota: Consultancy; Merck: Consultancy; Inivata: Consultancy; G1 Therapeutics: Consultancy. Niemeyer:Celgene: Consultancy; Novartis: Consultancy. Hicks:Gilead Sciences: Research Funding.

Download Full-text

Improvement in the Clinical Global Impression of Change with Voxelotor in Patients with Sickle Cell Disease in the Phase 3 HOPE Trial

Blood ◽

10.1182/blood-2020-137121 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 5-6

Author(s):

Wally R Smith ◽

Jane S. Hankins ◽

Miguel R Abboud ◽

Ze Cong ◽

Jonathan Sorof ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Clinical Global Impression ◽

Research Funding ◽

Cell Disease ◽

Publicly Traded ◽

Advisory Committees ◽

Global Impression Of Change ◽

Study Participants ◽

The Impact

Background: Patients with sickle cell disease (SCD) experience varied salient symptoms that impact their health-related quality of life, which incorporates illness severity, their level of distress and other aspects of impairment, and the impact of the illness on functional status. SCD symptoms may begin at an early age, and their severity varies over time and between patients. Although detection of changes in patients' self-assessed symptoms may be obfuscated by their lifelong symptoms, treating physicians with SCD expertise may be able to detect changes in a patient's status given their experience in treating the diverse symptoms across multiple patients. We evaluated the longitudinal impact of voxelotor (Oxbryta®) in the HOPE study using the single-item Clinical Global Impression of Change (CGI-C), a validated clinician-reported outcome analogous to the commonly used Patient Global Impression of Change (PGI-C), which provides expert clinical impressions that transcend symptom checklists. Methods: In the randomized, placebo-controlled, double-blinded HOPE study, participants with SCD aged 12 to 65 years were randomized to receive voxelotor (1500 mg or 900 mg dose administered orally, once daily) or placebo. Study participants had a hemoglobin (Hb) level 5.5 to 10.5 g/dL at enrollment and 1 to 10 vaso-occlusive crises in the past 12 months at screening. Clinicians were blinded to treatment assignment and to all central laboratory measures (eg, hematological parameters) throughout the 72-week study period. Clinicians rated the CGI-C at 24 and 72 weeks from baseline. CGI-C ratings used a 7-point scale ("very much improved," "moderately improved," "minimally improved," "no change," "minimally worse," "moderately worse," and "very much worse"). CGI-C outcomes were stratified by baseline Hb levels and baseline markers of hemolysis to identify measures predictive of assessment outcomes. Results: Trends of improvement from baseline in overall clinical status with voxelotor 1500 mg, as assessed by CGI-C scores, were observed as early as week 24. At week 72, patients receiving voxelotor 1500 mg were more often rated by the clinician as "very much improved" or "moderately improved" (74%; 39 of 53) compared with those who received placebo (47%; 24 of 51) (P<0.01, Figure 1). CGI-C score improvement was consistently greater in participants treated with voxelotor compared with placebo regardless of baseline Hb. Greater proportions of participants were rated "very much improved" or "moderately improved" with voxelotor 1500 mg than placebo regardless of baseline hemolysis markers (indirect bilirubin, percentage reticulocytes, absolute reticulocyte count). Conclusions: Treatment with voxelotor 1500 mg resulted in improved clinician-reported patient outcomes, as assessed using the CGI-C. Greater proportions of participants were rated "very much improved" or "moderately improved" regardless of baseline Hb levels and baseline markers of hemolysis. The CGI provides an overall clinician-determined summary measure that takes all available information into account, including the patient's history, psychosocial circumstances, symptoms, and behavior, as well as the impact of symptoms on the patient's ability to function. Therefore, a tool that provides a holistic assessment of a patient's well-being may be complementary in capturing changes in a patient's status, considering the substantial interpatient and intrapatient variability in SCD symptomatology. CGI-C assessments are being included in ongoing studies of voxelotor. Disclosures Smith: Emmaeus Pharmaceuticals, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Health Resources and Services Administration: Other: Investigator, Research Funding; Incyte: Other: Investigator; Pfizer: Consultancy; Ironwood: Consultancy; Novo Nordisk: Consultancy; Imara: Research Funding; Shire: Research Funding; GlycoMimetics, Inc.: Consultancy. Hankins:American Society of Pediatric Hematology/Oncology: Honoraria; UptoDate: Consultancy; Novartis: Research Funding; MJH Life Sciences: Consultancy, Patents & Royalties; LINKS Incorporate Foundation: Research Funding; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Abboud:Novartis: Consultancy, Honoraria, Research Funding; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Crispr Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Travel support; Eli Lilly: Research Funding; Modus Pharmaceuticals: Research Funding. Cong:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Sorof:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gray:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Hoppe:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Telfer:Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Honoraria, Research Funding; ApoPharma: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

An Insight into the Impact of Hemophilia a on Daily Life According to Disease Severity: A Preliminary Analysis of the CHESS II Study

Blood ◽

10.1182/blood-2020-136952 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 1-3

Author(s):

Declan Noone ◽

Francis Nissen ◽

Tao Xu ◽

Tom Burke ◽

Sohaib Asghar ◽

...

Keyword(s):

Board Of Directors ◽

Disease Severity ◽

Research Funding ◽

Hemophilia A ◽

Daily Life ◽

Social Activity ◽

Publicly Traded ◽

Advisory Committees ◽

On Demand ◽

The Impact

Introduction: Hemophilia A (HA) is a congenital bleeding disorder caused by a deficiency in clotting factor VIII (FVIII). There are currently limited data on the impact of HA on daily life. Here we examine the impact of HA on the daily life of adult persons with HA (PwHA) without current FVIII inhibitors according to disease severity. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey II (CHESS II) is a retrospective, burden-of-illness study in adults with mild, moderate, and severe HA or hemophilia B (defined by endogenous FVIII/IX [IU/dL] relative to normal; mild, 5-<40%; moderate, 1-5%; severe, <1%); this analysis includes only PwHA. Male participants (aged ≥18 years) diagnosed with HA (without FVIII inhibitors) at least 12 months prior to clinical consultation were enrolled from Denmark, France, Germany, Italy, the Netherlands, Romania, Spain, and the UK. Data on clinical outcomes and healthcare resource utilization were captured via electronic case report forms disseminated to hemophilia specialists. PwHA completed a paper-based questionnaire utilizing 5-point Likert scales to assess the disease burden on their daily life. Overall, 12 months' retrospective data were examined. Informed consent was obtained and the study was approved by the University of Chester ethical committee. Results: Of 258 PwHA completing questionnaires, 15.9% (n=41), 27.9% (n=72), and 56.2% (n=145) had mild, moderate, and severe HA, respectively. Of those with severe HA, 60.0% were currently receiving FVIII prophylaxis (standard of care for severe HA); in comparison, 4.9% and 6.9% of those with mild and moderate HA were receiving prophylaxis (Table 1). Treatment adaptation in anticipation of physical or social activity was reported by 19.5%, 23.6%, and 38.6% of those with mild, moderate, and severe HA, respectively. Over a third of participants with mild (36.6%) and moderate (44.4%) HA, and 64.8% of those with severe HA (58.6% with severe HA receiving on-demand treatment and 69.0% receiving prophylaxis) agreed or strongly agreed that HA had reduced their physical activity (Figure 1). Overall, 38.9% of those with moderate HA and 58.6% of those with severe HA (63.8% with severe HA receiving on-demand treatment and 55.2% receiving prophylaxis) agreed or strongly agreed that their HA had reduced their social activity; this was less pronounced in mild HA (9.8%). Additionally, 31.7%, 36.1%, and 64.1% of those with mild, moderate, and severe HA (62.1% with severe HA receiving on-demand treatment and 65.5% receiving prophylaxis) agreed or strongly agreed that their HA had caused them to miss opportunities. Correspondingly, frustration due to HA was felt by 19.5%, 34.7% and 57.9% (56.9% with severe HA receiving on-demand treatment and 58.6% receiving prophylaxis) of people, respectively. When asked whether they believed their daily life was compromised due to their hemophilia, 24.4%, 37.5%, and 63.4% of those with mild, moderate, and severe HA, respectively, agreed. Pain, as reported by the physician, was noted in 36.6% of people with mild HA (100% was reported as 'mild'); in people with moderate HA, pain was reported as 'mild', 'moderate', and 'severe' in 44.4%, 20.8%, and 1.4% of PwHA, respectively. In people with severe HA, pain was reported as 'mild', 'moderate', and 'severe' in 39.7%, 27.6%, and 8.6% for those receiving on-demand treatment, and 37.9%, 32.2%, and 8.0% for those receiving prophylaxis, respectively. Conclusions: In all disease severity groups, there was a notable group of PwHA that felt that they have had to reduce their physical and social activity, have had fewer opportunities and are frustrated due to their disease. While the impact on daily life is most pronounced in people with severe HA (including those receiving on-demand treatment and those receiving prophylaxis), it is also apparent in mild and moderate HA, indicating that there may be an unmet medical need in these groups. Disclosures Noone: Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees. Nissen:F. Hoffmann-La Roche Ltd: Current Employment; Actelion: Consultancy; Novartis: Research Funding; GSK: Research Funding. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Burke:University of Chester: Current Employment; HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar:HCD Economics: Current Employment. Dhillon:F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; HCD Economics: Current Employment. 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. Khair: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; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Haemnet: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Platform Incorporating Patient Navigation, Preparative Guidelines, and Hospital at Home May Improve COVID-19 Outcomes for Patients with Myeloid Malignancies

Blood ◽

10.1182/blood-2021-150610 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3019-3019

Author(s):

Brittany Knick Ragon ◽

Tamara K. Moyo ◽

Ashley Sumrall ◽

Ifeyinwa (IFY) Osunkwo ◽

Kris Blackley ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Active Treatment ◽

Research Funding ◽

Hematologic Malignancy ◽

High Risk Population ◽

Advisory Committees ◽

Risk Population ◽

Myeloid Malignancies ◽

Hospital At Home

Abstract Background: Patients (pts) with malignancies are at increased risk of morbidity and mortality from COVID-19. Among these pts, some of the higher case fatality ratios (CFR) reported are among pts with myeloid malignancies, ranging from 37 to 50% (Mehta V, Cancer Discov 2020; Ferrara F, Leukemia 2020). Levine Cancer Institute (LCI) has a robust hematologic malignancy and cellular therapy program that serves many pts with myeloid malignancies, seeing nearly 100 new diagnoses of acute myeloid leukemia per year. A strategy to mitigate risks associated with COVID-19 was established at LCI in partnership with Atrium Health's (AH) Hospital at Home (HAH). HAH was a system wide platform using telemedicine and home health services to assess and monitor COVID-19 + pts at high risk of complications. To augment HAH for our medically complex cancer pts, a virtual health navigation process involving expertise from across LCI, including a specialized nurse navigation team, was developed to rapidly identify LCI pts + for SARS-CoV-2, monitor them under physician supervision, and escalate care as needed with AH HAH. Along with the navigation platform, data-driven guidelines for detecting, monitoring, and managing LCI pts + for SARS-CoV-2 were swiftly employed across the extensive LCI network. Herein we report on the outcomes for LCI pts with myeloid malignancies + for SARS-CoV-2 and outline the employed risk mitigation strategies and their potential impact on these outcomes. Methods: An automated daily list of LCI pts + for SARS-CoV-2 was provided by AH Information Services. Each pt's chart was reviewed by a nurse navigator for hematologic or oncologic diagnosis, outpatient or inpatient status, and COVID-19 symptoms. Pts without a cancer diagnosis were not assigned a navigator. If hospitalized, a pt was not assigned a navigator; following discharge, if enrolled in HAH, a navigator was assigned. In collaboration with HAH, an algorithm for directing care was utilized (Figure 1). A diagnosis-specific navigator contacted and screened the pt with an assessment tool, which scored pts for surveillance and treatment needs (Table 1). Documentation was forwarded to the primary hematologist/oncologist. Comprehensive guidelines for testing, scheduling, management of + pts, research, and process changes were created, disseminated, and actively updated through LCI's EAPathways. For outcome analysis for pts with myeloid malignancies, pt vital status was updated through data cutoff (7/3/21). Results: From inception on 3/20/20 to 12/2/20, 974 LCI patients were identified as SARS-CoV-2 + and reviewed for nurse navigation. Of the 974 pts, including pts with benign and malignant diagnoses, 488 were navigated. Among all SARS-CoV-2 + LCI pts, 145 (15%) had a hematologic malignancy, including 37 (4%) pts with myeloid malignancies. Characteristics are shown in Table 2. Of the 37 pts, 18 (49%) were navigated. 70% with myeloid malignancies were on active treatment at the time of + test. Nearly 50% of those on active treatment were navigated. 46% were hospitalized with COVID-19, with this being the main reason for no assigned navigator. 24% of hospitalized pts were eventually assigned a navigator. Only 3 pts had undergone allogeneic stem cell transplantation (allo-SCT) with a median time from transplant to detection of SARS-CoV-2 of 9 months (range, 7-23). 2 out of 3 cases post allo-SCT were asymptomatic. No pt died from COVID-19 following allo-SCT. Among the navigated pts with myeloid malignancies, there was no death related to COVID-19. 4 pts, all of whom were hospitalized, died from COVID-19 (N=2, myelodysplastic syndrome with 1 on azacitidine; N=2, myeloproliferative neoplasm, both on hydrea). A CFR of 11% was demonstrated for LCI pts with myeloid malignancies. Conclusions: A multidisciplinary response strategy liaising between AH HAH and LCI followed, assessed, and assisted cancer pts + for SARS-CoV-2. With our embedded nurse navigation team's specialized attention along with enhanced physician oversight and close collaboration with AH HAH, opportunities for care escalation or adjustments in cancer-focused care were promptly identified. In this setting, among the high-risk population of pts with myeloid malignancies, a lower CFR than has been reported was observed. A virtual navigation platform with HAH capabilities is a feasible, safe, and effective way to monitor and care for this high-risk population. Figure 1 Figure 1. Disclosures Moyo: Seattle Genetics: Consultancy. Chai: Cardinal Health: Membership on an entity's Board of Directors or advisory committees. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Grunwald: Amgen: Consultancy; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Stemline: Consultancy; Bristol Myers Squibb: Consultancy; PRIME: Other; Trovagene: Consultancy; Blueprint Medicines: Consultancy; AbbVie: Consultancy; Med Learning Group: Other; Pfizer: Consultancy; Sierra Oncology: Consultancy; Janssen: Research Funding; Incyte: Consultancy, Research Funding; Gilead: Consultancy; MDEdge: Other; PER: Other; Cardinal Health: Consultancy; Karius: Consultancy. Copelan: Amgen: Consultancy.

Download Full-text

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.

Download Full-text

Addition of Cyclophosphamide, on Demand, to Lenalidomide and Corticosteroids in Patients with Relapsed/Refractory Multiple Myeloma, a Retrospective Review of a Single Centre Experience

Blood ◽

10.1182/blood.v126.23.1842.1842 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1842-1842

Author(s):

Majed Alahmadi ◽

Esther Masih-Khan ◽

Eshetu G Atenafu ◽

Limore Arones ◽

Christine Chen ◽

...

Keyword(s):

At Risk ◽

Confidence Interval ◽

Research Funding ◽

Progression Free Survival ◽

Free Survival ◽

Lower Upper ◽

Start Date ◽

On Demand ◽

Grade 3 ◽

The Impact

Abstract Introduction The lenalidomide + dexamethasone combination (Len-dex) is an established regimen for myeloma patients (pts) with relapsed or refractory disease. In order to prolong the benefit of this effective regimen, the Myeloma Program at Princess Margaret Cancer Centre has routinely added a third agent, oral weekly cyclophosphamide (Cy), to Len-dex at the time of progression. We have now retrospectively analyzed the results of this pt cohort to assess the response rate (RR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and toxicity of the Len-dex-Cy regimen subsequent to progression on Len-dex. Methods The Princess Margaret Myeloma Database identified 54 patients that received Len-dex-Cy for a minimum of 4 weeks following Len-dex as a doublet between 12/2007-12/2014. Hematologic responses were assessed using modified IMWG consensus criteria. Survival times were measured in months both from the start of Len-dex and the time of addition of Cy up to date of event of interest or end of follow-up. The impact of diagnostic and clinical variables on PFS and OS were also assessed in both cases using the log rank test. Results Baseline pt characteristics at addition of Cy included: median age 66 yrs; Hgb 107 g/L; creatinine 76 umol/L; albumin 36g/L; ANC 2.5 109/L; and median platelet count 158 109/L . Myeloma isotypes were IgG (61%), IgA (19%), and FLC (20%). The median number of prior regimens including Len-dex was 2; 80% pts had undergone prior ASCT. The dose of added Cy ranged between 250-500mg once weekly. Twenty-six percent patients experienced dose reductions primarily due to cytopenias. Overall, Len-dex-Cy was well tolerated with grade 3-4 toxicities in < 20% (Table 1). The mean duration of Len-Dex-Cy therapy was 8.9 months (range 0.9 - 37.7). The overall RR (≥ PR) was 41%; however clinical benefit was seen in 85% (≥ SD) pts. The median PFS was 8 months (95 % CI 5.8- 10.3 months) from addition of Cy and 25 months (95 % CI 17.3- 32.5 months) from start of Len-dex. The median OS was 24.5 months (95 % CI 15.2-41.8 months) from addition of Cy and 50.1 months (95 % CI 40.6-70.4 months) from start of Len-dex (Figure 1). Significant adverse factors for PFS were del(13q) from start of Len-dex and presence of anemia at the time of addition of Cy (p=0.027) and (p=0. 031) respectively. Decreased baseline serum albumin at the time of addition of Cy was identified as a significant factor for shorter OS (p=0.004). Conclusions 1) The addition of Cy in pts with myeloma progressing on Len-dex resulted in a clinically meaningful extension of disease control with an acceptable safety profile; 2) The effectiveness of adding a third agent to pts with progression on a doublet regimen raises the possibility that only a limited number of resistant myeloma clone(s) is/are responsible for the progression; 3) Although subject to many limitations, the results of this sequential "on demand" approach compare favorably with our previously reported phase 2 study of the Len+ prednisone+ Cy ("CPR") regimen in which triple-drug therapy was given throughout (PFS: 25 vs 16.1 months; OS: 50.1 vs 27.6 months) (Reece et al, Br J Haematol 2015; 168: 46-54); 4) future prospective studies evaluating a strategy of adding a third agent to a doublet ( such as Len-dex) "on demand" versus using triple therapy throughout the relapse would be worthwhile; a number of potential agents, including Cy as well as other newer anti-myeloma drugs, might be candidates for such studies. Table 1. Grade 3-4 toxicities associated with Len-Dex-Cy therapy in Len-dex relapsed patients Toxicity No. of patients (%) Grade 3-4 Thrombocytopenia 4 (7.7) Grade 3-4 Anemia 10 (18.8) Grade 3-4 Hematuria 1 (1.9) Febrile Neutropenia 2 (3.9) Infections 7 (12.9) Secondary Malignancy 2 (3.7) Table 2. Years PFS Rate 95% Confidence Interval Status Lower Upper Events so far Number at risk 1 0.8675 0.74204 0.93454 7 45 2 0.5591 0.41457 0.68112 23 29 3 0.3433 0.21795 0.47228 34 15 Table 3. Years OS Rate 95% Confidence Interval Status Lower Upper Events so far Number at risk 1 0.9426 0.83250 0.98114 3 48 2 0.7428 0.59831 0.84183 13 37 5 0.4136 0.25436 0.56596 25 11 Figure 1. Progression Free Survival (PFS) from the start date of Len-Dex Figure 1. Progression Free Survival (PFS) from the start date of Len-Dex Figure 2. OS of patients from start date of Len-Dex with 95% CI Figure 2. OS of patients from start date of Len-Dex with 95% CI Disclosures Chen: Celgene: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria; Roche: Honoraria; Janssen Ortho: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria. Tiedemann:Amgen: Honoraria; Janssen Ortho: Honoraria; Celgene: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Reece:Amgen: Honoraria; Bristol-Myers Squibb: Research Funding; Lundbeck: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Onyx: Consultancy; Otsuka: Research Funding; Millennium Takeda: Research Funding; Otsuka: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria; Lundbeck: Honoraria; Novartis: Honoraria, Research Funding; Millennium Takeda: Research Funding.

Download Full-text

Infection at the Time of Initial Therapy for Hairy Cell Leukemia Is Associated with Inferior Time to Next Treatment

Blood ◽

10.1182/blood-2018-99-119951 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2305-2305 ◽

Cited By ~ 1

Author(s):

Narendranath Epperla ◽

Mirela Anghelina ◽

Qiuhong Zhao ◽

Akwasi Agyeman ◽

James S. Blachly ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Research Funding ◽

Nucleoside Analogs ◽

Small Sample ◽

Hairy Cell ◽

Cell Leukemia ◽

Infection Group ◽

Increased Risk ◽

Significant Difference ◽

The Impact

Abstract Introduction: Hairy Cell Leukemia (HCL) is a rare, chronic hematological malignancy that makes up approximately 2% of all leukemias. HCL patients are at a markedly increased risk for infection related to a combination of disease-related and treatment-related immunosuppression which has been well described in the literature. However, the significance of infection prior to initiation of HCL therapy and its impact on the subsequent selection of HCL treatment, or outcomes, is not well described. Using the HCL patient data registry, we report here the impact of antecedent infection on the treatment patterns and outcomes of HCL patients. Methods: We evaluated adult (≥18 years) patients with HCL who had information regarding antecedent infections and subsequent HCL treatment during 1984-2018. The primary endpoint was progression-free survival (PFS-1). Secondary endpoint included time to next treatment (TTNT). PFS-1 was measured from the date of first HCL treatment to date of progression/death or last follow-up. TTNT was defined as the time from first HCL treatment to initiation of second HCL treatment. The study population was stratified into 3 groups based on the presence or absence of antecedent infections: no infection prior to first HCL treatment (no infection group), infection within 30 days prior to first HCL treatment (infection1 group) and infection >30 days prior to first HCL treatment (infection2 group). Fisher's exact test or Kruskal-Wallis test was used to compare the characteristics among the no infection and infection groups and the Cox proportional hazard model was used to evaluate the association with PFS-1 and TTNT. Results: A total of 205 HCL patients who had information regarding antecedent infections and subsequent HCL treatment were eligible for the study. Among these, 144 (70%) belonged to the no infection group, while 26 patients (13%) belonged to infection1 group and 35 (17%) to infection2 group. Patient characteristics are shown in Table 1 with a breakdown between the three groups. The majority of the patients were Caucasian with a male preponderance and had classic HCL. The patients in the infection1 group had a lower median WBC (K/uL) (1.9 vs 3.1 vs 2.9), particularly the absolute neutrophil count (K/uL) (0.4 vs 0.7 vs 0.8) and significantly lower median hemoglobin (gm%) (10.1 vs 12.2 vs 12.4) relative to the no infection and infection2 groups, respectively (p=0.01). Similarly, a greater proportion of patients in the infection1 group had significant comorbidities (including pulmonary, gastrointestinal and hepatic disease) relative to no infection and infection2 groups as shown in Table 1. The majority of patients received purine nucleoside analogs as their first HCL treatment (no infection group=92%, infection1 group=85%, infection2 group=94%). The median PFS-1 (in years) was better in the no infection group compared to the infection1 group but was not statistically significant (17.0 [95% CI=7.9-not reached (NR)] vs 8.8 [95% CI=4.2-NR], respectively, p=0.98, Figure 1). However, the median TTNT (in years) was significantly longer for HCL patients with no infection versus the infection1 group (6.3 [95% CI=5.4-7.8] vs 3.6 [95% CI=0.7-NR], respectively, p=0.001, Figure 1). On subgroup analysis, relative to the no infection group, median PFS-1 (in years) was not significantly different in infection1 group treated with Pentostatin (10.7 [95% CI=3.53-NR] vs NR [95% CI=1.38-NR], respectively, p=0.43), however, the median PFS-1 (in years) was shorter in the infection1 group treated with Cladribine (17.0 [95% CI=7.67-NR] vs 4.0 [95% CI=2.00-NR], respectively), although not reaching statistical significance (p=0.09) probably due to small sample size. Conclusion: In this large series of HCL patients who received treatment, we show that the patients who had infections at the time of HCL treatment have a significantly shorter TTNT. The reasons for this are unclear but may indicate that patients were unable to receive treatment in a timely manner because of the infection, or were unable to complete treatment because of complications. The significant difference in hemoglobin between the infection1 and other groups indicates the possibility that these patients had more advanced HCL at the time of diagnosis. These findings indicate the potential long term negative impact of infections in patients who need treatment for HCL and reinforce the need for careful management in this setting. Disclosures Lozanski: Beckman: Research Funding; Coulter: Research Funding; Stem Line: Research Funding; Genentech: Research Funding; Novartis: Research Funding; BI: Research Funding. Andritsos:HCLF: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy.

Download Full-text

Financial Hardship Amongst Patients with Hematologic Malignancies: Using the EMR to Streamline and Prioritize Patient-Centered Care

Blood ◽

10.1182/blood-2021-150546 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 661-661

Author(s):

Sandeep S Voleti ◽

Nandita Khera ◽

Carolyn Mead-Harvey ◽

Sikander Ailawadhi ◽

Rafael Fonseca ◽

...

Keyword(s):

Board Of Directors ◽

Cancer Patients ◽

Mayo Clinic ◽

Research Funding ◽

Hematologic Malignancy ◽

Hematologic Malignancies ◽

Cancer Center ◽

Patient Centered ◽

Advisory Committees ◽

Alaskan Native

Abstract Background: Self-reported financial hardship (FH) amongst cancer patients is increasingly becoming a challenge for patients, caregivers, and healthcare providers. FH not only leads to financial struggles, significant lifestyle changes, and emotional distress, but also contributes to treatment noncompliance, affecting clinical outcomes. As treatment costs rise, it is crucial to develop efficient methods to proactively identify and alleviate FH in hematology practice. One potential approach is utilizing automated processes to identify those at highest risk of FH. At Mayo Clinic, screening for FH involves using a single financial strain question 'How hard is it for you to pay for the very basics like food, housing, medical care, and heating?' which all cancer patients answer annually as part of the institution's Social Determinants of Health (SDOH) assessment. Answers are on a five-point scale including not hard at all, not very hard, somewhat hard, hard, and very hard. In this study, we assess the prevalence and predictors for FH (denoted by a response of "Very hard" "Hard" or "Somewhat hard") amongst the Mayo Clinic hematologic malignancy patient population. Our study objective was to determine if this automated process could identify those at risk for FH. Methods: Patients who received care for hematologic malignancies (lymphoma, leukemia, plasma disorders, myelodysplastic/myeloproliferative disorders, and other heme malignancies) at any of the Mayo Clinic cancer centers (Minnesota, Arizona, and Florida) and who had completed the SDOH screen at least once were included in this study. The electronic medical record (EMR) and Mayo Clinic Cancer Registry were utilized to extract demographic and disease variables. Patient's home zip code was used to determine rural/urban residence, distance from cancer center, and the Area Deprivation Index (ADI), a measure of socioeconomic disadvantage based on home zip code (ranging from 1-100, with 100 representing the most disadvantaged). Multivariable logistic regression modeling was used to examine predictor variables for FH in this patient population. Results: The final cohort included 10,024 patients from 2018 to 2020. Median age was 64.6 years (IQR 58.1,73.7), 58% were male, and 79% married. Race/ethnicity composition was 94% White (n=9,268), 2.5% Black (n=246), 0.4% American Indian/Alaskan Native (44), and 4% Hispanic (n=360). Fifty-six percent of patients had Medicare and 41% had commercial insurance. Fifty percent were retired, 40% were working/students, and 72% were urban residents. Mean ADI was 41.2. Fifty-six percent of patients had lymphomas, 23.5% had plasma cell disorders, 8.5% had leukemias, 6.8% had other hematological malignancies, and 5.5% had myelodysplastic/myeloproliferative neoplasms. FH was reported by 12.8% (n=1286) of the patients. Table 1 shows the results of the multivariable model. A significantly higher likelihood of endorsing FH was noted in Hispanic vs non-Hispanics, Black and American Indian/Alaskan Native groups vs whites, Disabled/Unemployed vs working, Medicaid, Medicare, and Self-Pay groups vs commercial insurance, higher ADI (5 th quintile vs 1 st), and myelodysplastic/myeloproliferative disorder and other hematologic malignancy vs lymphoma patients. Older age, being retired, and living farther from the cancer center were associated with significantly less likelihood of endorsing FH. Conclusion: Our study used automated data extraction from the EMR to efficiently identify predictors of FH in hematologic cancer patients. Employing a dichotomized and automated "flag" for FH, particularly if incorporated in the EMR, could ease the identification of SDOH issues, facilitate timely connection to appropriate resources, and help provide better patient-centered care. Figure 1 Figure 1. Disclosures Ailawadhi: Sanofi: Consultancy; Cellectar: Research Funding; Karyopharm: Consultancy; Ascentage: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Beigene: Consultancy; GSK: Consultancy, Research Funding; AbbVie: Consultancy; Medimmune: Research Funding; Pharmacyclics: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Xencor: Research Funding. Fonseca: OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; BMS: Consultancy; Mayo Clinic in Arizona: Current Employment; Aduro: Consultancy; AbbVie: Consultancy; GSK: Consultancy; Merck: Consultancy; Juno: Consultancy; Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; Novartis: Consultancy; Bayer: Consultancy; Celgene: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy. Griffin: Exact Sciences: Research Funding.

Download Full-text