Impact of Race/Ethnicity on Cancer Associated Thrombosis Among Underserved Patients with Cancer

Abstract Introduction: Cancer-associated thrombosis (CAT) is common among patients with cancer. Risk factors for CAT include type of malignancy, advanced stage, and chemotherapy treatment, but the association of CAT with race and ethnicity remains controversial. Identifying the incidence of CAT among populations susceptible to inequalities in healthcare delivery may help delineate preventive strategies. Methods: We performed a retrospective cohort study at Harris Health System (HHS), a safety-net healthcare system that provides care for underserved minorities and uninsured patients in Houston, TX. We created an integrated database that linked consecutive patients with newly diagnosed invasive cancer with structured electronic health record (EHR) data from 2011-2020 (Figure 1). We followed patients from time of cancer diagnosis to time of first VTE, death, or loss of follow-up. VTE was defined as radiologically confirmed pulmonary embolism (PE), lower extremity deep vein thrombosis (LE-DVT), catheter-related DVT (CR-DVT), or splanchnic vein thrombosis in either inpatient or outpatient setting. We used VTE ICD9/ICD10 billing codes to assess for potential events and confirmed incident, recurrent, and historical events through medical record review. VTE occurring within 30 days prior to cancer diagnosis were considered as CAT at diagnosis. Incidence rates were assessed per 100 person-year (py) within 1 year of diagnosis and stratified by race/ethnicity, cancer type, and cancer stage. Cumulative incidence of VTE was assessed through competing risk method with death as the competing cause. Multivariable Fine-Gray competing risk models were performed to determine the effect of race/ethnicity on the risk of CAT, adjusted for age, sex, body mass index, insurance, cancer site, stage, systemic therapy, recent hospitalization, and prior history of VTE. Results: A total of 9,353 cancer patients were included in the study, where 49.3% were Hispanics, 27.6% were Non-Hispanic Blacks (NHB), 15.5% were Non-Hispanic Whites (NHW), and 7.6% were Asian/Pacific Islander (PI). Most patients (74.7%) were uninsured, 35.8% were obese, 19% had recent hospitalization, and 31.9% had stage IV disease. Overall, 832 developed CAT within 1 year, including 49.4% PE, 28.1% LE-DVT, and 17.1% CR-DVT. The median onset was 69 days (IQR 20-154), but a significant proportion (n=92) was diagnosed in the month before diagnosis. The incidence of CAT was 7.3% at 6 months and 9.6% at 1 year. The overall incidence rate was 11/100 py with a similar trend from 2011 to 2020. Figure 2 shows the variation in incidence rates for different cancer types across stages. The rate increased 2- to 10-fold from stage I to IV, reaching >40/100 py among patients with pancreatic and upper gastrointestinal cancers. Figure 3 shows the impact of race/ethnicity on the incidence of CAT, with 9.3% and 8.4% for NHW and NHB at 6 months, compared to 6.5% and 3.8% for Hispanics and Asian/PI, respectively. In the adjusted multivariable analysis, the risk of CAT remained lower in Hispanics vs. NHW (SHR 0.80 [0.65-0.97]) and Asian/PI vs. NHW (SHR 0.48 [0.32-0.73]). There was no difference in NHB vs. NHW (SHR 1.04 [0.84-1.27]). Other important covariates included history of VTE (SHR 2.29 [1.32-3.97]) and prolonged hospitalization (SHR 1.53 [CI 1.31-1.80]) in addition to staging and cancer types. Compared to no systemic therapy or adjuvant endocrine only, there was a higher incidence of VTE in patients receiving chemotherapy (SHR 1.72 [1.39-2.15]), targeted therapy (SHR 1.58 [1.12-2.23]), immunotherapy (SHR 2.13 [1.30-3.48], but not non-adjuvant endocrine therapy (SHR 0.91 [0.40-2.08]). Conclusion: In the current cancer registry-linked EHR cohort with a high proportion of Hispanics and Blacks from a large safety-net healthcare system in the US, we have observed a high incidence rate of CAT at 11/100 py. This rate is much higher than 3.9-5.8/100 py reported in contemporary cancer registries in Europe (PMID 27709226, 33171494), and likely reflects advanced disease and comorbidity at the time of diagnosis due to delayed care from the lack of health insurance. Despite adjusting for patient-, cancer-, and treatment-specific confounders, we found that Hispanics and Asian/PI had ~20% and ~50% lower rate of VTE, respectively, compared to NHW or NHB. This racial/ethnicity difference should be considered in future risk assessment models for CAT. Figure 1 Figure 1. Disclosures Carrier: Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Honoraria; Servier: Honoraria.

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Real-World Use of Therapeutic Anticoagulation in Patients with Paroxysmal Nocturnal Hemoglobinuria. Results of a Survey of Physicians in Australia

Blood ◽

10.1182/blood.v126.23.4537.4537 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4537-4537

Author(s):

Jeffrey Szer ◽

Cecily J Forsyth ◽

Anja Giese

Keyword(s):

Board Of Directors ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Primary Prophylaxis ◽

Secondary Prophylaxis ◽

Prior History ◽

Advisory Committees ◽

Vein Thrombosis ◽

Therapeutic Anticoagulation ◽

Increased Risk ◽

History Of

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematopoietic stem cell disorder characterized by uncontrolled complement-mediated hemolysis. Patients with PNH are at increased risk of thromboembolism and premature death. This risk is predominantly due to the effects of chronic hemolysis and platelet activation. Eculizumab, a monoclonal antibody that inhibits terminal complement activation, has been shown to reduce hemolysis and dramatically reduce the rate of thromboembolism. A previous publication (Kelly et al, 2011) suggested that cessation of therapeutic anticoagulation (TAC) in PNH patients on eculizumab with no prior history of thrombosis is safe. There are very few reports on the outcomes of cessation of TAC in PNH patients on eculizumab who have a prior history of thrombosis or on the use of non-vitamin K antagonist oral anticoagulant (NOAC) agents in PNH patients with a history of thrombosis. In Australia, patients with PNH are predominantly managed by individual hematologists rather than at a single centre and hence anticoagulation practices following the introduction of eculizumab therapy are variable. We surveyed Australian hematologists managing eculizumab-treated patients with PNH to obtain the details of anticoagulation management and incidence of thrombotic events in their patients. We received responses from 30 hematologists caring for a total of 58 patients with PNH on eculizumab (1-17 patients per hematologist) and the table summarises the results. TAC as primary prophylaxis had been ceased in 10 patients with no recurrent thrombotic events. One (1) patient remains on primary prophylaxis due to persistently high D-dimer and factor VIII levels. TAC for secondary prophylaxis had been ceased in 2 patients due to bleeding (1 patient with subdural hematoma, 1 patient with gastrointestinal bleeding) and neither of these patients had a further thrombotic event. One patient, with a prior history of thrombosis, requested cessation of TAC and subsequently developed a provoked thrombosis. Three patients not receiving TAC when eculizumab was commenced developed thrombosis; two (2) patients had provoked deep venous thromboses and one patient developed a splanchnic vein thrombosis following a cholecystectomy in association with severe sepsis. One patient had a portal vein thrombosis immediately prior to commencing eculizumab therapy but has never received TAC due to severe coexistent thrombocytopenia from myelodysplasia. This patient has not had a recurrent thrombosis. Three (3) patients with thrombotic events prior to eculizumab therapy (1 patient with pulmonary emboli, 1 patient with cerebral venous sinus thrombosis and 1 patient with inferior vena cava thrombosis) had anticoagulant therapy changed from warfarin to rivaroxaban. At a follow-up of at least twelve months for all 3 patients there have been no recurrent thrombotic events and no bleeding complications. In conclusion, these Australian data are consistent with those reported by Kelly suggesting that cessation of primary prophylaxis in PNH patients on eculizumab is safe. Cessation of TAC in PNH patients on eculizumab with a prior thrombosis can be considered if there are clear contraindications to anticoagulation. Thromboprophylaxis in situations of increased risk of venous thromboembolism remains essential for all PNH patients not on TAC, even when they are on eculizumab therapy. The three patients on rivaroxaban as secondary prophylaxis are, to our knowledge, the first reported patients with PNH treated on a NOAC. Table. Number of patients New thrombotic events Eculizumab treated 58 Ceased TAC: Total1. As 1o prophylaxis2. As 2o prophylaxis(i) Due to bleeding(ii) At patient request 1410431 -None-None1 (provoked) TE in patients not on TAC at commencement of eculizumab 3 3 (provoked) NOAC as 2o prophylaxis 3 None Disclosures Szer: Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Australia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Forsyth:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giese:Alexion: Employment.

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Frequency, demographics and risk (according to tumour type or site) of cancer-associated thrombosis among patients seen at outpatient DVT clinics

Thrombosis and Haemostasis ◽

10.1160/th09-06-0397 ◽

2010 ◽

Vol 103 (02) ◽

pp. 338-343 ◽

Cited By ~ 42

Author(s):

Shankaranarayana Paneesha ◽

Aidan McManus ◽

Roopen Arya ◽

Nicholas Scriven ◽

Timothy Farren ◽

...

Keyword(s):

Cancer Patients ◽

Similar Rate ◽

Cancer Type ◽

Tumour Site ◽

Vein Thrombosis ◽

Patients With Cancer ◽

Skin Cancers ◽

Cancer Types ◽

Cancer Associated Thrombosis ◽

Deep Vein

SummaryVenous thromboembolism (VTE) is a clinically important complication for both hospitalised and ambulatory cancer patients. In the current study, the frequency, demographics and risk (according to tumour site) of VTE were examined among patients seen at outpatient DVT (deep-vein thrombosis) clinics. Of 10,015 VTE cases, 1,361 were diagnosed with cancer, for an overall rate of cancer-associated VTE of 13.6% in this outpatient population. Patients with cancer-associated VTE were significantly older than cancer-free VTE cases (66.4 ± 12.7 vs. 58.8 ± 18.5 years; p<0.0001). The frequency of cancer-associated VTE peaked earlier among females than males, occurring in the sixth (137/639, 21.4% vs. 98/851, 11.3%; p<0.001) and seventh decades (213/980, 21.7% vs. 197/1096, 18%; p=0.036). VTE was described most frequently in common cancers – breast, prostate, colorectal and lung (56.1% of cases). The risk of VTE varied widely across 17 cancer types. Calculating odds ratios (OR) to assess the effect size of cancer type on VTE risk, the highest odds were observed for patients with pancreatic cancer (OR 9.65, 95% confidence interval [CI] (5.51–16.91). Tumours of the head and neck had higher odds than previously reported (OR 8.24, 95% CI 5.06–13.42). Reduced risk estimates were observed for skin cancers (melanoma and non-melanoma: OR 0.89, 95% CI 0.42–1.87; OR 0.74, 95% CI, 0.32–1.69, respectively). We conclude that outpatients have a similar rate of cancer-associated VTE as VTE patient populations previously reported, that cancer-associated VTE occurs in an older age group and earlier in females and that outpatients exhibit distinct tumour site-specific risk from that described among hospitalised cancer patients.

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Current Practice Patterns and Patient Persistence on Anticoagulant Treatments for Cancer-Associated Thrombosis

Blood ◽

10.1182/blood.v126.23.626.626 ◽

2015 ◽

Vol 126 (23) ◽

pp. 626-626 ◽

Cited By ~ 6

Author(s):

Alok A. Khorana ◽

Keith McCrae ◽

Dejan Milentijevic ◽

Jonathan Fortier ◽

Winnie Nelson ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Initial Therapy ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Patients With Cancer ◽

Kaplan Meier ◽

Equity Ownership ◽

Cancer Associated Thrombosis

Abstract Introduction: Therapeutic options for the management of venous thromboembolism (VTE) in patients with cancer remain limited. Guidelines recommend anticoagulation with low molecular weight heparin (LMWH) monotherapy for ≥3-6 months, and possibly indefinitely, for patients with active cancer. However, drug cost and patient preference issues may lead to non-compliance with these recommendations. The objective of this study is to describe current treatment patterns and to evaluate patient persistence on various anticoagulants. Methods: Medical and pharmacy claims from the Humana Database were analyzed. To reflect recent treatment patterns, the study population was restricted to patients who had their first VTE between 1/1/2013 and 12/31/2014. Newly diagnosed cancer patients with a first VTE diagnosis (deep vein thrombosis [DVT] or pulmonary embolism [PE]) occurring after their first cancer diagnosis (a 30-day window before the cancer diagnosis was allowed), and with ≥1 dispensing of an anticoagulant agent within 30 days after their VTE diagnosis, were selected. Based on the first anticoagulant agent received, patients were classified into one of the following cohorts: LMWH, LMWH/warfarin, warfarin and rivaroxaban. Use of other anticoagulants including fondaparinux, heparin, apixaban, or dabigatran was low and could not be analyzed due to small sample size. The observation period spanned from the date of the first anticoagulant dispensing to the end of insurance eligibility or the end of data availability, whichever occurred earlier. Discontinuation of the index therapy was defined by a time gap without refill of the index anticoagulant for more than 60 days after the presumed exhaustion of the last known dispensing. For patients in the LMWH/warfarin group, the 2 medications were filled simultaneously as an index therapy, with the expectation that the patients were bridged to warfarin; therefore, their persistence was evaluated based on warfarin therapy. Persistence on therapy was assessed for 12 months using Kaplan-Meier rates, and unadjusted Cox proportional hazards models were used to compare the time to discontinuation between cohorts. Results: A total of 2,941 newly diagnosed patients with cancer who developed VTE and received anticoagulation in outpatient settings were identified. Of these, 97% received anticoagulation with either LMWH (n=735; 25%), LMWH/warfarin (n=550; 18.7%), warfarin (n=853; 29%), rivaroxaban (n=709; 24.1%). Mean age and gender were similar across treatment cohorts. Approximately 90% of the patients had diagnoses of solid tumors. Diagnoses for DVT, PE, and DVT/PE were 55%, 27%, and 18%, respectively, and were similar across cohorts. Treatments for cancers associated with very high VTE risk (stomach, pancreas, and brain) ranged from 15% in LMWH to 6% in rivaroxaban cohorts, while high VTE risk (lung, lymphoma, gynecologic, bladder, testicular, and renal) ranged from 39% in LMWH to 30% in warfarin and LMWH/warfarin cohorts. Around 75% (warfarin) to 58% (rivaroxaban) of the VTE cases were diagnosed in inpatient settings. The median treatment durations for LMWH, LMWH/warfarin, warfarin, and rivaroxaban users were 3.29, 7.76, 8.12, and 7.92 months, respectively. Kaplan-Meier rates of persistence to the initial therapy were 37%, 60%, 62%, and 61% at 6 months, and 21%, 37%, 34%, and 36% and at 12 months for the LMWH, LMWH/warfarin, warfarin and rivaroxaban cohorts, respectively (Figure 1). LMWH/warfarin, warfarin, and rivaroxaban users were significantly more likely to remain on their initial therapy compared to LMWH, with hazard ratios (HRs; 95% CI) of 0.38 (0.32-0.45), 0.40 (0.34-0.46), and 0.42 (0.36-0.50), respectively (all p-values <0.0001). The proportion of patients that switched from their initial treatment to another anticoagulation treatment was 22.9%, 8.9%, 7.3% and 4.7% in the LMWH, LMWH/warfarin, warfarin, and rivaroxaban cohorts, respectively. Conclusion: This real-world analysis showed that despite guidelines recommendations, warfarin and rivaroxaban are nearly equally utilized as LMWH for the treatment of cancer-associated thrombosis. LMWH was associated with significantly lower persistence and shorter duration of treatment than warfarin and rivaroxaban. More patients switched from LMWH to other anticoagulants compared to patients starting on warfarin or rivaroxaban treatments. Disclosures Khorana: sanofi: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria. McCrae:Janssen Scientific Affairs: Membership on an entity's Board of Directors or advisory committees. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Scientific Affairs: Research Funding. Nelson:Johnson & Johnson: Equity Ownership; Janssen Scientific Affairs: Employment. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Yannicelli:Janssen Scientific Affairs: Employment, Equity Ownership. Schein:Janssen Scientific Affairs, LLC: Employment.

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Improving Outcomes and Reducing Costs for Cancer Associated Thrombosis Using a Centralized Service: The Cleveland Clinic Experience

Blood ◽

10.1182/blood.v126.23.1122.1122 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1122-1122

Author(s):

Emma Rabinovich ◽

Shiva Shrotriya ◽

Keith R. McCrae ◽

John R. Bartholomew ◽

Bernard J. Silver ◽

...

Keyword(s):

Board Of Directors ◽

Cancer Patients ◽

Cleveland Clinic ◽

Clinical Service ◽

Advisory Committees ◽

Variation In Care ◽

Cancer Types ◽

The Mean ◽

Recurrent Vte ◽

Cancer Associated Thrombosis

Abstract Background: Venous thromboembolism (VTE) is a leading cause of mortality, morbidity, and hospitalization in cancer patients. Despite convincing evidence that treatment with low molecular weight heparin (LMWH) offers the best outcomes for patients with acute VTE, there exists a great variation in care, with up to 60% of patients in the United States not receiving LMWH. We instituted a centralized service for care of cancer patients with suspected deep venous thrombosis (DVT) and/or pulmonary embolism (PE) at Taussig Cancer Institute of the Cleveland Clinic in August 2014. We hypothesized that a cancer-associated thrombosis (CAT) clinical service that provides standardized management would reduce variation in care, and lower rates of recurrence, bleeding, and hospitalization in this patient population. Methods: We conducted a prospective cohort study of patients seen by the CAT clinical service. We collected data regarding demographics, cancer types, VTE characteristics, treatment recommendations, and outcomes in these patients. Outcome data included VTE recurrence, major or clinically relevant nonmajor bleeding according to International Society on Thrombosis and Haemostasis definitions, hospitalization, and mortality. Results: The study population comprised 221 patients with suspected VTE seen by the CAT clinical service between August 2014 and July 2015. Patients were 51% female, with a median age of 62±13 years. Hematologic malignancies (23%, N=50 of 221), breast cancer (10%, N=22 of 221), brain cancer (10%, N=22 of 221), pancreatic cancer (10%, N=21 of 221), and lung cancer (10%, N=21 of 221) were among the most commonly observed cancer types. VTE was diagnosed in 51 patients (23%, N=51 of 221). Of these, 39 patients (76%) had DVT, 5 (10%) had PE, and 7 (14%) had both. Hospitalization for VTE was necessary in only 24% (N=13 of 51) of cases. The mean and median costs of hospitalization for VTE (all costs) were US$7,656 and US$2,842, respectively, whereas the mean and median costs of outpatient treatment of VTE were US$1,160 and US$824 respectively. Initial treatment for 94% (N=48 of 51) of patients was with enoxaparin. Other treatments included warfarin (2%, N=1 of 51), heparin (2%, N=1 of 51), and apixaban (2%, N=1 of 51). Of patients started on enoxaparin, 71% (N=34 of 48) remained on enoxaparin for the duration of their care, while 16% (N=8 of 48) were bridged to warfarin after a median of 9 days and 10% (N=5 of 48) were taken off anticoagulants due to bleeding or other considerations. Common causes for transitioning to warfarin were financial considerations (50%, N=4 of 8), patient preference (38%, N=3 of 8), and poor renal function (13%, N=1 of 8). VTE recurred in 14% (N=7 of 51) of patients with a median follow-up of 3.5 months. Recurrences occurred in 9% (N=3 of 34) of patients on enoxaparin monotherapy, in 22 % (N=2 of 9) of patients started on or bridged to warfarin and 33% (N=2 of 6) of patients taken off anticoagulation. A total of 10 recurrent VTE events occurred in 7 patients. Of these, 4 required hospitalization. The mean and median costs of hospitalization for recurrence (all costs) were US$19,528 and US$18,627, respectively. The mean and median costs of initial outpatient care (excluding drug costs) for recurrent VTE were US$998 and US$728, respectively. Major or clinically relevant bleeding was seen in 14% (N=7 of 51) of patients on anticoagulants, with 86% (N=6 of 7) requiring hospitalization. The risk of bleeding in patients on enoxaparin (15%, N=5 of 34) was similar to that seen in patients who bridged to warfarin (14%, N=1 of 8). The mean and median costs of hospitalization for bleeding (all costs) were US$11,754 and US$8,806 respectively. Conclusions: Centralizing care of CAT reduces treatment variation and appears to improve patient related outcomes including the need for VTE-related hospitalizations and recurrent VTE. Substantial cost savings can be achieved by avoiding unnecessary hospitalization for appropriate patients and by reducing recurrence and bleeding rates with appropriate therapy. Disclosures McCrae: Halozyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Syntimmune: Consultancy; Momenta: Consultancy. Bartholomew:Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy. Khorana:Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Leo Pharma: 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; Daiichi Sankyo: Consultancy, Honoraria; sanofi: Consultancy, Honoraria.

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Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽

10.1182/blood-2020-139431 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 48-49

Author(s):

Samantha Ferrari ◽

Chiara Pagani ◽

Mariella D'Adda ◽

Nicola Bianchetti ◽

Annamaria Pelizzari ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

High Risk ◽

Board Of Directors ◽

Advisory Board ◽

Advisory Committees ◽

Risk Status ◽

History Of ◽

Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=<0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Blood ◽

10.1182/blood-2019-128807 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3433-3433

Author(s):

Caitlin Siebenaller ◽

Madeline Waldron ◽

Kelly Gaffney ◽

Brian P. Hobbs ◽

Ran Zhao ◽

...

Keyword(s):

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Smoking Status ◽

Consolidation Therapy ◽

Peripheral Vascular ◽

Consolidation Chemotherapy ◽

Advisory Committees ◽

History Of ◽

Acute Myeloid

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

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Incidence of VTE Among Patients with a Cancer Diagnosis in Oklahoma County

Blood ◽

10.1182/blood-2019-130604 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3463-3463

Author(s):

Micah Denay McCumber ◽

Aaron Mark Wendelboe ◽

Janis Campbell ◽

Kai Ding ◽

Michele G Beckman ◽

...

Keyword(s):

Native Americans ◽

Cancer Diagnosis ◽

Incidence Rates ◽

Cancer Type ◽

Surveillance Period ◽

Increased Risk ◽

History Of ◽

Race Ethnicity ◽

History Of Cancer ◽

Active Cancer

Background: Patients with cancer are at elevated risk for venous thromboembolism (VTE). Active cancer contributes a 4-7 fold increased risk for VTE; however, the incidence of VTE stratified by subpopulations of patients diagnosed with cancer, especially race/ethnicity, is uncertain. Objective: Describe the incidence of VTE among adult patients (age ≥ 18 years) with a cancer diagnosis in Oklahoma County, OK according to age, gender, race, and cancer type. Methods: In collaboration with the Centers for Disease Control and Prevention, we established a population-based surveillance system for VTE in Oklahoma County, OK between April 1, 2012-March 31, 2014 to estimate the incidences of first-time and recurrent VTE events. The Commissioner of Health made VTE a reportable condition and delegated surveillance-related responsibilities to the University of Oklahoma, College of Public Health. Active surveillance involved reviewing imaging studies (e.g., chest computed tomography and compression ultrasounds of the extremities) from all inpatient and outpatient facilities in the county and collecting demographic, treatment and risk factor data on all VTE case-patients. Patients were linked to the Oklahoma Central Cancer Registry. Any patient with a cancer diagnosis since 1997, excluding basal or squamous cell carcinoma, were included in the population-at-risk. Active cancer was defined as metastatic or a diagnosis ≤6 months before their VTE diagnosis. Poisson regression was used to estimate incidence rates (IRs) and 95% confidence intervals (CIs), which are reported per 1,000 person years (PY). Estimates with <10 events were suppressed. Results: Among all patients aged ≥18 years with a cancer diagnosis since 1997, 1.5% (n = 881) had a VTE event during the 2-year surveillance period. The overall annual age-adjusted incidence of VTE among those with cancer was 6.8 per 1,000 PY (95% CI: 5.81, 7.95). The demographic-specific incidence rates are summarized in Table 1. The VTE incidence did not significantly differ by sex. When stratified by age, annual VTE incidence was similar among those aged 18-39 years (6.1/1,000 PY, 95% CI: 4.35, 8.61), 40-59 years (6.2/1,000 PY, 95% CI: 5.4, 7.14), and 60-79 years (7.2/1,000 PY, 95% CI: 6.55, 7.90), however, the incidence was significantly higher (p<0.05) in those aged 80+ years (10.1/1,000 PY, 95% CI: 8.77, 11.61). When patients with a cancer diagnosis were stratified by race/ethnicity, non-Hispanic blacks had the highest VTE incidence (11.7/1,000 PY, 95% CI: 10.00, 13.59), followed by Hispanics (8.0/1,000 PY, 95% CI: 5.66, 11.44), non-Hispanic whites (6.9/1,000 PY, 95% CI: 6.41, 7.48), other non-Hispanic/unknown (5.8/1,000 PY, 95% CI: 3.45, 9.85), and non-Hispanic Native Americans (2.6/1,000 PY, 95% CI: 1.39, 4.79). VTE incidence was highest among those with active cancer or a history of cancer within the past three years, after which it appeared to decrease. When stratified by primary cancer type, VTE incidence was highest among those with brain cancer (16.6/1,000 PY, 95% CI: 11.06, 25.04) and lowest among those with prostate cancer (5.2/1,000 PY, 95% CI: 4.20, 6.44). As shown in Table 2, when stratified by cancer type, the incidence of VTE was higher (non-overlapping CIs) among those with active cancer compared to those with a history of cancer >6 months for several tumor types. Discussion: The incidence of VTE among those with cancer differs by race/ethnicity, with non-Hispanic blacks bearing the highest burden of disease. The risk of VTE persists and is particularly elevated up to three years after a cancer diagnosis. Disclosures Raskob: Eli Lilly: Consultancy; Pfizer: Consultancy, Honoraria; Portola: Consultancy; Novartis: Consultancy; BMS: Consultancy, Honoraria; Janssen R&D, LLC: Consultancy, Honoraria; Tetherex: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Anthos: Consultancy; Bayer Healthcare: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy.

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BCX9930, a Potent, Selective, Oral Factor D Inhibitor, Demonstrates Proof-of-Concept As Monotherapy in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Blood ◽

10.1182/blood-2020-138838 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-15

Author(s):

Austin Kulasekararaj ◽

Jacques Le Roux Malherbe ◽

Andrew McDonald ◽

Melanie Cornpropst ◽

Phil Collis ◽

...

Keyword(s):

South Africa ◽

Board Of Directors ◽

Research Funding ◽

Total Bilirubin ◽

Proof Of Concept ◽

Advisory Committees ◽

Clone Size ◽

The Past ◽

History Of ◽

Pre Treatment

INTRODUCTION: PNH, a rare, chronic, life-threatening disease, is characterized by hemolytic anemia due to uncontrolled activity of the complement alternative pathway (AP), bone marrow failure, and thrombosis. Inhibition of C5 by intravenously administered eculizumab and ravulizumab reduces intravascular hemolysis, but PNH red blood cells (RBCs) become opsonized and susceptible to extravascular hemolysis (Risitano et al, Blood 2009). Only approximately half of PNH patients become transfusion independent with eculizumab treatment (Hillmen et al, NEJM 2006). BCX9930 is a potent, selective, orally administered inhibitor of complement factor D. Inhibition of factor D may prevent both intravascular and extravascular hemolysis in PNH. In healthy subjects, BCX9930 showed linear pharmacokinetics and dose-related AP suppression, and was safe and generally well-tolerated over a wide dose range. Here we describe safety and laboratory data establishing proof-of-concept for BCX9930 monotherapy in PNH patients in Study BCX9930-101 (NCT04330534). METHODS: Ongoing Study BCX9930-101 includes an open-label, dose-ranging evaluation of BCX9930 in PNH subjects who may either be naïve to C5 inhibitors (and receive BCX9930 as monotherapy) or have an incomplete treatment response to eculizumab or ravulizumab (with BCX9930 added to existing treatment). Up to 4 sequential cohorts each use a forced titration design for the first 28 days (Figure 1). Subjects enrolled in South Africa can participate in an individualized 48-week extension if they derive benefit at Day 28. Clinical benefit from BCX9930 is evaluated using laboratory monitoring and symptom assessment. Safety and tolerability are evaluated via clinical and laboratory monitoring, causality of adverse events is assessed by investigators, and the study is overseen by an independent Data Monitoring Committee. Data from Cohort 1 through 28 days is reported; data from the extension and subsequent cohorts will be subsequently summarized as available. RESULTS: To date, four C5 inhibitor naïve PNH subjects in South Africa have enrolled in Cohort 1. These subjects had PNH for a median of 4.5 years; 2 subjects had a history of transfusions in the past year; 1 subject each had a history of aplastic anemia or major thrombosis. Pre-treatment lactate dehydrogenase (LDH), total bilirubin, hemoglobin (Hb), reticulocyte count, and RBC PNH Type III clone size ranged from 3.7-11.1 × ULN, 0.61-3.3 mg/dL, 6.1-11.6 g/dL, 0.13-0.29 × 106/µL, and 41.4%-88.6% respectively. Treatment over 28 days with 50 mg twice daily (BID; Days 1-14) and 100 mg BID (Days 15-28) of BCX9930 produced dose-dependent, clinically meaningful improvements across hemolysis biomarkers (Figure 2). Decreases were observed in LDH (4/4), reticulocytes (4/4), and total bilirubin (2/2 subjects with elevated pre-treatment values). Increases were observed in Hb (3/4) and PNH RBC clone size (4/4). One subject showed an initial response to BCX9930 50 mg BID, followed by worsening indicators of hemolysis temporally associated with an upper respiratory tract infection (URTI; onset on Day 7). With an increase in dose to 100 mg BID and resolution of the URTI, LDH and reticulocytes fell and Hb rose. All four subjects reported one or more PNH-associated symptoms, including hemoglobinuria, jaundice, fatigue, erectile dysfunction, headache and abdominal pain, prior to enrollment. With the exception of one subject with persistent hemoglobinuria, all symptoms resolved by Day 28 on BCX9930. Three subjects experienced moderate headache that resolved in < 3 days after initiating BCX9930. One subject developed a rash during treatment with amoxicillin for an URTI; the rash resolved while continuing BCX9930 dosing. One subject on concomitant chronic corticosteroids and azathioprine had an unrelated fatal serious adverse event of disseminated varicella during the study extension. Based on review of safety data, Cohort 2 opened at doses of 200 mg BID and 400 mg BID and, in the 3 subjects who continued into the extension, the dose was titrated to ≥ 200 mg BID. CONCLUSIONS: Oral BCX9930 elicited rapid changes in laboratory parameters indicative of reduced hemolysis and clinical benefit and was safe and generally well-tolerated over a 28-day dosing interval. These interim results establish proof of concept for monotherapy with BCX9930 in the treatment of C5-inhibitor naïve PNH patients and support evaluation of higher doses. Disclosures Kulasekararaj: Alexion:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Ra Pharma:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;BioCryst Pharmaceuticals, Inc.:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Apellis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Celgene:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau.Malherbe:Key Oncologics:Honoraria, Other: Conference sponsor;Novartis:Other: Conference sponsor;Astellas:Honoraria, Other: Conference sponsor;Takeda:Consultancy;Acino:Honoraria;Shire:Other: Conference sponsor;BioCryst Pharmaceuticals, Inc.:Consultancy;Janssen:Consultancy, Honoraria, Other: Conference sponsor;Roche:Honoraria, Other: Conference sponsor.McDonald:venetoclax advisory board in South Africa (in CLL context):Consultancy;Alberts Cellular Therapy:Current Employment.Cornpropst:BioCryst Pharmaceuticals, Inc.:Current Employment.Collis:BioCryst Pharmaceuticals, Inc.:Current Employment.Davidson:BioCryst Pharmaceuticals, Inc.:Current Employment.Chen:BioCryst Pharmaceuticals, Inc.:Current Employment.Tower:BioCryst Pharmaceuticals, Inc.:Current Employment.Gesty-Palmer:BioCryst Pharmaceuticals, Inc.:Current equity holder in publicly-traded company, Ended employment in the past 24 months.Sheridan:BioCryst Pharmaceuticals, Inc.:Current Employment.Risitano:Alexion:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Alnylam:Research Funding;Novartis:Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Pfizer:Speakers Bureau;Achillion:Membership on an entity's Board of Directors or advisory committees;Apellis:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Biocryst:Membership on an entity's Board of Directors or advisory committees;RA pharma:Research Funding;Amyndas:Consultancy;Samsung:Membership on an entity's Board of Directors or advisory committees;Roche:Membership on an entity's Board of Directors or advisory committees;Jazz:Speakers Bureau.

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Older Age and Increased Neutrophil-to-Lymphocyte Ratio (NLR) Are Predictors of Mortality in a Multiethnic Urban Cohort of Hematologic Neoplasms and COVID-19 Patients

Blood ◽

10.1182/blood-2020-138842 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Angelica D'Aiello ◽

Sumaira Zareef ◽

Kith Pradhan ◽

Amanda Lombardo ◽

Fariha Khatun ◽

...

Keyword(s):

Cancer Treatment ◽

Board Of Directors ◽

Median Time ◽

Lymphocyte Count ◽

Research Funding ◽

Hematologic Neoplasms ◽

Private Company ◽

Advisory Committees ◽

Treatment Status ◽

Race Ethnicity

Introduction: We sought to compare outcomes among patients with hematologic neoplasms diagnosed with COVID-19 infection in a multiethnic urban academic medical center. Methods: A retrospective analysis of patients with hematologic neoplasms diagnosed with COVID-19 from March 17th to June 8th2020 was conducted. Subjects included were censored at last point of contact. Variables collected included age, gender, race/ethnicity, hematologic diagnosis, cancer treatment status, baseline and follow-up COVID-19 testing, neutrophil count, and lymphocyte count at time of diagnosis. Associations between hematologic diagnosis, cancer treatment status, age, gender, race/ethnicity, neutrophil-to-lymphocyte ratio (NLR), and overall survival (OS) were assessed using the Kaplan-Meier method with logrank test. Results: A total of 102 subjects with hematologic neoplasms and COVID-19 infection treated in Montefiore Health system were identified (Table 1). Thirty-nine (38%) subjects were undergoing active treatment, including 17 (16%) receiving conventional chemotherapy agents, 12 (12%) targeted therapy, and 10 (10%) combination therapy. Of those subjects, twenty (50%) experienced delay or discontinuation of treatment due to COVID-19 infection. Four subjects (4%) showed persistent infection by PCR at median duration of 25.1 days after initial diagnosis. Ten subjects (9.8%) showed clearance of the virus by PCR with median time-to-clearance of 51.8 days. Of 9 subjects with serologic testing, 8 tested positive for COVID-19 IgG antibody at median time of 62 days after initial COVID-19 diagnosis. Forty-seven (47%) subjects expired as a result of COVID-19 disease at the time of analysis. Disease type, treatment status, race/ethnicity, age, and gender showed no significant association with mortality. Patients older than 70 had worse outcomes than the younger population (p = 0.0082). Median neutrophil and lymphocyte count at time of diagnosis was 4500 and 900, respectively. NLR greater than 9 was associated with worse survival when compared to NLR less than 9 (p=0.0067). Conclusions: COVID-19 infection has adverse effects on patients with hematological neoplasms. Subjects older than 70 years had a significantly worse prognosis. Notably, subjects actively being treated with chemotherapy did not have worse outcomes than those not being treated in our cohort, supporting the notion than active COVID-19 infection per se should not result in treatment delays. In addition, high NLR correlates with worsened survival, suggesting that this could be a potential prognostic factor for COVID-19 mortality in the hematologic neoplasms population. Disclosures Steidl: Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Research Funding; Pieris Pharmaceuticals: Consultancy; Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Verma:stelexis: Current equity holder in private company; BMS: Consultancy, Research Funding; Medpacto: Research Funding; Janssen: Research Funding; acceleron: Consultancy, Honoraria.

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Long-Term Survival Benefit of Eculizumab Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from the International PNH Registry

Blood ◽

10.1182/blood-2021-153560 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2188-2188

Author(s):

Louis Terriou ◽

Christopher J. Patriquin ◽

Morag Griffin ◽

Jong Wook Lee ◽

Philippe Gustovic ◽

...

Keyword(s):

Rare Disease ◽

Board Of Directors ◽

Survival Probability ◽

Advisory Committees ◽

Term Survival ◽

Treatment Status ◽

History Of ◽

Baseline Characteristics

Abstract Background Eculizumab, the first C5 inhibitor approved for paroxysmal nocturnal hemoglobinuria (PNH), transformed PNH treatment by improving survival to that of an age- and sex- matched general population. Previous analyses demonstrating the survival benefit of eculizumab in patients with PNH leveraged historical data and were limited by small patient numbers and short follow-up durations; few evaluated survival of patients receiving eculizumab compared with untreated patients. The objective of the current analysis was to describe the baseline characteristics and overall survival of a large international cohort of eculizumab-treated patients compared with a contemporaneous untreated cohort using data from the prospective, observational International PNH Registry (NCT01374360). Methods Data from patients enrolled in the Registry after March 16, 2007 with complete information for birth date, sex, enrollment date, and treatment status were included (database cut-off, April 12, 2021). Ever-treated patients were those who received eculizumab for a minimum treatment period of 35 days while enrolled in the Registry; never-treated patients did not receive eculizumab at any time before or during Registry participation. Univariate and multivariate analyses were performed using a Cox proportional hazards that incorporated the following parameters at baseline as covariates: treatment status, presence of high disease activity (HDA), age, sex, history of bone marrow failure (BMF), history of thrombotic events (TE), transfusion dependence, and estimated glomerular filtration rate ≤60 mL/min/1.73 m 2. HDA was defined as lactate dehydrogenase (LDH) ratio ≥1.5 × upper limit of normal (ULN) and ≥1 of the following: history of major adverse vascular events (including TE); anemia (hemoglobin <10 g/dL), or physician-documented abdominal pain, dyspnea, dysphagia, fatigue, hemoglobinuria, or erectile dysfunction at any time before and including baseline. Baseline was defined as the date of eculizumab treatment initiation (ever-treated patients) or date of Registry enrollment (never-treated patients). Survival time was analyzed using a left-truncation approach that mapped time in patients' survival based on disease start date, defined as the earliest date of first-reported PNH diagnosis, PNH symptom, or first consistent flow cytometry result. Results Baseline characteristics of the 4627 patients included in the analysis (mean [SD] age at disease start, 40.2 [18.71] years; 53% female; 75% white) were comparable between the ever-treated and never-treated groups (n=1892 and n=2735, respectively). Compared with never-treated patients, more ever-treated patients had LDH ≥1.5 × ULN (90% vs 35%), and fewer had <10% PNH granulocytes (3% vs 57%) or history of BMF (45% vs 76%). The univariate Cox proportional hazard ratio (HR) for mortality in ever-treated vs never-treated patients was 0.48 (95% CI, 0.39-0.60; P<0.0001), indicating a 52% increase in survival in the treated group (Table). Among ever-treated patients, those with HDA at baseline experienced the largest reduction in mortality risk (HR [95% CI], 0.46 [0.33-0.64]; n=174); however, decreased mortality was also evident in ever-treated patients without HDA (HR, 0.65 [0.39-1.10]; n=212) or with unknown HDA status (HR, 0.50 [0.32-0.76; n=120) at baseline. Overall survival probability by treatment status was consistently greater in ever-treated vs never-treated patients through 20 years of follow-up; survival probability at 20 years was 82% (ever-treated) vs 69% (never-treated). Although long-term survival probability was greatest throughout follow-up in ever-treated patients with HDA at baseline, increased survival among ever-treated patients was evident in all 3 HDA status groups (Figure). Conclusion In this analysis of Registry data, treatment with the C5 inhibitor eculizumab improved patient survival compared with a never-treated cohort at a comparable time point in their disease course. Covariates were assessed at baseline only and competing risks and time on treatment were not controlled for, which are potential limitations. Survival benefits conferred by eculizumab treatment were observed regardless of HDA status at baseline, were more pronounced in treated patients with HDA vs those without HDA, and were maintained through 2 decades of real-world follow-up. Figure 1 Figure 1. Disclosures Terriou: Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patriquin: Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Speakers Bureau; Biocryst: Honoraria; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Griffin: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees; BioCryst Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis: Other: Educational grant support. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gustovic: Alexion, AstraZeneca Rare Disease: Current Employment. Patel: Alexion, AstraZeneca Rare Disease: Current Employment. Szer: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Prevail Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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