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In: The American Journal of Human Genetics, Elsevier BV, Vol. 97, No. 4 ( 2015-10), p. 512-520

Type of Medium: Online Resource

ISSN: 0002-9297

URL: Article

DOI: 10.1016/j.ajhg.2015.08.008

Language: English

Publisher: Elsevier BV

Publication Date: 2015

detail.hit.zdb_id: 1473813-2

SSG: 12

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e18753-e18753

Abstract: e18753 Background: Cancer patients are more susceptible to developing severe disease associated with SARS-CoV-2 infection. Herein, data from a high-volume cancer center is presented highlighting risk factors associated with hospitalization with COVID-19 disease. Methods: Cancer patients in the Levine Cancer Institute COVID19 database who were tested for SARS-CoV-2 due to clinical illness from March 1, 2020 to October 29, 2020 with 90 days follow-up are described here. Patients’ demographic and clinical information were retrospectively entered into a REDCap database from chart reviews. Differences in distributions were identified between hospitalized and non-hospitalized patients using the chi-squared test with uni- and multivariable logistic regression models. Statistical significance was set at p 〈 0.05. Results: 228 patients with SARS-CoV-2 infection were identified, of whom 103 (45%) were hospitalized. Median age was 63 years (range 28-95). Race distribution for infection showed White 65%, followed by Black 26.8% and Hispanic ethnicity 16.7% , with a similar distribution for hospital admission. Median length of stay was 10 days (range 1-91) with no readmissions within 90 days. The most common underlying malignancies were breast (29.8%), hematologic (21.1%) and genitourinary (12.3%). The most common preexisting conditions included hypertension (55.7%), diabetes (27.2%) and cardiac disease (3.9%). The most common presenting symptoms were cough (50.2%), fever (38.4%), fatigue (37.8%) and shortness of breath (36.4%). Maximum oxygen requirements for hospitalized patients were ambient air (34%), nasal canula (34%), high/medium flow nasal canula (10%), non-invasive ventilation (13%) and mechanical ventilation (10%). Case fatality rate was 10% with diagnosis of COVID-19, including 21.4% of those admitted to the hospital and 51.7% of those admitted to the ICU. Univariable logistic regression analysis showed that age, sex, prior chemotherapy, upper gastrointestinal cancers, hematologic cancers, number of medical conditions, cardiac disease, chronic lung diseases, hypertension, and diabetes increased risk of hospitalization. Table shows results of multivariate analysis. Conclusions: The COVID-19 pandemic has caused high case fatality rates in our cancer patients. We identified age, cardiac disease, hematologic malignancy and receipt of chemotherapy within 4 weeks of diagnosis as risk factors for hospitalization. These data may help in prioritizing early intervention in vulnerable subgroups to improve survival outcomes. [Table: see text]

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2021.39.15_suppl.e18753

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2021

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e19080-e19080

Abstract: e19080 Background: Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production. Most patients (pts) harbor a JAK2 mutation and must have erythrocytosis or elevated red cell mass for diagnosis (DX). Pts are at increased risk of thrombosis. Current treatments include aspirin, therapeutic phlebotomy (TP), and cytoreductive therapy such as hydroxyurea (HU). In 2014, based on the RESPONSE study, ruxolitinib (rux), a selective JAK inhibitor, was approved for second line treatment after intolerance or inadequate response to HU. A recent real-world analysis of rux in PV showed durable hematocrit (HCT) control and decreased need for TP (Coltoff 2020). Despite emerging clinical reports, real-world data on HCT control, dose adjustment, and thrombotic risk with rux are extremely limited. Methods: A retrospective chart review from three centers was performed to evaluate PV pts treated with rux between Dec 2014 and Dec 2019. Pts age 〈 18 at rux start, who received rux through investigational studies, and/or who had myelofibrosis were excluded. Data cutoff was May 30, 2022. Results: 69 patients were identified. Median time from PV DX to rux start was 4.4 yrs (range 0.1 to 40.2), and median follow-up from start of rux was 3.3 yrs (range 0.1 to 6.3). Pt characteristics: 37 (54%) Male, 59 pts (86%) White, 4 (6%) Black, and 64 (93%) Non-Hispanic. The most common reasons for starting rux were HU intolerance (46%), uncontrolled platelet count (28%), and symptom burden (19%). Median time on rux was 2.4 yrs (range 0.1 to 6.3); 43 pts (62%) remained on rux at data cutoff. A total of 6 pts (9%) received less than 3 months of rux before discontinuation, 8 pts (12%) received less than 6 months of rux. 41% pts (27/66), did not have HCT control (HCT 〈 45%) within 1 month prior to rux start. Of evaluable pts, HCT control rates at 3 and 6 months were 88% (52/59) and 89% (47/53) respectively. Phlebotomy frequency in the 3-month periods before and after rux start were known for 48 pts; 21 (44%) experienced a decrease in phlebotomies within 3 months after initiation of rux, 20 (42%) remained stable, and 7 (16%) saw an increase (ranging from +1 to +3). Twelve pts (17%) required dose reductions/suspensions due to cytopenias. One pt experienced an acute pulmonary embolism while on rux (4.4 yrs after rux initiation). The pt was diagnosed with T cell lymphoma while on rux and the thrombotic event was attributed to lymphoma. This pt achieved HCT control on rux at 3 and 6 months. No arterial thromboses were observed. Conclusions: In this real-world analysis, rux was highly effective in controlling HCT in the vast majority of PV pts by 3 and 6 months. PV pts treated with rux rarely developed thrombosis. Rux was well tolerated, and few patients required dose reduction or discontinuation. [Table: see text]

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2023.41.16_suppl.e19080

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2023

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 40-41

Abstract: Background and Rationale: Relapse remains the leading cause of treatment failure for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic bone marrow transplantation (BMT). Although the risk depends on parameters such as age and conditioning intensity, relapse is experienced by 30-50% of patients after conventional BMT in high-risk AML/MDS. Initial safety and post-BMT relapse risk reduction results were reported from a phase I study of haploidentical (haplo) donor-derived natural killer (NK) cells expanded ex vivo on feeder cells expressing IL-21 and 4-1BBL (FC21-NK) in conjunction with haploBMT. Of 13 patients with high-risk myeloid malignancies treated with FC21-NK cells, no infusion reactions or dose-limiting toxicities occurred and only 1 patient, treated at the lowest dose of 1×105 cells/kg, relapsed (Ciurea, Blood, 2017). This experience supports investigation of K-NK002, a product derived from haploidentical donor NK cells and expanded ex vivo in a feeder cell-free system using plasma membrane (PM21) particles bearing membrane-bound IL-21 and 4-1BBL. We used contemporary data from the Center for International Blood and Marrow Transplant Research registry to determine baseline relapse rates that informed the statistical design. K-NK002 will be given in the peri-transplant period to test the hypothesis that haploidentical NK cells can mediate an effective anti-leukemia response. Trial Design and Methods: BMT CTN 1803 is a phase II, single-arm, open-label, multicenter trial designed to investigate the safety and efficacy of K-NK002 for the treatment of patients with high-risk AML or MDS undergoing haploBMT (NCT04395092). An initial 6 patient safety run-in phase will precede enrollment into the full study of approximately 60 patients. Major inclusion criteria of patients and donors are listed in Table 1. Production of the haploidentical donor NK-cells is completed prior to the planned haploBMT. BMT conditioning will consist of 140 mg/m2 (100 mg/m2 for patients ≥60 years old) melphalan on Day -7; 40 mg/m2 fludarabine on Days -7, -6, -5, and -4; and 2 Gy of total body irradiation on Day -3. Donor bone marrow will be harvested and given on Day 0. Three doses of K-NK002 (1×108 NK cells/kg) will be administered IV on Days -2, +7, and +28, relative to the haploBMT. Graft-versus-host disease (GVHD) prophylaxis consists of post-transplantation cyclophosphamide with tacrolimus and mycophenolate mofetil. The primary endpoint is cumulative incidence of relapse at 1 year post haploBMT in patients receiving at least 1 infusion of K-NK002. Secondary endpoints are safety and tolerability of K-NK002; overall survival; non-relapse mortality; relapse-free survival; GVHD-free survival; cumulative incidence of acute GVHD and chronic GVHD; hematologic recovery; donor-cell engraftment; primary and secondary graft failure; overall incidence of toxicity; and cumulative incidence of infections including cytomegalovirus re-activation and symptomatic BK virus hemorrhagic cystitis. Exploratory endpoints are systemic immunosuppression-free survival; immune reconstitution at Days 28, 100, and 365 post haploBMT; proportion of patients with detectable minimal residual disease at Days 28 and 100 post haploBMT; feasibility of administering the planned K-NK002 doses; and impact of NK-cell alloreactivity on relapse and survival. Disclosures Bejanyan: Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees. Devine:Magenta Therapeutics: Consultancy. Luznik:WindMil Therapeutics: Patents & Royalties: Patent holder; Genentech: Research Funding; Merck: Research Funding, Speakers Bureau; AbbVie: Consultancy. Sandler:Kiadis Pharma: Current Employment. Krakow:HighPass Bio: Research Funding. Fitzgerald:Kiadis Pharma: Current Employment. Tracey:Kiadis Pharma: Current Employment. Champlin:DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties; Actinium: Consultancy; Johnson and Johnson: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; Genzyme: Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-134408

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2099-2099

Abstract: Background: Financial Toxicity (FT) is increasingly recognized as a major contributor to morbidity and mortality in a variety of cancers. Previous research has demonstrated patients with myeloproliferative neoplasms (MPNs) exhibit a substantial comorbidity burden and have an increased risk of mortality. The purpose of this study was to define rates of FT and the implications on morbidity and mortality in this population using patient reported data. Methods: All patients seen at the Levine Cancer Institute, a tertiary hospital-based specialty practice, were surveyed prior to their visit over a six-month period. All patients were aged ≥18 years and diagnosed with Philadelphia chromosome−negative classical MPNs including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 4 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Patient disease and treatment characteristics were summarized with frequencies and proportions for categorical variables and medians and ranges for continuous variables. Correlation of numerical FT scores with PROMIS scores was assessed with Pearson correlation coefficients and ANOVA regression. Additionally, model selection was carried out using logistic regression to identify factors impacting the incidence of financial toxicity (where FT score 〈 =4). Kaplan Meier methods were used to estimate overall survival distributions and log rank tests were used to compare between groups. Results: A total of 51 patients were surveyed. Disease type consisted of 45.1% MF, 31.4% PV, and 23.5% ET. Median age was 62 years. Most patients were high risk by disease specific scoring systems (58.8%), Caucasian (82.4%), and had commercial insurance (56.9%). Median distance from the clinic was 21 miles and median time from diagnosis was 2.2 years. Of the 51 patients surveyed, 20 (39.2%) met the predefined definition of exhibiting severe FT. Lower FT scores (indicating a higher degree of FT) were associated with lower global physical (p 〈 .001) and mental (p 〈 .002) scores by the PROMIS measures (Figure 1). There was no statistically significant difference in survival between patients with FT scores 〉 4 compared to patients with FT scores 〈 =4; however, there was a trend toward decreased survival in those with lower FT scores. The rate of mortality in those with FT score ≤4 was 15.0% compared to 3.2% in those with FT score 〉 4 (p =.287). There also appeared to be a separation of the survival curves when looking at both time from diagnosis and time from survey administration (Figures 2 and 3). Age, race, gender, insurance type, distance from the hospital, disease type, disease specific risk classification, medications utilized, and history of blood/marrow transplant were not found to be significantly different in the two groups. Conclusions: Patients with myeloproliferative neoplasms represent an extremely vulnerable population for financial toxicity with quantifiably increased distress related to this toxicity increasing morbidity and potentially mortality. These findings should be validated in a larger patient cohort and interventions devised to reduce financial distress. Disclosures Knight: Foundation for Financial Planning: Research Funding. Ai:InCyte: Speakers Bureau; Amgen: Speakers Bureau. Trivedi:Incyte: Speakers Bureau. Avalos:Best Practice-Br Med J: Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia; Juno: Membership on an entity's Board of Directors or advisory committees. Symanowski:Boston Biomedical: Membership on an entity's Board of Directors or advisory committees; Carsgen Therapeutics: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Immatics: Membership on an entity's Board of Directors or advisory committees. Grunwald:Amgen: Consultancy; Novartis: Research Funding; Genentech/Roche: Research Funding; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Agios: Consultancy; Incyte: Consultancy, Research Funding; Cardinal Health: Consultancy; Forma Therapeutics: Research Funding; Abbvie: Consultancy; Celgene: Consultancy; Merck: Consultancy; Medtronic: Equity Ownership; Janssen: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128858

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 25, No. 4 ( 2019-04), p. 785-790

Type of Medium: Online Resource

ISSN: 1083-8791

URL: Article

DOI: 10.1016/j.bbmt.2018.12.142

Language: English

Publisher: Elsevier BV

Publication Date: 2019

detail.hit.zdb_id: 3056525-X

detail.hit.zdb_id: 2057605-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 8048-8048

Abstract: 8048 Background: Coronavirus-2 has profound effects on patients (pts) with Multiple myeloma (MM). At the beginning of the pandemic, COVID-19 infection resulted an overall mortality around 54% (cook et al. BMJ 2020). Here, we report an updated morbidity and fatality for MM. Methods: After obtaining IRB approvals from each participating institute, retrospectively, between January 1, 2021 and August 30, 2021, we identified pts with MM and COVID-19 in two myeloma centers (Levine Cancer Institute (LCI) & the University of Kansas medical center (KUMC). Results: We identified 162 MM pts who had COVID-19 (LCI n=132, UKMC n=30), including 57% males, with median age of 64 years. Current or former smoking reported in 40% of pts. Most pts have associated comorbid conditions: hypertension (45%), hypogammaglobulinemia (32%), CKD (30%), DM (22%), obesity (16.6%), CHF (14%), and CAD (13.5%). Within 3 months prior to infection, treatment included immunomodulatory combinations in 35%, proteasome inhibitors in 28 %, and Daratumumab in 26.5%. Symptoms are summarized in table. 69% had Mild symptoms (no need for hospitalization), 20 % had moderate symptoms (requiring hospitalization), and 9.8% had severe symptoms (ICU level of care). The 18% of pts required oxygen: 6 pts required invasive oxygenation and 3 pts needed vasopressors. The 32% of pts had RRMM, 29.5% on maintenance, and 12% was getting induction. Regarding MM response: 〉 VGPR in 45% and PD in 18%. The 78 pts had ASCT prior to COVID-19 infection: only 3 pts 〈 1 year and 3 pts 〈 6 months. MM response or ASCT did not affect hospitalization or mortality.The case fatality rate (CFR) was 6%. In the univariate analysis, CKD, DM, HTN and hepatic dysfunction were associated with an increased risk of hospitalization. However, in multivariate analysis, only CKD, hepatic dysfunction, and Hypogammaglobulinemia significantly increased the risk of admission with only age and lymphopenia were associated with increased COVID-19 related fatatlity. Conclusions: With implementation of center-specific disease control measures and universal screening, pts might have lower case severity and fatality rate than was initially reported. [Table: see text]

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2022.40.16_suppl.8048

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2022

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 7033-7033

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2018.36.15_suppl.7033

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2018

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 40-41

Abstract: Background: MF patients (pts) can have significant disease-associated symptoms. Guidelines recommend evaluation of pts' symptom burdens and prognostic risk scores at clinic visits. The myeloproliferative neoplasm symptom assessment form total symptom score (MPN-SAF TSS) is a standardized system that evaluates 10 specific MPN-related symptoms on a scale of 1-10. Furthermore, the dynamic prognostic scoring system plus (DIPSS plus) has been validated as a risk stratification tool for MF pts at any point during the disease course. At our institution, leukemia physicians have created an MF pathway to guide practitioners throughout a large healthcare system with many locations. The pathway recommends MPN-SAF TSS and DIPSS plus risk score with clinic visits occurring every 3-6 months. Unfortunately, the traditional approach to obtaining the MPN-SAF TSS and DIPSS plus score is burdensome for many providers and pts. Moreover, a recent analysis (Verstovsek Ann Hematol 2020) demonstrates that risk prognostication is very often performed incorrectly. We designed a study to streamline workflow by incorporating our specialty pharmacy to assist in the completion of the MPN-SAF TSS and DIPSS plus score via telephone prior to clinic visits. We hypothesized that partnership between our physicians and the specialty pharmacy may benefit pts by increasing adherence to the MF pathway. Methods: This study is conducted in two parts, a retrospective and a prospective phase. A review 12 months prior to start of study was completed to gain historical insight on provider adherence to the MF pathway, with attention to MPN-SAF TSS and DIPSS plus. Then, a prospective study was designed to include new or established MF pts. Pts would be followed for 12 months after start of study. The pilot study was open only at our largest site, home to a subspecialty leukemia clinic where disease-specific physicians practice. For pts who enroll in the prospective study, specialty pharmacists complete both the MPN-SAF TSS and the DIPSS plus score ~3 months via phone prior to clinic visits. Calls for each pt are completed within 10 days of the pt's next visit. If the pharmacist is unable to reach the pt, the physician is notified via EMR message. Completed assessments are documented in the EMR. All enrolled pts are evaluated for MF pathway adherence during the study period. Results: We reviewed system-wide charts for 12 months prior to March 1, 2020 to assess if DIPSS and/or MPN SAF forms were documented for MF patients. 79 MF pts, treated by 32 physicians, were identified. Patients in remission after allogeneic stem cell transplantation were excluded. 36 pts (46%) had the MPN-SAF TSS completed and 53 pts (67%) had DIPSS plus performed at least once in the preceding 12 months. 45 pts, treated by 8 physicians, were followed primarily at the pilot site. 27 pts (60%) had MPN-SAF TSS documented and 38 (84%) had DIPSS Plus performed at least once in the preceding 12 months. The prospective study was initiated on March 1, 2020. As of July 15, 2020, 32 patients have been screened for enrollment by treating physicians. This includes 3 newly diagnosed patients not included in the retrospective analysis. 22 pts have had their initial assessments completed. 2 pts could not be reached, 1 of which died prior to the next clinic visit, 2 pts declined the study, and 6 pts had not yet had clinic visits. Of the 22 pts consented and contacted for the study, 100% had the MPN-SAF TSS and DIPSS Plus score documented with their first visit during the study period. To date 11 pts (of the initial 22) have undergone reevaluation; 100% had the MPN-SAF TSS and DIPSS Plus score documented with their 3-month follow-up visit. Conclusion: Many practicing clinicians perform MPN-SAF TSS and DIPSS plus scores for MF pts. However, there are lapses in the uptake of both. At our institution, the DIPSS plus score is performed more commonly than the MPN-SAF TSS. This early analysis suggests that a telemedicine approach and partnership between specialty pharmacy and physicians can optimize clinical workflow. With the initial success of this pilot, our program is expanding study enrollment to include regional clinics. Due to the COVID19 pandemic, there is now heightened interest in telemedicine practices. Preliminary data from this study suggest that a multidisciplinary approach incorporating telemedicine for MF pts provides an effective approach to measuring patient symptom burdens and assigning prognostic categories. Figure Disclosures Chojecki: Novartis: Other: Investigator Meeting Attendance; Incyte: Research Funding. Shah:Incyte: Speakers Bureau; Pharmacyclics: Speakers Bureau. Knight:Foundation for Financial Planning: Research Funding. Ai:Celgene: Speakers Bureau; Incyte: Speakers Bureau. Avalos:Best Practice-Br Med J: Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia; Juno: Membership on an entity's Board of Directors or advisory committees. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Grunwald:Janssen: Research Funding; Genentech/Roche: Research Funding; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Abbvie: Consultancy; Abbvie: Consultancy; Trovagene: Consultancy; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Agios: Consultancy; Janssen: Research Funding; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Premier: Consultancy; Merck: Consultancy; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding; Agios: Consultancy; Celgene: Consultancy; Celgene: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Premier: Consultancy; Astellas: Consultancy; Premier: Consultancy; Merck: Research Funding; Astellas: Consultancy; Merck: Consultancy; Genentech/Roche: Research Funding; Daiichi Sankyo: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Incyte: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136319

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 5-6

Abstract: Introduction: Letermovir is a terminase complex inhibitor that was recently approved for prevention of cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (HCT). Its favorable side effect profile makes it an attractive alternative to other anti-CMV agents. Nevertheless, its use may present other challenges secondary to enzyme induction, leading to clinically significant drug-drug interactions. Voriconazole is widely used for prophylaxis against invasive fungal infections in the setting of HCT. By virtue of its hepatic metabolism mediated by CYP2C19, the package insert recommends close monitoring of voriconazole trough concentration when given concomitantly with letermovir. The objective of this study was to characterize the extent of interaction between voriconazole and letermovir in allogeneic HCT recipients. The study was approved by the institutional review board. Methods: Patient selection and data collection: An institutional database was queried to identify patients who underwent allogeneic HCT and received antifungal prophylaxis with voriconazole from November 2018 through July 2020. Per the institutional standard operating procedure (SOP), patients initially received intravenous micafungin 50 mg daily which was switched to voriconazole when oral drug administration became feasible. The voriconazole prophylactic dose was guided by CYP2C19 phenotype. Rapid metabolizers (harboring the gain of function variantCYP2C19*17) received 300 mg twice daily whereas others received 200 mg twice daily. Further dose adjustment was warranted if trough concentration, measured at least 5 days after starting voriconazole, did not fall within target range of 1 to 5.5 mg/L. Patients at risk for CMV reactivation who underwent HCT after SOP revision (November 2019) received prophylaxis with letermovir 480 mg daily on day +6 post HCT. After a retrospective review of electronic medical records, HCT recipients were divided into two cohorts;cohort 1included patients who received letermovir prophylaxis whereascohort 2comprised those who did not. Data extracted from medical records included: demographics, hematological disorder, voriconazole dose and trough concentration, and date of letermovir initiation. Statistical analysis: The Student's t-test was used to compare mean voriconazole trough plasma concentration between cohorts 1 and 2. The chi-squared/Fisher's exact test was used to compare rate of subtherapeutic voriconazole trough concentration. Multivariate logistic regression analysis was performed to determine the association between letermovir use and subtherapeutic voriconazole concentration after adjusting for age, gender, race, weight and voriconazole dose. All statistical analyses were performed in SAS (version 9.4) Results: 64 patients were identified (23 in cohort 1 and 41 in cohort 2). Baseline characteristics were comparable except for age (62.0±8.7 years in cohort 1 vs. 58.0±12.2 years, p=0.01); 39% of patients in cohort 1 and 30% in cohort 2 received voriconazole 300 mg twice daily upfront for prophylaxis due to the rapid CYP2C19 metabolizer phenotype whereas the rest received voriconazole 200 mg twice daily (p=0.6). There was no significant difference in mean voriconazole trough plasma concentration (p=0.5) or frequency of subtherapeutic trough (p=0.16) between cohorts 1 and 2 (Figure 1). Multivariate logistic regression analysis indicated that letermovir prophylaxis had no impact on subtherapeutic voriconazole concentration (OR: 0.4, 95% CI: 0.1-1.4, p=0.1). In the subgroup of patients who received voriconazole at 300 mg twice daily, the rate of subtherapeutic concentration did not differ significantly between cohorts 1 and 2 (p=1.0), whereas a non-significant trend in rate of subtherapeutic voriconazole concentration was noted in subgroup of patients who received the 200 mg dose (p=0.1,Figure 2) Conclusions: Our single center experience suggests there may not be a significant interaction between voriconazole and letermovir. Notably, patients receiving the 300 mg dose upfront may not require an additional dose increase to achieve a voriconazole trough within the recommended range despite the concomitant use of letermovir. Our group is collaborating with other centers to corroborate these findings, particularly in patients receiving the standard voriconazole prophylactic dose of 200 mg. Disclosures Grunwald: Forma Therapeutics:Research Funding;Agios:Consultancy;Abbvie:Consultancy;Trovagene:Consultancy;Daiichi Sankyo:Consultancy;Astellas:Consultancy;Daiichi Sankyo:Consultancy;Trovagene:Consultancy;Trovagene:Consultancy;Premier:Consultancy;Astellas:Consultancy;Astellas:Consultancy;Genentech/Roche:Research Funding;Premier:Consultancy;Genentech/Roche:Research Funding;Genentech/Roche:Research Funding;Premier:Consultancy;Janssen:Research Funding;Merck:Consultancy;Forma Therapeutics:Research Funding;Incyte:Consultancy, Research Funding;Celgene:Consultancy;Incyte:Consultancy, Research Funding;Incyte:Consultancy, Research Funding;Pfizer:Consultancy;Celgene:Consultancy;Celgene:Consultancy;Cardinal Health:Consultancy;Merck:Research Funding;Daiichi Sankyo:Consultancy;Agios:Consultancy;Abbvie:Consultancy;Merck:Consultancy;Amgen:Consultancy;Merck:Consultancy;Amgen:Consultancy;Abbvie:Consultancy;Pfizer:Consultancy;Amgen:Consultancy;Pfizer:Consultancy;Agios:Consultancy;Cardinal Health:Consultancy;Forma Therapeutics:Research Funding;Cardinal Health:Consultancy;Janssen:Research Funding.Ai:Incyte:Speakers Bureau;Celgene:Speakers Bureau.Knight:Foundation for Financial Planning:Research Funding.Chojecki:Incyte:Research Funding;Novartis:Other: Investigator Meeting Attendance.Avalos:Juno:Membership on an entity's Board of Directors or advisory committees;Best Practice-Br Med J:Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia.Copelan:Amgen:Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-141124

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7