Rusfertide (PTG-300) Induction Therapy Rapidly Achieves Hematocrit Control in Polycythemia Vera Patients without the Need for Therapeutic Phlebotomy

Abstract Background. Polycythemia (PV) patients with hematocrit above 45% are at increased risk of thrombotic complications and are treated with phlebotomy and/or cytoreductive therapy to reach a hematocrit target below 45%. Rusfertide (PTG-300) is a peptidic mimetic of hepcidin that is being developed for treatment of polycythemia vera (PV). A Phase 2 trial has indicated that rusfertide is effective at reducing the number of phlebotomies and maintaining hematocrit below 45% without phlebotomy in PV patients who are either high-risk or low-risk, patients treated with cytoreductive therapy (hydroxyurea, interferon, ruxolitinib) and patients treated with phlebotomy alone (Kremyanskaya, ASH 2020). The current trial (PTG-300-08) tested the ability of rusfertide to normalize hematocrit in PV patients with elevated hematocrit without instituting phlebotomy treatment to normalize hematocrit to below 45% in PV patients without requiring phlebotomy and/or cytoreductive treatment. Methods. Eligible study subjects were diagnosed with PV (in accordance with the WHO 2016 criteria), had baseline hematocrit above 48%, and a history of 3 or more hematocrit values above 48% in the year prior to enrollment. High-risk and low-risk subjects treated with phlebotomy alone or with concurrent cytoreductive therapy were eligible. Rusfertide was added on to each subject's current therapy. The initial rusfertide dose was 40 mg administered subcutaneously twice weekly. When each subject's hematocrit was below 45%, the dosing schedule was changed to weekly and the rusfertide dose was adjusted to maintain hematocrit below 45%. Results. Sixteen subjects (12 male and 4 females) have been enrolled. The mean age is 56.1 years; the mean time since diagnosis is 3.74 years; 10 subjects are low risk PV; 12 subjects are receiving concurrent hydroxyurea and 4 subjects were not receiving cytoreductive therapy. Baseline values (mean, min-max) HCT (51.0%, 47.4 - 59), WBC (12,338/µL, 7,000 - 24,600), RBCs (5.9x10 6/µL, 4.3 - 7.6), platelets (486,500/µL, 242,000 - 904,000). All subjects had rapid decreases in hematocrit to below 45% without the use of phlebotomy (Figure 1a). Hematocrit levels remained well controlled after falling below 45% as investigators reduced rusfertide dose to maintenance once weekly regimen. Hemoglobin (Figure 1b) fell rapidly. Erythrocyte counts (Figure 1c) also fell rapidly, indicating that decreased hematocrit is due to decreased erythrocytosis. For the 11 subjects with adequate follow-up, the mean rate of absolute hematocrit decrease was 1.76% per week (median: 1.81%/week; min - max: 0.65 - 2.69%) and the mean time to reach goal hematocrit below 45% was 4.79 weeks (median: 4.14 weeks, min - max: 3.57 - 8.14). Eight subjects reported adverse events (AEs). Injection site reactions (ISRs) occurred in 7 subjects and were mild or moderate in severity. The most common ISRs were erythema (n=7), induration (n=5) and pruritis (n=2). Adverse events other than ISRs that occurred in 2 or more subjects were hypertension (n=2), pyrexia (n=2) and thrombocytosis (n=2). There were two serious adverse events (worsening migraine and pleuritic chest pain) and both were considered unrelated to rusfertide. Overall, rusfertide was well tolerated. Conclusions. This study demonstrates that induction therapy with twice weekly rusfertide administration was effective in rapidly achieving target hematocrit below 45% without phlebotomy in all PV patients which was then successfully maintained with weekly rusfertide treatment. Moreover, the twice weekly injections of rusfertide used to rapidly lower hematocrit levels were safe and well tolerated. Key words: Hepcidin, Hematocrit, Rusfertide, PTG-300, Polycythemia Vera, PV, Therapeutic Phlebotomy Figure 1 Figure 1. Disclosures Gupta: Protagonist Therapeutics: Current Employment. Valone: Protagonist Therapeutics: Consultancy, Current equity holder in publicly-traded company. Khanna: Protagonist: Current Employment, Current equity holder in publicly-traded company. Modi: Protagonist Therapeutics: Current Employment. Hoffman: Kartos Therapeutics, Inc.: Research Funding; Protagonist Therapeutics, Inc.: Consultancy; Novartis: Other: Data Safety Monitoring Board, Research Funding; AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding.

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A Phase 1a/b Dose Escalation Study of the MYC Repressor Apto-253 in Patients with Relapsed or Refractory AML or High-Risk MDS

Blood ◽

10.1182/blood-2021-150049 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3411-3411

Author(s):

Maro Ohanian ◽

Martha L. Arellano ◽

Moshe Y. Levy ◽

Kristen O'Dwyer ◽

Hani Babiker ◽

...

Keyword(s):

Clinical Trial ◽

High Risk ◽

Adverse Events ◽

Board Of Directors ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Grade 3 ◽

Refractory Aml

Abstract INTRODUCTION: APTO-253 represses expression of the MYC oncogene by targeting a conserved G-quadruplex structure in its promoter, down-regulates MYC mRNA and protein levels and induces apoptosis in AML cell lines and marrow samples from patients with AML, MDS, and MPN in vitro. After injection, a large fraction of APTO-253 binds iron and transforms to the Fe(253) 3 complex which retains full activity. APTO-253 has been granted orphan drug designation for AML by the US FDA and is being studied in a Phase 1a/b clinical trial in patients with relapsed or refractory AML (R/R AML) or high-risk myelodysplasias (high-risk MDS) (NCT02267863). AIMS: Primary objectives are to determine the safety and tolerability of APTO-253, MTD, dose limiting toxicities (DLT), and the RP2D. Key secondary objectives are to assess the pharmacokinetic (PK) profile, pharmacodynamic (PD) activity, and preliminary evidence of antitumor activity. METHODS: Eligible patients have R/R AML or high-risk MDS for which either standard treatment has failed, is no longer effective, or can no longer be administered safely. Treatment- emergent adverse events (TEAEs) and tumor responses are evaluated using International Working Group criteria. APTO-253 is administered by IV infusion once weekly on days 1, 8, 15, and 22 of each 28-day cycle; ascending dose cohorts were enrolled at a starting dose of 20 mg/m 2 with planned escalation to 403 mg/m 2. RESULTS: As of June 7, 2021, a total of 18 patients (median age 64.0 years, 16 AML and 2 high-risk MDS) with a median of 2.5 prior treatments (range of 1 - 9) have been treated with APTO-253 at doses of 20 (n=1), 40 (n=1), 66 (n=4), 100 (n=4) and 150 mg/m 2 (n=8). Most patients were RBC (87.5% of AML and 100% of MDS) and/or platelet (75% of AML and 50% MDS) transfusion-dependent. No DLTs or drug-related serious adverse events have been reported. Only 1 patient had a drug-related TEAE of grade 3 or greater (fatigue, Grade 3, probably related). Preliminary PK analysis (Figure 1) showed that serum levels of APTO-253 were dose proportional. C max and AUC 0-72h for C1D1 dosing were 0.06, 0.02, 0.36 ± 0.37, 0.44 ± 0.41 and 0.72 ± 0.70 µM and 0.11, 0.15, 3.98 ± 1.77, 4.79 ± 0.87 and 2.51 ± 1.73 µM*h for dose levels of 20, 40, 66, 100 and 150 mg/m 2, respectively. Plasma levels for Fe(253) 3 were significantly higher than those for the APTO-253 monomer. For example, C max and AUC 0-72h of Fe(253) 3 for C1D1 dosing of patients in Cohort 150 mg/m 2 were 2- and 20- fold higher than the ATPO-253 monomer at 15.09 ± 0.42 µM and 51.52 ± 28.26 µM*h, respectively. Following dosing at 150 mg/m 2, serum concentrations of Fe(253) 3 were above 0.5 µM for > 48 h, which approaches the therapeutic range based on in vitro studies. CONCLUSIONS: APTO-253 has been well-tolerated at doses of 20, 40, 66, 100 and 150 mg/m 2 over multiple cycles and escalated to 210 mg/m 2 (Cohort 6). PK analysis revealed that APTO-253 is rapidly transformed to and co-exists with the Fe(253) 3 in serum from R/R AML and high-risk MDS patients. Enrollment of patients at the 210 mg/m 2 dose level is ongoing and updated clinical data will be presented at the meeting. Figure 1 Figure 1. Disclosures Arellano: KITE Pharma, Inc: Consultancy; Syndax Pharmaceuticals, Inc: Consultancy. Levy: AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Other: Promotional speaker; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Epizyme: Consultancy, Other: Promotional speaker; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Dova: Consultancy, Other: Promotional speaker; Novartis: Consultancy, Other: Promotional speaker; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau. Mahadevan: caris: Speakers Bureau; Guardanthealt: Speakers Bureau; PFIZER: Other: Clinical trial Adverse events committee; TG Therapeuticals: Other: Clinical trial Adverse events committee. Zhang: Aptose Biosciences, Inc.: Current Employment. Rastgoo: Aptose Biosciences, Inc.: Current Employment. Jin: Aptose Biosciences, Inc.: Current Employment. Marango: Aptose Biosciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Howell: Aptose Biosciences, Inc.: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Research Funding. Rice: Aptose Biosciences, Inc.: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties; Oncolytics Biotech Inc.: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Bejar: Aptose Biosciences, Inc.: Current Employment, Current equity holder in publicly-traded company; Takeda: Research Funding; BMS: Consultancy, Research Funding; Gilead: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Astex: Consultancy; Silence Therapeutics: Consultancy.

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A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients with Polycythemia Vera

Blood ◽

10.1182/blood-2021-149219 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1504-1504

Author(s):

Srdan Verstovsek ◽

Andrew T. Kuykendall ◽

Ronald Hoffman ◽

Yelena Ginzburg ◽

Naveen Pemmaraju ◽

...

Keyword(s):

Iron Deficiency ◽

Polycythemia Vera ◽

Board Of Directors ◽

Research Funding ◽

Data Safety Monitoring Board ◽

Publicly Traded ◽

Phase 3 ◽

Eligibility Criteria ◽

Advisory Committees ◽

To Receive

Abstract Background. Polycythemia vera (PV) patients are treated with periodic therapeutic phlebotomy (TP) alone or in combination with either hydroxyurea (HU), ruxolitinib (RUX) or interferon (IFN) to maintain hematocrit (HCT) levels below 45% as per NCCN guidelines. Since patients are seen periodically, PV patients may spend significant time with HCT levels above 45%, thereby increasing their risk of thrombosis [Marchioli NEJM 2013]. PV is associated with systemic symptoms with fatigue. These fatigue-related symptoms are found to be the most prevalent and severe as reported in an international survey among PV patients [Scherber Cancer 2016]. Symptomatic iron deficiency represents an unaddressed clinical challenge to PV patients as most PV patients have iron deficiency at diagnosis due to increased iron utilization [Ginzburg Leukemia 2018]. The iron deficiency worsens after repeated TP. We have demonstrated in a phase 2 study that rusfertide (PTG-300) has a good tolerability profile and achieves HCT control in PV patients with improvement in iron deficiency. Methods. This is a Phase 3, multicenter, global, randomized trial that compares the efficacy and safety of rusfertide compared to placebo when added on to current therapy for PV (Figure 1). The study population is PV subjects who require frequent phlebotomies to control their hematocrit with or without concurrent therapy. This is a three-part study in subjects with polycythemia vera: - Part 1a: randomized, double-blind, placebo-controlled, add-on parallel-group period for 32 weeks. Subjects will be stratified by their ongoing PV treatment and randomized 1:1 to rusfertide or placebo added-on to their ongoing PV treatment. - Part 1b: open-label treatment phase during which all subjects who complete Part 1a successfully will receive rusfertide for 20 weeks (Week 32 through Week 52). - Part 2: Long term extension (LTE) phase during which all subjects who complete Part 1b will continue to receive rusfertide for 32 weeks (Week 52 to Week 84). Inclusion Criteria: Approximately 250 subjects will be randomized. Eligibility criteria include PV diagnosis (by 2016 WHO criteria) and frequent phlebotomies with or without concurrent cytoreductive therapy to maintain HCT below 45% in the 6 months prior to enrollment in Part 1. Eligible subjects will continue to receive their therapy at screening for PV (phlebotomy alone (TP) or cytoreductive therapy + TP) and must have a hematocrit <45% at Week 0 prior to randomization. Subjects who meet the eligibility criteria will be stratified by ongoing PV therapy (TP only, TP+hydroxyurea, TP+ruxolitinib, TP+interferon, TP+other) and randomized 1:1 to treatment with rusfertide or placebo added on to the subject's ongoing PV therapy at Week 0. The "add on" design allows subjects to receive standard cytoreductive therapy to control WBC and/or platelets and to receive rusfertide/placebo. The dose of cytoreductive therapy in Part 1a and Part 1b may be decreased for safety but may not be increased for efficacy including control of hematocrit, elevated platelets and/or WBC. Primary endpoint: Proportion of subjects achieving a response starting at Week 20 through Week 32 (inclusive) who receive rusfertide compared to placebo. A response is defined as absence of phlebotomy eligibility defined as either: 1. a confirmed hematocrit ≥45% and that is at least 3% higher than the baseline hematocrit (value immediately prior to randomization at Week 0); confirmation required within 1 to 7 days, or 2. a hematocrit ≥48%. Key words: Hepcidin, Hematocrit, Rusfertide, PTG-300, Polycythemia Vera, PV, Therapeutic Phlebotomy Figure 1 Figure 1. Disclosures Verstovsek: Incyte Corporation: Consultancy, Research Funding; Gilead: Research Funding; PharmaEssentia: Research Funding; Protagonist Therapeutics: Research Funding; CTI BioPharma: Research Funding; Ital Pharma: Research Funding; NS Pharma: Research Funding; Roche: Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; Celgene: Consultancy, Research Funding; Promedior: Research Funding; AstraZeneca: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. Kuykendall: Pharmaessentia: Honoraria; Protagonist: Consultancy, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene/BMS: Honoraria; Abbvie: Honoraria; Incyte: Consultancy; Blueprint: Honoraria. Hoffman: AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding; Novartis: Other: Data Safety Monitoring Board, Research Funding; Protagonist Therapeutics, Inc.: Consultancy; Kartos Therapeutics, Inc.: Research Funding. Pemmaraju: Incyte: Consultancy; HemOnc Times/Oncology Times: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Consultancy, Other: Research Support, Research Funding; Abbvie Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; MustangBio: Consultancy, Other; Stemline Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Celgene Corporation: Consultancy; DAVA Oncology: Consultancy; Dan's House of Hope: Membership on an entity's Board of Directors or advisory committees; Protagonist Therapeutics, Inc.: Consultancy; Roche Diagnostics: Consultancy; LFB Biotechnologies: Consultancy; ASCO Leukemia Advisory Panel: Membership on an entity's Board of Directors or advisory committees; Plexxicon: Other, Research Funding; Samus: Other, Research Funding; Sager Strong Foundation: Other; Aptitude Health: Consultancy; Affymetrix: Consultancy, Research Funding; CareDx, Inc.: Consultancy; Springer Science + Business Media: Other; ASH Communications Committee: Membership on an entity's Board of Directors or advisory committees; Cellectis S.A. ADR: Other, Research Funding; Daiichi Sankyo, Inc.: Other, Research Funding; Clearview Healthcare Partners: Consultancy; Blueprint Medicines: Consultancy; Bristol-Myers Squibb Co.: Consultancy; ImmunoGen, Inc: Consultancy; Pacylex Pharmaceuticals: Consultancy. Valone: Protagonist Therapeutics: Consultancy, Current equity holder in publicly-traded company. Modi: Protagonist Therapeutics: Current Employment. Khanna: Protagonist: Current Employment, Current equity holder in publicly-traded company. O'Connor: Protagonist Therapeutics: Current Employment. Gupta: Protagonist Therapeutics: Current Employment. Kiladjian: Taiho Oncology, Inc.: Research Funding; Novartis: 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; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Other: Personal fees; AOP Orphan: 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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Lenalidomide in High-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia with Chromosome 5 Abnormalities.

Blood ◽

10.1182/blood.v114.22.115.115 ◽

2009 ◽

Vol 114 (22) ◽

pp. 115-115 ◽

Cited By ~ 1

Author(s):

Lars Möllgård ◽

Lars Nilsson ◽

Lars Kjeldsen ◽

Ingunn Dybedal ◽

Inge Hogh Dufva ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Adverse Events ◽

Research Funding ◽

Cytogenetic Response ◽

Underlying Disease ◽

Low Risk ◽

Induction Treatment ◽

Complex Karyotype ◽

A Minor

Abstract Abstract 115 Background: Treatment with lenalidomide in patients with low risk MDS with deletion del(5q) has resulted in a high proportion of transfusion independence and also cytogenetic responses. The aim of this study was to evaluate the effect of lenalidomide in high risk MDS and AML patients with del(5q) or monosomy 5 not eligible for induction treatment, primary cases as well as patients relapsing/refractory to intensive treatment. Methods: This investigator-initiated prospective phase II study assessed the effects of continuous lenalidomide treatment during 16 weeks, in increasing doses from 10 to 30 mg, with 8 weeks on the highest level. Dose modifications due to hematologic toxicity were performed according to the clinical judgment of the treating physician. The primary objective was cytogenetic response, assessed by FISH on bone marrow (BM) smears at inclusion and after 8 and 16 weeks. Clinical and morphological BM response was evaluated every 4 weeks. Results: 25 patients were included from October 2007 to July 2009, 22 of which are so far evaluable. Overall, the patient cohort included several patients with very advanced disease and two patients died before treatment was started. Fourteen MDS patients and 11 AML patients have been included. Twenty-two of the patients had 5q- (9 of these had a complex karyotype and 5 had del(5q)+1) and 3 patients had monosomy 5 (all complex karyotype). The median time of treatment was 13 weeks (range 0–16 weeks). The reason for early termination in the patients who started lenalidomide treatment was progressive disease (3) and adverse events (10). Six of 7 patients who completed the study (16 weeks of treatment) had a response: Two MDS patients with del(5q-)+1, and del(5q)+2, respectively, achieved a major cytogenetic response (≥50 % reduction), in one of these patients the blast count decreased from 9.5% to <5%. Two MDS patients with 5q- and complex karyotype had a minor cytogenetic response (≥25% reduction) and a reduction to <5% blasts, respectively. One AML with 5q- and a complex karyotype had a minor cytogenetic response and a complete BM response. Another AML patient with isolated 5q- showed a complete BM, but no cytogenetic response. In total, 6 of the 20 patients (30%) who started treatment had a cytogenetic and/or morphological BM response. Four of 6 responders also experienced hematologic response. Twenty-one serious adverse events (SAE) have been reported in 15 of the patients. The main SAE criterion has been inpatient hospitalization. Fourteen of the SAE:s were infection or febrile neutropenia. In 6 patients the outcome of the SAE has been death. For these patients the causality/relationship to lenalidomide has been judged as not suspected or not related. The cause of death has been the underlying disease or complications to the underlying disease like infections. Conclusion: Lenalidomide as a single agent, but in higher doses than those applied to low-risk MDS patients resulted in cytogenetic and/or morphological bone marrow response in 30% of patients with high-risk MDS or AML with del(5q) or monosomy 5. We considered this a promising response rate, considering the high frequency of very advanced patients, and complex karyotypes. The main serious adverse event was infections. Future combinations with cytostatic or hypometylating agents may further improve these results. Disclosures: Möllgård: Celgene: Research Funding. Hellström-Lindberg:Celgene: Research Funding.

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A Randomized Phase 2 Study Comparing Acalabrutinib with or without Obinutuzumab in the Treatment of Early Stage High Risk Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Blood ◽

10.1182/blood-2019-123824 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4306-4306 ◽

Cited By ~ 2

Author(s):

Sameer A. Parikh ◽

Eli Muchtar ◽

Betsy Laplant ◽

Wei Ding ◽

Sikander Ailawadhi ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Research Funding ◽

Early Stage ◽

Safety Monitoring ◽

Data Safety Monitoring Board ◽

Phase 2 ◽

Free Survival ◽

Phase 2 Study ◽

Very High

Background: The 2018 iwCLL guidelines recommend close observation of early stage CLL pts who do not meet indications for therapy ("watch and wait" strategy). Prior attempts at early therapeutic intervention in unselected early-stage CLL pts using alkylating agents such as chlorambucil and chemoimmunotherapy failed to show a significant benefit; and these therapies were associated with substantial toxicities. The introduction of Bruton tyrosine kinase (BTK) inhibitors has revolutionized the treatment landscape of CLL. The German CLL Study group recently presented results of the CLL12 study which demonstrated a significant improvement in event-free survival (EFS) among untreated early stage high risk CLL pts who received ibrutinib compared to placebo (median EFS not reached vs. 47.8 months, respectively; Langerbeins, EHA, 2019). Acalabrutinib is a more selective second-generation BTK inhibitor that has fewer adverse events in pts with CLL, and has shown equally impressive clinical activity for CLL pts. We are conducting an investigator initiated randomized phase 2 study to compare acalabrutinib with or without obinutuzumab (a glycoengineered anti-CD20 monoclonal antibody approved in the treatment of CLL) among high risk early stage CLL pts. Study Design: All pts with newly diagnosed (<2 years from registration) previously untreated early stage CLL who do not meet the 2018 iwCLL guidelines for initiation of therapy are eligible for enrollment in this study. Pts undergo risk stratification according to the CLL-International prognostic index (CLL-IPI) which consists of the following 5 variables: age >65 years (1 point), Rai stage I-IV (1 point), del17p and/or TP53 mutation (4 points), unmutated immunoglobulin heavy chain (IGHV) genes (2 points), and serum β2-microglobulin >3.5 g/dL (2 points). Pts with high (4-6) and very high (7-10) risk CLL-IPI are randomly (1:1) assigned to acalabrutinib 100 mg orally twice daily (Arm A) or acalabrutinib with obinutuzumab at a standard approved schedule (Arm B). Treatment with acalabrutinib is continued for a minimum of 2 years unless the patient has unacceptable side effects or withdraws consent. Pts with low (0-1) and intermediate (2-3) risk CLL-IPI score are assigned to an observation arm with follow-up once every 6 months for 2 years, and then according to routine clinical practice (Arm C). Endpoints: The primary endpoint of the intervention arms (Arms A and B) is the achievement of minimal residual disease (MRD)-negative complete remission in the bone marrow after 2 years of therapy. MRD is assessed using an 8-color flow cytometry with a detection limit of 0.01%. The primary endpoint of the observation arm (Arm C) is time to first therapy. Secondary endpoints for all arms are: progression-free survival, overall survival, and safety. Statistical design: A randomized trial comparing the experimental arm (acalabrutinib plus obinutuzumab) against the control arm (acalabrutinib alone) will be conducted as described by Rubinstein. A sample size of 36 pts per arm provides 80% power to detect an improvement in MRD-negative complete response rate from 10% to 30%, using a one-sided test at a significance level of 0.10 (EAST 6.4). We anticipate accruing an additional 8 high/very high risk pts (4 in each arm) to account for ineligibility, cancellation, or major treatment violation. The total enrollment for Arms A and B will be 80 pts. We will enroll 40 pts to Arm C; for a total enrollment of 120 pts. Key correlatives: Comprehensive profiling to assess the innate and adaptive immune system in paired peripheral blood and bone marrow will be conducted in all pts registered to Arms A and B at baseline, 12 and 24 months after enrollment. In addition, bone marrow hematopoietic function will be assessed in all pts at these time points. We will employ a CLL focused custom 61-gene panel to estimate tumor mutational burden as well as mutational profiles for each patient at baseline, 12, and 24 month time points, as well at the time of disease progression. Preliminary results: The trial is registered at clinicaltrials.gov NCT03516617. The trial opened to accrual at all three Mayo Clinic sites (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ) in September 2018. Twenty-eight pts have been registered; the baseline characteristics are shown in Table 1. The trial is expected to complete enrollment in September 2020; and the primary analysis will be available in September 2022. Disclosures Parikh: Janssen: Research Funding; AstraZeneca: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; MorphoSys: Research Funding; AbbVie: Honoraria, Research Funding; Acerta Pharma: Research Funding; Ascentage Pharma: Research Funding; Genentech: Honoraria. Ding:DTRM Biopharma: Research Funding; Merck: Research Funding. Ailawadhi:Pharmacyclics: Research Funding; Cellectar: Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Kenderian:Novartis: Patents & Royalties, Research Funding; Tolero: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Lentigen: Research Funding; Morphosys: Research Funding; Kite/Gilead: Research Funding. Chanan-Khan:Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding; Jansen: Research Funding; AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding. Kay:Infinity Pharmaceuticals: Other: DSMB; Celgene: Other: Data Safety Monitoring Board; Agios: Other: DSMB; MorphoSys: Other: Data Safety Monitoring Board. OffLabel Disclosure: Drug: Acalabrutinib Purpose: treatment of CLL

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REVEAL: Characteristics of Patients with Polycythemia Vera Who Were Diagnosed within 6 Months of Enrollment

Blood ◽

10.1182/blood-2019-121386 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5370-5370

Author(s):

Aaron T. Gerds ◽

Ivy Altomare ◽

Philomena Colucci ◽

Dilan Paranagama ◽

John M Burke

Keyword(s):

High Risk ◽

Polycythemia Vera ◽

Research Funding ◽

Clinical Characteristics ◽

Prospective Observational Study ◽

Low Risk ◽

Early Satiety ◽

High Risk Disease ◽

History Of ◽

Equity Ownership

Background Polycythemia vera (PV), characterized by erythrocytosis and JAK2 mutations, is associated with increased morbidity and mortality. Patients (pts) are at risk for thrombotic events and experience symptoms (sxs) that may impact quality of life. Data describing the clinical characteristics of pts with PV at the time of diagnosis (dx) are limited. The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL) is a multicenter, prospective, observational study designed to collect data on disease burden, clinical management, and pt-reported outcomes (PROs) of adult pts (aged ≥18) with PV. This analysis describes pt demographic and clinical characteristics, treatment patterns, and sxs of newly dxed pts with PV. Methods Pts enrolled in REVEAL who were dxed ≤6 months prior to enrollment were included in this analysis. Descriptive statistics were used to summarize pt demographic and clinical characteristics, tests at dx, and management patterns at dx. Sxs were assessed with a validated PRO instrument: the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Mean and standard deviation for individual sx scores and total sx score (TSS) at enrollment are reported. Results Of the 2510 pts enrolled in REVEAL, 321 dxed within 6 months of enrollment were included in this analysis. Median age at enrollment was 67.0 (range, 23.0-94.0) years, 54.8% were male, and most (74.5%) had high-risk disease (aged ≥60 years and/or history of thrombosis). The most common physician-reported symptoms at the time of presentation included fatigue (24.6%), pruritus (17.1%), insomnia (10.3%), and muscle aches/bone pain (9.7%). Of those pts reported to have undergone mutation testing at dx (n=201), 99.5% were JAK2V617F positive. A history of thrombosis was reported for 15.9% of pts (arterial, 8.1%; venous, 8.7%), and the most common relevant comorbidities were hypertension (58.6%), obesity (19.6%), and diabetes mellitus (15.9%). Of 188 pts with lab values within 1 month before dx, 95.2% had elevated (≥45%) hematocrit and 59.6% had elevated (>10 × 109/L) white blood cell counts. Most high-risk and low-risk pts were reported to have received phlebotomies within 6 months after dx (71.7% and 78.4%, respectively). A higher proportion of pts with high-risk disease initiated a pharmacologic therapy for PV compared with those who had low-risk disease (60.5% vs 23.9%); hydroxyurea (HU) was the most common cytoreductive therapy (n=151 [93.2%]). Most of these pts (n=137 [90.7%]) were still receiving HU 2 years after dx. Of those who initiated HU within 6 months of dx, 5.3% (n=8) received an alternative cytoreductive therapy following HU. A total of 287 pts provided PRO data at enrollment (Table 1). The most common pt-reported sxs were fatigue (77.2%), early satiety (61.1%), and inactivity (58.0%); the mean (SD) MPN-SAF TSS was 18.5 (15.6). The sxs with the highest reported mean (SD) scores were fatigue (3.4 [2.7]), inactivity (2.6 [2.9]), and early satiety (2.5 [2.6]) and were largely similar between low-risk and high-risk pts. Conclusions Compared with all 2510 pts enrolled in REVEAL (Clin Lymphoma Myeloma Leuk 2018[18]12:788-95), this subgroup of 321 pts dxed within 6 months of enrollment was similar with respect to age and sex. However, in the newly dxed subgroup, a slightly lower proportion of pts (74.5%) had high-risk disease (77.3% of the full cohort). In the newly dxed subgroup, a higher proportion of pts (62.6%) underwent mutation testing (49.2% of all enrolled pts). The HU discontinuation rate early in the treatment course was approximately 9.3%, which is similar to the rate (6.3%) of HU discontinuation due to toxicity in patients with PV in a large, multicenter, MPN cohort (Am JHematol 2012[87]5:552-4). Sx burden in pts who completed the MPN-SAF TSS at enrollment was similar in the newly dxed pts (mean TSS, 18.5) and all pts enrolled in REVEAL (18.8; Clin Lymphoma Myeloma Leuk 2018[18]9:590-6); the most frequent pt-reported sxs (fatigue, early satiety, and inactivity) in this smaller pt subgroup were the same as those observed in the larger pt cohort. Overall, near the time of dx, a greater proportion of pts had low-risk disease. Despite this difference, the sx constellation and severity tends to be very similar to the larger cohort. It also appears that only a very small proportion of pts are unable to tolerate HU early on in the course of the disease. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Celgene Corporation: Consultancy, Research Funding; Roche: Research Funding. Altomare:Novartis: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; Rigel: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Burke:Roche/Genentech: Consultancy; Celgene: Consultancy; Gilead: Consultancy.

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Clinical Characteristics and Treatment Patterns By Risk Stratification in Patients with Essential Thrombocythemia: An Analysis of the MOST Study

Blood ◽

10.1182/blood-2020-134841 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 12-13

Author(s):

Michael R. Grunwald ◽

Ivy Altomare ◽

Robyn M. Scherber ◽

Patricia Kalafut ◽

Haobo Ren ◽

...

Keyword(s):

High Risk ◽

Observational Study ◽

Essential Thrombocythemia ◽

Research Funding ◽

Clinical Characteristics ◽

Symptom Burden ◽

Low Risk ◽

Publicly Traded ◽

Real World Data ◽

Patient Reported

Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by thrombocytosis and increased risk of thrombotic events and hemorrhage. Treatment of ET is risk-adapted, focused on preventing thrombosis, bleeding, and minimizing symptoms. Real-world data regarding factors contributing to treatment initiation and therapy choice in this setting are limited. Here, we present the clinical characteristics of low- and high-risk pts with ET enrolled in Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) and assess whether these differ for pts who were treated vs untreated at the time of enrollment. Methods: MOST (NCT02953704) is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in pts with specific risk categories of ET or MF. Pts included in this analysis met modified ELN criteria (J Clin Oncol. 2011;29:761) for high-risk ET (age ≥60 y and/or thromboembolic event [TE] history) or low-risk ET if receiving ET-directed therapy (not including aspirin only). Data from pt records were entered into an electronic case report form during usual-care visits over a planned observation period of 36 months. Patient-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 1235 pts with ET enrolled at 124 sites between 11/29/2016 and 12/31/2018, 1210 were included in the analysis; 25 were excluded (low-risk receiving aspirin alone [n=16]; low risk receiving neither ET-directed therapy nor aspirin [n=8]; BCR-ABL mutation-positive [n=1]). Of the 1210 pts analyzed, 159 (13.1%) were low-risk (all treated), 887 (73.3%) were high-risk and treated, and 164 (13.6%) were high-risk and untreated, respectively. Reasons for high-risk categorization were similar for treated and untreated high-risk pts (age ≥60 y, 67.5% vs 70.1%; TE history, 8.8% vs 10.4%; both age ≥60 y and TE history, 23.7% vs 19.5%). Pt characteristics are listed in Table 1A. Compared with low risk pts, significantly more high risk pts were JAK2 V617F positive (P = 0.0143); fewer were CALR positive, and more were MPL positive. Pts with high-risk disease who were untreated had the highest proportion of palpable splenomegaly; mean palpable spleen length below the costal margin was greater in treated pts (low- and high-risk) than in untreated pts. Blood counts were similar across cohorts, except platelets were elevated for untreated high-risk pts. The proportion of pts with comorbidities was similar across cohorts; cardiovascular comorbidities were not as common among low- vs high-risk pts. Mean TSS was highest for low-risk pts, and was similar in both treated and untreated high-risk pts. Fatigue was the most severe symptom in all cohorts. Mean MPN-SAF TSS was significantly higher for low- vs high risk pts (P = 0.0007), as were several individual symptom scores (abdominal discomfort, P = 0.0081; concentration, P = 0.0014; numbness/tingling, P = 0.0361; night sweats, P < 0.0001; itching, P = 0.0131; bone pain, P = 0.0206; weight loss, P = 0.0469). Physician-reported signs and symptoms were generally more common in low- vs high-risk pts, with differences between risk groups reaching significance for headache (P = 0.0009) and abdominal pain (P = 0.0455). Among currently untreated high-risk pts, 40.9% had not received any previous ET-directed therapy. Hydroxyurea (HU) was the most common ET-directed monotherapy at enrollment in both low- and high-risk treated pts (Table 1B). A small proportion of pts in both low- and high-risk treated groups was receiving >1 ET-directed therapy. Conclusion: These real-world data from the MOST study indicate that despite treatment, low-risk pts had greater patient-reported symptom burden and physician-reported signs/symptoms than high-risk (treated or untreated) pts. This finding suggests that current management (most commonly with HU in this analysis) may not address symptoms in low-risk pts. Notably, nearly 60% of currently untreated high-risk pts had been previously treated, highlighting an unmet need for effective and tolerable second-line treatments in pts with high-risk ET. Further analyses from MOST will help define changes in the clinical and treatment characteristics of pts with ET over time. Disclosures Grunwald: Premier: Consultancy; Janssen: Research Funding; Amgen: Consultancy; Celgene: Consultancy; Merck: Research Funding; Genentech/Roche: Research Funding; Amgen: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Premier: Consultancy; Astellas: Consultancy; Astellas: Consultancy; Premier: Consultancy; Forma Therapeutics: Research Funding; Cardinal Health: Consultancy; Merck: Consultancy; Merck: Consultancy; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Janssen: Research Funding; Abbvie: Consultancy; Incyte: Consultancy, Research Funding; Genentech/Roche: Research Funding; Amgen: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Genentech/Roche: Research Funding; Incyte: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Pfizer: Consultancy; Cardinal Health: Consultancy; Agios: Consultancy; Merck: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Abbvie: Consultancy. Altomare:Bayer: Consultancy; Rigel: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Research Funding; Novartis: Consultancy. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Blueprint Medicines Corp: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; ItalPharma: Research Funding; Gilead: Research Funding; CTI Biopharma Corp: Research Funding; Genentech: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Protagonist Therapeutics: Research Funding; Promedior: Research Funding; Incyte Corporation: Consultancy, Research Funding.

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Prediction of Early Mortality with Non-Intensive Acute Myeloid Leukemia (AML) Therapies: Analysis of 1336 Patients from MRC/NCRI and SWOG

Blood ◽

10.1182/blood-2021-151597 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 220-220

Author(s):

Xu Wang ◽

Ian Thomas ◽

Cono Ariti ◽

Mike Dennis ◽

Priyanka Mehta ◽

...

Keyword(s):

Research Funding ◽

Regression Models ◽

Early Death ◽

Safety Monitoring ◽

Data Safety Monitoring Board ◽

Publicly Traded ◽

Npm1 Mutation ◽

Mutation Status ◽

Logistic Regression Models ◽

Multivariable Models

Abstract Background: Therapeutic resistance and treatment tolerance vary greatly in patients with AML, likely due to the advanced age and genetic diversity in pharmacokinetics of those affected. Undoubtedly, tools to accurately predict outcomes of individual therapies for patients could inform decision-making and improve response rates. To this end, several scoring systems have been developed aimed at identifying patients at high risk of poor outcome after intensive chemotherapy. Similar tools for use after non-intensive therapies are currently not available. As such therapies are increasingly effective and more widely utilized we sought to develop tools to predict early death and survival for patients treated with non-intensive therapies. Patients and Methods: We developed prediction models for all-cause death by day 28, 42, 56, and 100 from enrollment using data from 796 patients enrolled on MRC/NCRI trial LI-1, which we then validated in a cohort of 540 patients treated on SWOG trials S0432, S0703, and S1612. Treatments included: Low dose Ara-C (LDAC) alone, sapacitabine alone and LDAC in combination with vosaroxin, tosedostat or ganetespib (MRC/NCRI); Azacytidine (AZA) alone, tipifarnib alone, and AZA in combination with mylotarg, midostaurin, and nivolumab (SWOG). The following covariates were available in the MRC/NCRI and SWOG cohorts to build multivariable logistic regression models (quantitative unless specified otherwise): age, performance status (PS; 0-1 vs. 2-4), secondary AML (vs. de novo AML or high-risk myelodysplastic syndrome), white blood cell and platelet counts, and percentage of bone marrow blasts - all assessed at enrollment. The regression coefficients from the model fit in the MRC/NCRI cohort were used to derive a score and applied to each patient in the SWOG cohort. The models' prognostic accuracies were assessed using the area under the receiver operating characteristic curve (AUC). For the MRC/NCRI cohort, additional covariates were available: cytogenetic risk (per Grimwade 2011), FLT3-ITD, and NPM1 mutation and patient-reported outcomes using the QLQ-C30 instrument. Logistic regression models with these covariates were fit and optimism-corrected AUC estimated to assess prognostic performance for early death. Results: Both patient cohorts were largely composed of older individuals (median age of 75 [range: 60-91] for MRC/NCRI and 77 [60-94] for SWOG, respectively. A substantial subset in each had a PS of 2-4 (MRC/NCRI: 20%; SWOG: 37%) and/or secondary AML (MRC/NCRI: 26%; SWOG: 41%). Overall, the ability to predict early death either by day 28, 42, 56, or 100 was limited in the MRC/NCRI cohort. Subscales of the QLQ-C30 had univariate AUC=0.67, the highest among all covariates evaluated. Multivariable models with just clinical covariates had optimism-corrected AUCs ranging from 0.63-0.65; adding cytogenetic risk and FLT3-ITD and NPM1 mutation status led optimism-corrected AUCs ranging from 0.64-0.66; addition of two QLQ-C30 subscales (fatigue and appetite loss) led to optimism-corrected AUCs ranging from 0.66-0.69. The SWOG cohort did not collect QLQ-C30 or mutational data on all patients and only the clinical multivariable models could be evaluated. The models had a similar performance in the SWOG cohort with AUCs ranging from 0.65-0.68. Conclusion: Our ability to predict early death in older patients treated with lower intensity AML therapies is limited with routinely available clinical variables. Inclusion of cytogenetic risk, FLT3-ITD, and NPM1 mutation status minimally improved the prognostic accuracy as did some of the QLQ-C30 subscales. Our data highlight the difficulties in predicting outcomes with non-intensive AML therapy with routinely available baseline clinical information. Improving the clinical utility of these models may require more complete characterization of patient comorbidities (including frailty index, cognitive function, renal and hepatic function, comorbidity scores) or additional PRO measures since some QLQ-C30 subscales had the strongest univariate signals. Support: NIH/NCI grants CA180888 and CA180819; Blood Cancer UK grant 13041 and Cardiff University. Figure 1 Figure 1. Disclosures Assouline: Novartis: Honoraria, Research Funding; Amgen: Current equity holder in publicly-traded company, Research Funding; Gilead: Speakers Bureau; Johnson&Johnson: Current equity holder in publicly-traded company; Jewish General Hospital, Montreal, Quebec: Current Employment; Eli Lilly: Research Funding; Roche/Genentech: Research Funding; Takeda: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Erba: AbbVie Inc; Agios Pharmaceuticals Inc; Astellas; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Daiichi Sankyo Inc; Genentech, a member of the Roche Group; GlycoMimetics Inc; Incyte Corporation; Jazz Pharmaceuticals Inc; Kura Oncology; Nov: Other: Advisory Committee; AbbVie Inc: Other: Independent review committee; AbbVie Inc; Agios Pharmaceuticals Inc; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Incyte Corporation; Jazz Pharmaceuticals Inc; Novartis: Speakers Bureau; AbbVie Inc; Agios Pharmaceuticals Inc; ALX Oncology; Amgen Inc; Daiichi Sankyo Inc; FORMA Therapeutics; Forty Seven Inc; Gilead Sciences Inc; GlycoMimetics Inc; ImmunoGen Inc; Jazz Pharmaceuticals Inc; MacroGenics Inc; Novartis; PTC Therapeutics: Research Funding. Walter: Jazz: Research Funding; Pfizer: Consultancy, Research Funding; Selvita: Research Funding; Amphivena: Consultancy, Other: ownership interests; Agios: Consultancy; Astellas: Consultancy; BMS: Consultancy; Genentech: Consultancy; Janssen: Consultancy; Kite: Consultancy; Macrogenics: Consultancy, Research Funding; Immunogen: Research Funding; Celgene: Consultancy, Research Funding; Aptevo: Consultancy, Research Funding; Amgen: Research Funding. Othus: Daiichi Sankyo: Consultancy; Celgene: Other: Data safety monitoring board; Merck: Consultancy; Biosight: Consultancy; Glycomimetics: Other: Data safety monitoring board.

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Modified STOP-Bang for predicting perioperative adverse events in the Thai population

BMC Anesthesiology ◽

10.1186/s12871-021-01347-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lisa Sangkum ◽

Chama Wathanavaha ◽

Visasiri Tantrakul ◽

Munthana Pothong ◽

Cherdkiat Karnjanarachata

Keyword(s):

High Risk ◽

Adverse Events ◽

Oxygen Therapy ◽

Elective Surgery ◽

Low Risk ◽

Perioperative Outcomes ◽

P Value ◽

Icu Admission ◽

Obstructive Sleep ◽

Postanesthetic Care Unit

Abstract Background Undiagnosed obstructive sleep apnea (OSA) is associated with adverse perioperative outcomes. The STOP-Bang questionnaire is a validated screening tool for OSA. However, its precision may vary among different populations. This study determined the association between high-risk OSA based on the modified STOP-Bang questionnaire and perioperative adverse events. Methods This cross-sectional study included patients undergoing elective surgery from December 2018 to February 2019. The modified STOP-Bang questionnaire includes a history of Snoring, daytime Tiredness, Observed apnea, high blood Pressure, Body mass index > 30 kg/m2, Age > 50, Neck circumference > 40 cm, and male Gender. High risk for OSA was considered as a score ≥ 3. Results Overall, 400 patients were included, and 18.3% of patients experienced perioperative adverse events. On the basis of modified STOP-Bang, the incidence of perioperative adverse events was 23.2 and 13.8% in patients with high risk and low risk (P-value 0.016) (Original STOP-Bang: high risk 22.5% vs. low risk 14.7%, P-value 0.043). Neither modified nor original STOP-Bang was associated with perioperative adverse events (adjusted OR 1.91 (95% CI 0.99–3.66), P-value 0.055) vs. 1.69 (95%CI, 0.89–3.21), P-value 0.106). Modified STOP-Bang ≥3 could predict the incidence of difficult ventilation, laryngoscopic view ≥3, need for oxygen therapy during discharge from postanesthetic care unit and ICU admission. Conclusions Neither modified nor original STOP-Bang was significantly associated with perioperative adverse events. However, a modified STOP-Bang ≥3 can help identify patients at risk of difficult airway, need for oxygen therapy, and ICU admission. Trial registrations This study was registered on Thai Clinical Trials Registry, identifier TCTR20181129001, registered 23 November 2018 (Prospectively registered).

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Short-term risk stratification using CADILLAC risk score in patients with ST elevation myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1352 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Satou ◽

H Kitahara ◽

K Ishikawa ◽

T Nakayama ◽

Y Fujimoto ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Adverse Events ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Short Term ◽

Recurrent Myocardial Infarction ◽

St Elevation

Abstract Background The recent reperfusion therapy for ST-elevation myocardial infarction (STEMI) has made the length of hospital stay shorter without adverse events. CADILLAC risk score is reportedly one of the risk scores predicting the long-term prognosis in STEMI patients. Purpose To invenstigate the usefulness of CADILLAC risk score for predicting short-term outcomes in STEMI patients. Methods Consecutive patients admitted to our university hospital and our medical center with STEMI (excluding shock, arrest case) who underwent primary PCI between January 2012 and April 2018 (n=387) were enrolled in this study. The patients were classified into 3 groups according to the CADILLAC risk score: low risk (n=176), intermediate risk (n=87), and high risk (n=124). Data on adverse events within 30 days after hospitalization, including in-hospital death, sustained ventricular arrhythmia, recurrent myocardial infarction, heart failure requiring intravenous treatment, stroke, or clinical hemorrhage, were collected. Results In the low risk group, adverse events within 30 days were significantly less observed, compared to the intermediate and high risk groups (n=13, 7.4% vs. n=13, 14.9% vs. n=58, 46.8%, p<0.001). In particular, all adverse events occurred within 3 days in the low risk group, although adverse events, such as heart failure (n=4), recurrent myocardial infarction (n=1), stroke (n=1), and gastrointestinal bleeding (n=1), were substantially observed after day 4 of hospitalization in the intermediate and high risk groups. Conclusions In STEMI patients with low CADILLAC risk score, better short-term prognosis was observed compared to the intermediate and high risk groups, and all adverse events occurred within 3 days of hospitalization, suggesting that discharge at day 4 might be safe in this study population. CADILLAC risk score may help stratify patient risk for short-term prognosis and adjust management of STEMI patients. Initial event occurrence timing Funding Acknowledgement Type of funding source: None

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Sernbo score predicts survival after intracapsular hip fracture in the elderly

Annals of The Royal College of Surgeons of England ◽

10.1308/003588413x13511609954653 ◽

2013 ◽

Vol 95 (1) ◽

pp. 29-33 ◽

Cited By ~ 20

Author(s):

EJC Dawe ◽

E Lindisfarne ◽

T Singh ◽

I McFadyen ◽

P Stott

Keyword(s):

Hip Fracture ◽

High Risk ◽

Risk Group ◽

Characteristic Curve ◽

Social Situation ◽

High Risk Group ◽

Low Risk ◽

Risk Of Death ◽

Intracapsular Hip Fracture ◽

The Mean

Introduction The Sernbo score uses four factors (age, social situation, mobility and mental state) to divide patients into a high-risk and a low-risk group. This study sought to assess the use of the Sernbo score in predicting mortality after an intracapsular hip fracture. Methods A total of 259 patients with displaced intracapsular hip fractures were included in the study. Data from prospectively generated databases provided 22 descriptive variables for each patient. These included operative management, blood tests and co-mobidities. Multivariate analysis was used to identify significant predictors of mortality. Results The mean patient age was 85 years and the mean follow-up duration was 1.5 years. The one-year survival rate was 92% (±0.03) in the low-risk group and 65% (±0.046) in the high-risk group. Four variables predicted mortality: Sernbo score >15 (p=0.0023), blood creatinine (p=0.0026), ASA (American Society of Anaesthesiologists) grade >3 (p=0.0038) and non-operative treatment (p=0.0377). Receiver operating characteristic curve analysis showed the Sernbo score as the only predictor of 30-day mortality (area under curve 0.71 [0.65–0.76]). The score had a sensitivity of 92% and a specificity of 51% for prediction of death at 30 days. Conclusions The Sernbo score identifies patients at high risk of death in the 30 days following injury. This very simple score could be used to direct extra early multidisciplinary input to high-risk patients on admission with an intracapsular hip fracture.

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