Impact of COVID-19 on the progression of benign prostatic hyperplasia and aggravation of related symptoms: A prospective study.

OBJECTIVE: This study aims to evaluate the lower urinary tract symptoms (LUTS) of the patients with benign prostatic hyperplasia (BPH) who were admitted due to coronavirus disease (COVID-19) and to show the effect of COVID-19 on BPH. METHODS: This prospective study included patients over the age of 45 admitted due to COVID-19 between June 2021 and December 2021 and treated with alpha-blockers for BPH. During admission, the patients were evaluated by prostate volumes, prostate-specific antigen (PSA) values, and International Prostate Symptom Scores (IPSS). Furthermore, treatment duration due to COVID-19, frequency, nocturia, and voided volumes obtained from the voiding diary was recorded. Finally, the sequent IPSS values were compared by inviting the patients to the urology polyclinic in the first month. RESULTS: The mean age of 142 patients was 72.42 ± 10.21 years. The IPSS scores of the patients increased from 10.66 ± 4.46 to 12.99 ± 3.58 1 month after the diagnosis (p < 0.01). Moreover, the IPSS quality of life (QoL) scores were 2.44 ± 0.58 and 2.75 ± 0.51, respectively (p < 0.01). The mean frequency obtained from the voiding diary data increased from 5.10 ± 1.5 to 5.65 ± 1.36 (p < 0.01), mean nocturia count increased from 1.13 ± 0.05 to 1.39 ± 0.66 per day (p < 0.01), and the mean voiding volume decreased from 320.56 ± 46.76 ml to 298.84 ± 39.74 ml (p < 0.01). CONCLUSION: In this study, we detected an increase in LUTS during COVID-19 treatment. Therefore, it should be noted that symptomatic or asymptomatic COVID-19 patients may refer to urology polyclinics due to aggravation of LUTS.

Can we predict HoLEP surgery operating times for a given prostate volume to enhance theatre utilization?

Introduction & Objectives: Holmium laser enucleation of the prostate (HoLEP) has the strongest evidence base for bladder outlet surgery, despite its steep learning curve. Rapid enucleation rates can be achieved in established hands with day-case surgery being the norm in service delivery. We have previously shown the validity of such a model. With the post Covid surgical backlog we have developed a tool to support theatre utilization based on established surgeon specific operating room (OR) times for a given prostate volume in our unit based on almost 1100 cases. Material(s) and Method(s): Four HoLEP naive surgeons completed 1096 HoLEPs over 7.5 years using a 50 Watt (W) Holmium laser (Auriga XL, Boston Scientific Inc., Piranha morcellator, Richard Wolf). Pre and post-operative data including TRUS/MRI volume, flow rate, residual volume, international prostate symptom score, quality of life, stop-clock enucleation, morcellation and total operating room (OR) times, hospital stay, histology, haemoglobin, creatinine, sodium and catheter times were prospectively recorded. Mentorship was provided by a senior 100W HoLEP surgeon from an adjoining hospital. Result(s): The data was independently analysed by a bio-statistician (IN). Statistical regression analysis of unit and surgeon specific OR times vs prostate volume were used to produce predictive linear graphs of OR times (mins) for a given prostate volume for individual surgeons and the unit. [Figure presented] Conclusion(s): Use of surgeon-specific and unit specific OR times allows the opportunity to maximize theatre operating schedules to help tackle the post Covid surgical backlog. We encourage this process for index specialist procedures across units.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Changes in Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia Patients Affected by Covid-19.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a histological diagnosis characterized by an increase in the number of epithelial and stromal cells in the transitional zone of the prostate gland. The clinical manifestation of BPH is associated with the appearance of so-called lower urinary tract symptoms (LUTS) which can also be a consequence of other conditions not related to the prostate. Covid-19, also known as severe acute respiratory syndrome coronavirus 2 was discovered as a disease in late 2019 in the city of Wuhan, China. MATERIALS AND METHODS: A case-control study was conducted between September 2021 and May 2022. Information was initially collected on 60 patients followed up and treated conservatively for BPH in two outpatient practices and recovered from Covid-19. After processing the received information, 27 patients were excluded from the study and 33 patients remained for observation The assessment of patients is carried out through an internationally validated questionnaire - international prostate symptom score (IPPS), prostate specific antigen, digital rectal examination (DRЕ), and ultrasound diagnostics of the prostate gland with consideration of its volume and the amount of residual urine. RESULTS: Our data show a strong correlation between the changes in LUTS in patients with BPH and Covid-19 infection. CONCLUSION: Although almost 3 years have passed since the beginning of this pandemic, there are still many unanswered questions surrounding this disease. We believe that with our experience we will enrich the information about the relationship between Covid-19 and LUTS, and the results obtained by us can serve as a basis for future large-scale and more in-depth studies on the subject.

De Novo or Increasing Lower Urinary Tract Symptoms during COVID-19 Infection: Long-term Results

Background: How COVID-19 affects lower urinary tract symptoms (LUTS) in men has not been demonstrated by published research. This study examined the de novo development of LUTS and the change in the severity of pre-existing LUTS in men hospitalized with COVID-19. A follow-up period of 12 months after COVID-19 infection provided data on the long-term effect of COVID-19 vs. LUTS. Methods: Data were collected from 70 male patients diagnosed with COVID-19 via nasopharyngeal swab RT-PCR technology between June 2020 and April 2021. The patient’s age, comorbidities, date of COVID-19 diagnosis, date of LUTS, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), creatinine, and D-dimer levels, urinalysis, urine culture and duration of hospital stay were recorded. Statistical analyses were conducted to compare between pre-COVID and post-COVID IPSS and other data. Results: 42 patients were included in this study with a, mean age of patients were 54.76 ± 11.95 years. In 8 patients there was no change in IPSS prevs. post-COVID. In the remaining 34 patients (80.9%), the median IPSS increased from a pre-COVID value of 2 to 10 during COVID (p < 0.001). In the subgroup analysis based on age <50 years vs. ≥50 years, statistically significant increase in IPSS were found in both age groups pre- and post-COVID. Conclusions: In male patients of all ages, COVID-19 results in the de novo occurrence of LUTS and an increase in pre-existing LUTS in approximately 80% of patients. These symptoms were found to persist at a 12-months follow-up.

Safety and efficacy of REZUM for the treatment of BPH in an Australian cohort

Introduction & Objectives: Minimally invasive transurethral therapies for benign prostatic hypertension are becoming increasingly common in Europe and America. They may be performed under local anaesthetic and provide a good alternative to invasive procedures in a COVID era. REZUM, a minimally invasive transurethral water-vapor therapy, has been shown to be a safe and effective treatment for BPH, especially where preserved sexual function is a priority. Although short-term clinical outcomes are promising, long-term data from robust studies is lacking. In Australia, there are few providers of REZUM, which utilises steam injections to reduce prostatic tissue. This study aims to investigate the safety and efficacy of REZUM in an Australian cohort. Methods: A clinical audit was conducted of 50 patients who underwent REZUM to treat symptoms of BPH over a 12-month period. Procedures were performed under general anaesthetic. Demographics, comorbidities, sexual function, prostate volume, PSA, voiding flow rate, post-void residual volume and International Prostate Symptom Score were extracted from medical records, in addition to patient's reasons for seeking minimally invasive treatment. Corresponding post-operative data was collected. Descriptive statistics of the cohort were obtained using Stata 16.0. Paired t-test was used to identify if there was a significant difference between IPSS scores pre- and postprocedure Results: Patients accessing treatment ranged from 48 to 84 years (mean 64.6). Median prostate volume was 55mL (inter-quartile range 45-78mls) and mean International Prostate Symptom Score (IPSS) was 20.3. 28% of the cohort cited concern for ejaculatory function, either from medication side effects or TURP, as their primary reason for seeking minimally invasive treatment. A further 25% of the cohort was additionally concerned about other side effects from medications and/or TURP or had experienced medication failure. The mean follow up period was 6 months (range 6-weeks-26 months). 69% of men were satisfied with their symptom improvement at the time of review, with the expectation of ongoing improvement in men who had attended a 6-week post-operative review only. Postprocedure mean IPSS was 7.9 (range 2-33). Mean reduction in IPSS score post-procedure was 12.7 points (p<0.001). 3 men experienced complications (retention, infection, bulbar stricture). Conclusions: REZUM provides a safe alternative to traditional invasive prostatic treatments. It may be performed under local anaesthetic, providing an effective alternative in a COVID era. Men concerned about medications, more invasive treatments and ejaculatory dysfunction are increasingly seeking relief from this minimally invasive option and experiencing good outcomes including significant symptom improvement sustained over medium-term follow up.

LONG TERM FOLLOW-UP OF AN INTERNATIONAL MULTICENTER PROSPECTIVE STUDY IN APPLICATION OF TEMPORARY IMPLANTABLE NITINOL DEVICE (ITIND) IN MEN WITH LOWER URINARY TRACT SYMPTOMS FOR BPH

INTRODUCTION AND OBJECTIVE: To report IPSS, QoL and treatment failure rate up to 79-months for the MT02 study with implantation of the temporary implantable nitinol device (iTind;Medi- Tate Ltd®, Israel) in men with lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO). METHODS: Three out of nine international centers consented to continue the international prospective multicenter study on patients with LUTS due to BPO (IPSS ≥10, Qmax <12ml/sec, and prostate volume <75ml) beyond 36 months following implantation of iTind. Out of the originally enrolled 81 patients, 50 were followed-up at sites in Italy, Switzerland, and Belgium. Due to Covid-19 the originally planned follow-up scheme was amended: Each patient was assessed once during a timeframe of 50-79 months post-operatively by IPSS and IPSS-QoL, change in medication and adverse events via a telephone call. Patients were analyzed in three groups according to their follow-up time point (clustered into groups from 48-59 months, 60-71 months, and 72-83 months). RESULTS: Fifty to 79 months results were available for 42 patients. Four patients were lost to follow-up and two patients deceased from reasons unrelated to the iTind device. Only two patients had treatment failures (one patient underwent TURP, the other ThuLEP), while no patient required any additional medication. IPSS average results were 12.63±8.84 (50-59m, N=24), 8.85±5.54 (60-71m, N =13) and 9.20 ±5.85 (72-79m, N=5). QoL average results were 2.21±1.69 (50-59m, N=24), 1.85±0.99 (60-71m, N=13) and 1.80±1.10 (72-79m, N=5). IPSS (-8.88, -10.31, and -9.60) and IPSSQoL (-2.04, -1.85 and -1.80) improved significantly for all groups vs. baseline, respectively (p <0.0001). Functional data is shown in Figure 1. No late post-operative complications were observed between 50 and 79 months. CONCLUSIONS: iTind for treatment of LUTS secondary to BPO is an effective and safe procedure providing significant and effective reduction in symptoms and quality of life durable up to 79 months (6.6 years) with only 4% of treatment failures after 3-year follow-up. (Figure Presented).

OFFICE BASED TRANSPERINEAL LASER ABLATION FOR BENIGN PROSTATIC HYPERPLASIA: 3 & 6 MONTHS OUTCOMES

INTRODUCTION AND OBJECTIVE: BPH affects tens of millions of men across the world. Most procedures require either general or regional anesthesia or a transurethral approach. Herein, we present the 3 & 6 months results of NCT04760483 is a phase I prospective, single center, interventional pilot study evaluating transperineal laser ablation (TPLA) of BPH tissues, carried in Office setting under local anesthesia. A detailed step by step video depiction of this procedure is available at the AUA video library. The objectives call for safety, feasibility, and impact in pertinent outcomes measures, such as Uroflowmetry, IPSS, Hematuria, Erectile function, and ejaculation METHODS: The study contemplated accrual of 20 men between 50 and 80 years with prostate volumes between 30 and 120 cc, IPSS scores >9, peak flows between 5 and 15 cc/s and void residuals under <250 ml. Any patient neurological conditions, history of any surgical intervention or urinary retention were excluded. IPSS assessments, Flow studies and prostate volume measures were conducted at 3 months. Herein we present the results. Bayesian analysis for continuous measurements were performed and non-parametric differences were evaluated using chi2 tests. RESULTS: Patients enrolled between December 2020 and February of 2021. The median (IQR) for age and BMI was 68 (58,73) and 29 (27,31), respectively. These parameters for room time, ablation time, watts and total joules were 29 (23,32), 9 minutes (7,12), 6 (5,7) watts and 3,400 (2,600, 3600) joules, respectively. 8(40%) were discharged with a Foley due to elevated residuals. 16 patients had erections and ejaculations before and 3 months after TPLA. 17/20 (85%) had significant improvement in their urinary profile after TPLA (See TABLE for details). One of the initial responders suffered from COVID- 19 infection and developed a CVA that hindered his urinary function. CONCLUSIONS: TPLA in the office setting is feasible and safe. Three month outcomes showed subjective and objective sustained improvement in over 80% of patients for at least 6 months. Furthermore, erections or ejaculations were not affected. This novel and promising approach demands further evaluation in phase II-III trials. (Figure Presented).

Pelvic Floor HIFEM in Men Improves Ejaculation

Introduction: High-Intensity Focused Electromagnetic (HIFEM) field technology utilizes rapidly changing magnetic fields that generate electrical currents in the underlying tissue where it depolarizes motor neurons and causes muscle contractions. BTL Emsella provides non-invasive electromagnetic stimulation of pelvic floor musculature for the purpose of rehabilitation of weak pelvic muscles and restoration of neuromuscular control for the treatment of male and female incontinence. Novel protocol U2 is intended for men and uses a field intensity max of 2.5 T and a 10 cm depth of penetration for 28 minutes. Objective: Determine the effects of High-Intensity Focused Electromagnetic (HIFEM) field technology on the intensity and duration of ejaculation in men, with additional observations on erectile function using the IIEF-15 and urination using the IPSS. Methods: We looked at the effects of HIFEM on ejaculation, erectile function, and urination. Our IRB-approved protocol was one 28 minutes pelvic floor treatment per week for 4 weeks. At baseline, end of treatment, and one month post-treatment, the patient completed the IIEF-15, IPSS, and the LuBE Score, a four-question 5 point Likert style questionnaire created specifically for this study to investigate patient-reported aspects of orgasm, including volume, force, duration, and intensity of ejaculation. 0 is no change, 1 is increased, 2 is dramatically increased, -1 is decreased, -2 is dramatically decreased. Men participated with their sexual partners who also received four weekly treatments. Results: 12 men, average age of 57, completed the protocol. The range of the LuBE score is -8 to 8. The LuBE Score increased from baseline 0 up to 2.1 (median is 3 with a range of -1 to 5) to 2.7 (median of 3 with a range of 0 to 4) one month after the completion of treatment. The IIEF-15 increased from 54 at baseline to 60.3 at the completion of treatment and 60.4 one month after the completion of treatment. The IPSS declined from 7.1 to 4.6 at the completion of treatment and down to 3.3 one month after th Conclusions: We conclude that the U2 protocol for HIFEM boosts the strength of the bulbocavernosus and ischiocavernosus muscle and the pelvic floor resulting in an increase in volume, force, duration and intensity of ejaculation. In addition, there was a six-point increase in IIEF-15 score. There was a 3 to 4 point drop in IPSS score. We were surprised to see improvements in IIEF-15 and IPSS, and this should be investigated further. COVID limited patient recruitment, but the results indicate that pelvic HIFEM potentially improves ejaculation. Based on patient communications, I believe that more treatments than the four provided will add to the benefits. I plan on studies with more participants and extended treatment sessions. Disclosure: Yes, this is sponsored by industry/sponsor: BTL Clarification: No industry support in study design or execution Any of the authors act as a consultant, employee or shareholder of an industry for: AFFIRM Science

Efficacy of Oral Decitabine/Cedazuridine (ASTX727) in the CMML Subgroup from the Ascertain Phase 3 Study

text: Background/Introduction: Chronic Myelomonocytic Leukemia (CMML) is an uncommon MDS/MPN overlap syndrome that has historically been included under the umbrella of myelodysplastic syndromes (MDS) for clinical trial and treatment. As a result, DNA methyltransferase inhibitors (DNMTi) such as decitabine or azacitidine have been the established standard of care for the treatment of CMML. The oral bioavailability of these agents has been limited due to rapid degradation by cytidine deaminase (CDA) in the gut and liver so treatment has required intravenous infusion or subcutaneous injections daily for 5-7 days every month (m) adding significant burden to older cancer patients due to daily time commitment and travel to treatment centers. In the context of pandemic SARS-CoV-2, parenteral therapy also increases contact with medical settings with increased infection risk. Oral decitabine 35 mg/cedazuridine 100 mg (ASTX727) is an oral fixed dose combination of decitabine and the CDA inhibitor cedazuridine that produced equivalent exposure (99%;90% CI 93% to 106%) to IV decitabine 20 mg/m 2 in a randomized cross-over study (Garcia-Manero et al, ASH 2019), and Median overall survival (mOS) for the entire study population in the ASCERTAIN study was approximately 32 months (Savona, 2021). Here, we present outcome data for this study for the enrolled subpopulation of patients with CMML. Methods: We used a randomized cross over design in which patients were randomized in the first 2 cycles 1:1 to either Sequence A: (decitabine 35 mg/ cedazuridine 100 mg in Cycle 1 followed by IV decitabine at 20 mg/m 2 in Cycle 2), or Sequence B: (IV decitabine in Cycle 1 followed by oral decitabine/cedazuridine in Cycle 2). We conducted an intra-patient comparison of decitabine PK (primary PK endpoint: decitabine AUC equivalence over 5 days of dosing). Cycles were repeated every 28 days (unless delays were needed). All patients received oral decitabine/cedazuridine in Cycles 3 and above until disease progression or unacceptable toxicity. Patients were eligible per the FDA-approved label of IV decitabine (MDS patients by FAB classification including CMML, or MDS IPSS Intermediate-1, 2 or high-risk patients). Clinical endpoints were best response according to International Working Group (IWG) 2006 response criteria, transfusion independence for at least 8 or 16 consecutive weeks, overall survival, and safety. Adverse events (AEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Results: Of the 133 patients enrolled and treated in ASCERTAIN, 16 (12%) had a diagnosis of CMML with demographics and as follows: median age 71.5 years, 69% Male/31% Female, median weight 87kg (range 65-124), 25% ECOG 0, 75% ECOG 1. Population disease characteristics were: 19% poor or intermediate risk cytogenetics, with median baseline hemoglobin 90 g/L, neutrophils 1.27 X 10 9/L, platelets 84 x 10 9/L, bone marrow blasts 5%, with 38% RBC transfusion dependent. Patients received a median of 7 cycles of therapy (range 3-24). Treatment-emergent adverse events of CTCAE Grade 3 or higher in > 10% of patients, independent of relationship to ASTX727, were cytopenias (neutropenia [69%], thrombocytopenia [63%], anemia [56%], leukopenia [19%]), febrile neutropenia (31%), fatigue (13%). Two patients (12.5%) had Complete Responses (CR), 8 (50%) had marrow CR ([mCR], including 3 (19%) with hematologic improvement (HI);Overall Response rate (ORR) [CR + PR+ mCR + HI] was 75%. Of six patients with baseline RBC transfusion dependence 3 (50%) became transfusion independent. Leukemia-free survival was 28.2 months and after a median follow up of more than 33 months, median overall survival had not been reached. Two patients (13%) went on to Hematopoietic Stem Cell Transplant (HCT). Conclusions: In the overall study, oral decitabine/cedazuridine delivered equivalent PK exposure to 5 days of IV decitabine 20mg/m 2 with a resultant clinical activity safety and efficacy profile in CMML patients consistent with the published literature (e.g Zeidan, et a 2017) and the Phase 2 experience. The use of oral decitabine/cedazuridine is a reasonable approach in CMML patients. References: Garcia-Manero, et al ASH 2019 Savona, et al, Int. MDS Symposium, 2021 Zeidan, et al, Cancer 2017: 3754-3762. [Formula presented] Disclosures: Savona: Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees;CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees;BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees;Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;ALX Oncology: Research Funding;Astex: Research Funding;Incyte: Research Funding. McCloskey: Pfizer: Consultancy;Takeda: Consultancy, Speakers Bureau;Incyte: Speakers Bureau;Novartis: Consultancy;COTA: Other: Equity Ownership;BMS: Honoraria, Speakers Bureau;Amgen: Speakers Bureau;Jazz: Consultancy, Speakers Bureau. Griffiths: Boston Biomedical: Consultancy;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria;Taiho Oncology: Consultancy, Honoraria;Genentech: Research Funding;Astex Pharmaceuticals: Honoraria, Research Funding;Takeda Oncology: Consultancy, Honoraria;Novartis: Honoraria;Apellis Pharmaceuticals: Research Funding;Alexion Pharmaceuticals: Consultancy, Research Funding. Yee: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Forma Therapeutics: Research Funding;Geron: Research Funding;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;AbbVie: Honoraria;Janssen: Research Funding;Onconova: Research Funding;Genentech: Research Funding;Otsuka: Membership on an entity's Board of Directors or advisory committees;MedImmune: Research Funding;Jazz: Research Funding;Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding;Tolero: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Paladin: Membership on an entity's Board of Directors or advisory committees. Zeidan: BeyondSpring: Consultancy;Janssen: Consultancy;Boehringer Ingelheim: Consultancy, Research Funding;BioCryst: Other: Clinical Trial Committees;AstraZeneca: Consultancy;Pfizer: Other: Travel support, Research Funding;Kura: Consultancy, Other: Clinical Trial Committees;Incyte: Consultancy, Research Funding;Ionis: Consultancy;Daiichi Sankyo: Consultancy;Epizyme: Consultancy;Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding;Loxo Oncology: Consultancy, Other: Clinical Trial Committees;Genentech: Consultancy;Geron: Other: Clinical Trial Committees;Cardiff Oncology: Consultancy, Other: Travel support, Research Funding;BMS: Consultancy, Other: Clinical Trial Committees, Research Funding;Gilead: Consultancy, Other: Clinical Trial Committees;Aprea: Consultancy, Research Funding;Astellas: Consultancy;Astex: Research Funding;Jazz: Consultancy;Jasper: Consu tancy;Amgen: Consultancy, Research Funding;Agios: Consultancy;ADC Therapeutics: Research Funding;Acceleron: Consultancy, Research Funding;AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Al-Kali: Novartis: Research Funding;Astex: Other: Research support to institution. Patel: Agios: Membership on an entity's Board of Directors or advisory committees;Celgene-BMS: Membership on an entity's Board of Directors or advisory committees;PVI: Honoraria. Sabloff: Takeda: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees;Astellas: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Jaxx: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;ROCHE: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees. Dao: Astex Pharmaceuticals, Inc.: Current Employment. Fazal: Janssen Oncology: Consultancy, Honoraria, Speakers Bureau;Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Gilead Sciences: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;Agios: Consultancy, Honoraria, Speakers Bureau;Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau;Takeda: Consultancy, Honoraria, Speakers Bureau;Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau;AMGEN: Consultancy, Honoraria, Speakers Bureau;Incyte: Consultancy, Honoraria, Speakers Bureau;Jazz Pharmaceuticals:Consultancy, Honoraria, Speakers Bureau;Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau;Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau;Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau. Odenike: Celgene, Incyte, AstraZeneca, Astex, NS Pharma, AbbVie, Gilead, Janssen, Oncotherapy, Agios, CTI/Baxalta, Aprea: Research Funding;AbbVie, Celgene, Impact Biomedicines, Novartis, Taiho Oncology, Takeda: Consultancy. Kantarjian: Ipsen Pharmaceuticals: Honoraria;Astra Zeneca: Honoraria;Astellas Health: Honoraria;Aptitude Health: Honoraria;Pfizer: Honoraria, Research Funding;Novartis: Honoraria, Research Funding;Jazz: Research Funding;Immunogen: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Ascentage: Research Funding;Amgen: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;KAHR Medical Ltd: Honoraria;NOVA Research: Honoraria;Precision Biosciences: Honoraria;Taiho Pharmaceutical Canada: Honoraria. DeZern: Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roboz: Janssen: Research Funding;AbbVie: Consultancy;Actinium: Consultancy;Agios: Consultancy;Amgen: Consultancy;Astex: Consultancy;Astellas: Consultancy;AstraZeneca: Consultancy;Bayer: Consultancy;Blueprint Medicines: Consultancy;Bristol Myers Squibb: Consultancy;Celgene: Consultancy;Daiichi Sankyo: Consultancy;Glaxo SmithKline: Consultancy;Helsinn: Consultancy;Janssen: Consultancy;Jasper Therapeutics: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Mesoblast: Consultancy;Novartis: Consultancy;Otsuka: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Busque: Novartis: Consultancy. Leber: Novartis: 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, peakers Bureau;BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: 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;TaiHo: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Otsuka: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hao: Astex Pharmaceuticals, Inc.: Current Employment. Keer: Astex Pharmaceuticals, Inc.: Current Employment. Azab: Astex Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees.

Oral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study

[Formula presented] Background/Introduction: Lower-risk (IPSS low risk and Int-1) myelodysplastic syndromes (MDS) are typically treated supportively to address cytopenias. DNA methyltransferase inhibitors (DNMTi) such as azacitidine and decitabine (DEC) are FDA-approved for higher risk MDS patients (pts), and while the DEC USPI includes IPSS Int-1 pts, it is not widely used in this population. Approved intravenous (IV) or subcutaneous (SC) regimens require 5-7 days of treatment every month burdening older cancer pts due to daily travel and treatment time and may increase potential risk from pandemic SARS-CoV-2 infection. Because DNMTis are rapidly degraded by cytidine deaminase (CDA) in the gut and liver, oral availability has only been recently possible. A randomized study with CC-486, an oral formulation of azacitidine, in the Int-1 population showed a median overall survival (mOS) of approximately 17 months for both placebo and treated patients (Garcia-Manero, 2021). Oral DEC 35 mg/cedazuridine 100 mg (ASTX727) or DEC-C, is an oral fixed dose combination (FDC) of DEC and the CDA inhibitor cedazuridine (CED) resulting in equivalent exposure (99%;90% CI 93% to 106%) to standard IV DEC 20 mg/m 2 for 5 days in an intra-patient randomized cross-over study (Garcia-Manero et al, ASH 2019). Here, we present data on patients with lower risk MDS from that study. Methods: We used a randomized cross over design with pts randomized 1:1 in the first 2 cycles to either Sequence A: (DEC 35 mg/ CED 100 mg in Cycle 1 and IV DEC at 20 mg/m 2 in Cycle 2), or Sequence B (IV DEC in Cycle 1 and oral DEC/CED in Cycle 2). Cycles were repeated every 28 days unless delays were needed, and all patients received oral DEC-C in Cycles 3+ until disease progression or unacceptable toxicity. We conducted an intra-patient comparison of DEC PK (DEC AUC equivalence over 5 days of dosing). Pts were eligible as per the FDA-approved label of IV DEC (MDS pts by FAB classification including CMML, or MDS IPSS Intermediate-1, 2 or high-risk pts). Clinical endpoints were best response as assessed by an independent expert panel according to IWG 2006 response criteria, transfusion independence (TI), overall survival (OS), and safety. Results: Of the 133 pts treated in ASCERTAIN, 69 had a diagnosis of lower-risk MDS (93% Int-1, 7% LR). Median age was 70.0 years (range 45-87), 65% were male, median weight was 84 kg (range 50-127), median baseline hematologic parameters were: hemoglobin 89 g/L (range 69.8-146.5), WBCs 1.50 X 10 9/L (range 0.11-7.1), platelets (plt) 86 x 10 9/L (range 5-703), bone marrow blasts 4% (range 0-18), cytogenetics: 7 (10.1%) poor-risk, 21 (30.4%) intermediate risk, 37 (53.6%) better-risk, 4 (5.7%) missing or not evaluable. 27(39%) of the pts were RBC transfusion dependent (TD) and 6 (9%) plt TD. 17 (25%) had received prior MDS treatment, 3% prior DNMTi. Pts received a median of 9 cycles of therapy (range 1-28). Treatment-emergent adverse events of CTCAE Gr 3 or higher in >10% of pts, independent of relationship to ASTX727, included cytopenias (neutropenia [59%], thrombocytopenia [58%], anemia [48%], leukopenia [26%]), febrile neutropenia (32%), and pneumonia (19%). Sixteen pts (23%) achieved Complete Response (CR), 18 (26%) had marrow CR (mCR), including 9 (13%) with hematologic improvement (HI). Overall Response rate (ORR;CR + PR+ mCR + HI) was 57%. Of those RBC or plt TD at baseline, 13 (48%) became RBC TI and 4 (67%) became plt TI. With approximately 32 months of median follow up, neither median leukemia-free survival (mLFS) nor mOS had been reached (Figure 1). Twelve pts (17%) went on to allogeneic stem cell transplant. Conclusions: Oral decitabine/cedazuridine given as a FDC in MDS pts produced equivalent PK exposure to 20 mg/m 2 IV DEC;in lower risk MDS pts with treatment indicated, the agent was generally well-tolerated with prolonged treatment and could result in mLFS and mOS which exceeds 32 months. This FDC and other dosing regimens of oral DEC-C should be further studied in this patient population. References: Garcia-Mane o, et al, ASH 2019 Savona, et al, Int. MDS Symp. 2021 Garcia-Manero, et al, Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients with Lower-Risk Myelodysplastic Syndromes. J.Clin.Onc. 2021 39:13, 1426-1436 [Formula presented] Disclosures: McCloskey: Pfizer: Consultancy;Jazz: Consultancy, Speakers Bureau;COTA: Other: Equity Ownership;Incyte: Speakers Bureau;Takeda: Consultancy, Speakers Bureau;Novartis: Consultancy;BMS: Honoraria, Speakers Bureau;Amgen: Speakers Bureau. Griffiths: Alexion Pharmaceuticals: Consultancy, Research Funding;Abbvie: Consultancy, Honoraria;Taiho Oncology: Consultancy, Honoraria;Genentech: Research Funding;Novartis: Honoraria;Takeda Oncology: Consultancy, Honoraria;Astex Pharmaceuticals: Honoraria, Research Funding;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Apellis Pharmaceuticals: Research Funding;Boston Biomedical: Consultancy. Yee: Paladin: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Genentech: Research Funding;Geron: Research Funding;Janssen: Research Funding;Jazz: Research Funding;MedImmune: Research Funding;Onconova: Research Funding;Tolero: Research Funding;AbbVie: Honoraria;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;Otsuka: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Forma Therapeutics: Research Funding;Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zeidan: Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding;Genentech: Consultancy;Ionis: Consultancy;Astellas: Consultancy;Epizyme: Consultancy;AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding;Jasper: Consultancy;Cardiff Oncology: Consultancy, Other: Travel support, Research Funding;BeyondSpring: Consultancy;Loxo Oncology: Consultancy, Other: Clinical Trial Committees;Janssen: Consultancy;Acceleron: Consultancy, Research Funding;AstraZeneca: Consultancy;Kura: Consultancy, Other: Clinical Trial Committees;Gilead: Consultancy, Other: Clinical Trial Committees;Agios: Consultancy;Daiichi Sankyo: Consultancy;Boehringer Ingelheim: Consultancy, Research Funding;Geron: Other: Clinical Trial Committees;BMS: Consultancy, Other: Clinical Trial Committees, Research Funding;BioCryst: Other: Clinical Trial Committees;Pfizer: Other: Travel support, Research Funding;Aprea: Consultancy, Research Funding;ADC Therapeutics: Research Funding;Jazz: Consultancy;Incyte: Consultancy, Research Funding;Amgen: Consultancy, Research Funding;Astex: Research Funding. Al-Kali: Astex: Other: Research support to institution;Novartis: Research Funding. Patel: Celgene-BMS: Membership on an entity's Board of Directors or advisory committees;PVI: Honoraria;Agios: Membership on an entity's Board of Directors or advisory committees. Sabloff: Pfizer: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Astellas: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;ROCHE: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Jaxx: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory ommittees;BMS: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees. Dao: Astex Pharmaceuticals, Inc.: Current Employment. Fazal: Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau;Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Janssen Oncology: Consultancy, Honoraria, Speakers Bureau;Incyte: Consultancy, Honoraria, Speakers Bureau;Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau;Gilead Sciences: Consultancy, Honoraria, Speakers Bureau;Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau;AMGEN: Consultancy, Honoraria, Speakers Bureau;Agios: Consultancy, Honoraria, Speakers Bureau;Takeda: Consultancy, Honoraria, Speakers Bureau. Odenike: AbbVie, Celgene, Impact Biomedicines, Novartis, Taiho Oncology, Takeda: Consultancy;Celgene, Incyte, AstraZeneca, Astex, NS Pharma, AbbVie, Gilead, Janssen, Oncotherapy, Agios, CTI/Baxalta, Aprea: Research Funding. Kantarjian: AbbVie: Honoraria, Research Funding;Novartis: Honoraria, Research Funding;Ascentage: Research Funding;Pfizer: Honoraria, Research Funding;BMS: Research Funding;Daiichi-Sankyo: Research Funding;Amgen: Honoraria, Research Funding;Ipsen Pharmaceuticals: Honoraria;Jazz: Research Funding;Astellas Health: Honoraria;Immunogen: Research Funding;Astra Zeneca: Honoraria;Aptitude Health: Honoraria;KAHR Medical Ltd: Honoraria;NOVA Research: Honoraria;Precision Biosciences: Honoraria;Taiho Pharmaceutical Canada: Honoraria. DeZern: Takeda: Consultancy, Membership on an entity's Board of Directors or advisorycommittees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roboz: Novartis: Consultancy;Mesoblast: Consultancy;Jasper Therapeutics: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Daiichi Sankyo: Consultancy;Otsuka: Consultancy;Bristol Myers Squibb: Consultancy;Blueprint Medicines: Consultancy;Bayer: Consultancy;AstraZeneca: Consultancy;Astellas: Consultancy;Astex: Consultancy;Amgen: Consultancy;Agios: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Janssen: Research Funding;Celgene: Consultancy;Glaxo SmithKline: Consultancy;Helsinn: Consultancy;Janssen: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Busque: Novartis: Consultancy. Leber: Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Otsuka: 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;TaiHo: Honoraria, Membership on an entity's Board of Directors or advisory committees;AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;BMS: Honoraria, 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;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hao: Astex Pharmaceuticals, Inc.: Current Employment. Keer: Astex Pharmaceuticals, Inc.: Current Employment. Azab: Astex Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Savona: Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Cons ltancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees;CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees;Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;ALX Oncology: Research Funding;Astex: Research Funding;Incyte: Research Funding.

The Effect of the Presence of Lower Urinary System Symptoms on the Prognosis of COVID-19: Preliminary Results of a Prospective Study.

PURPOSE: To investigate the effectiveness of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), which occur as a natural result of aging and androgen exposure, in predicting disease prognosis in male patients diagnosed with COVID-19. METHODS: The study was planned prospectively. The study included 63 male patients over 40 years of age diagnosed with COVID-19. The patients were diagnosed with COVID-19 based on the results of reverse transcription polymerase chain reaction tests of oropharyngeal and nasopharyngeal swabs obtained as per the World Health Organization guidelines. The presence of LUTS was assessed by the International Prostate Symptom Score (I-PSS), a subjective assessment, and the I-PSS was filled for the patients included in the study. The patients were divided into three groups based on their scores in the I-PSS survey: group 1: mild (0-7), group 2: moderate (8-19), and group 3: severe (20-35). The data of all three groups were statistically analyzed. RESULTS: In the assessment performed between the groups, it was identified that for patients in group 3, the length of hospital stay was longer, intensive care requirement was more frequent, and their mortality rates were numerically higher. In the evaluation made regarding the time to intensive care admittance, this was identified to be the shortest in group 3. CONCLUSION: As a result of our study, we think that in patients with COVID-19, BPH-related LUTS can guide clinicians in predicting prognosis.