ABSTRACT
Background: The phase III EMERALD trial (NCT03778931) reported significantly prolonged progression-free survival (PFS) and a manageable safety profile with elacestrant vs SoC endocrine therapy (ET) in patients (N=478) with ER+/HER2- advanced or mBC following progression on prior CDK4/6i plus ET. PROs measuring quality of life (QoL) are reported here. Method(s): EMERALD patients (pts) completed 3 PRO tools at prespecified time points: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the EuroQoL 5 Dimension 5 Level (EQ-5D-5L). Result(s): The ratio of PROs tools completed vs. PROs tools expected was 80-90% through cycle 4 and approximately 70% at cycle 6;likely due to clinical study period overlapping with COVID-19 period. Overall, the EORTC QLQ-C30 scores were similar for elacestrant and SoC, with no differences across all time points for both functional and symptom scales. However, PRO-CTCAE results showed that fewer pts who received elacestrant reported very severe nausea (4.0% vs 14.3% by cycle 6) or very severe vomiting (9.1% vs 50% by cycle 6) compared with SoC. There were no clinically meaningful differences across all time points in adverse events typically observed with pts with cancer on ET, such as fatigue, nausea, vomiting, joint and muscle pain and hot flashes. EQ-5D-5L scores were generally comparable throughout treatment for both study arms, with elacestrant showing numerically better outcomes vs SoC for mobility, self-care and usual activities. Similar trends were observed for the full intent-to-treat population and in pts with detectable estrogen receptor 1 mutations (ESR1m). Conclusion(s): This analysis confirmed that QoL was maintained between treatment groups in the EMERALD trial. Together with the previously described statistically significant prolonged PFS and manageable safety profile, these PRO results provide additional evidence that oral elacestrant is clinically meaningful in this patient population with limited therapeutic options. Clinical trial identification: NCT03778931. Editorial acknowledgement: Jeffrey Walter, IQVIA. Legal entity responsible for the study: Stemline Therapeutics/Menarini Group. Funding(s): Stemline Therapeutics/Menarini Group. Disclosure: J. Cortes: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics;Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo;Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies;Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics;Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London;Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. F.C. Bidard: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Lilly, Novartis, Radius Health, Menarini;Financial Interests, Institutional, Advisory Role: Menarini;Financial Interests, Personal, Speaker's Bureau: Pfizer, Novartis, AstraZeneca, Roche, Lilly, Rain Therapeutics;Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Menarini Silicon Biosystems, Prolynx;Financial Interests, Institutional, Other, patents: ESR1 & MSI detection techniques;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Pfizer, AstraZeneca, Novartis. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisa , Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead;Financial Interests, Personal, Royalties: UpToDate;Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.;Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. V.G. Kaklamani: Financial Interests, Personal, Other, Honoraria: Genentech, Novartis, Pfizer, Genomic Health, Puma Biotechnology, AstraZeneca, Seattle Genetics, Daichi, Gilead Sciences;Financial Interests, Personal, Advisory Role: Amgen, Eisai, Puma Biotechnology, Celldex, AstraZeneca, Athenex, bioTheranostics;Financial Interests, Personal, Speaker's Bureau: Genentech, Novartis, Genomic Health, Puma Biotechnology, Pfizer, AstraZeneca/Daiichi Sankyo;Financial Interests, Personal, Research Grant: Eisai. I. Vlachaki: Financial Interests, Personal, Full or part-time Employment: Menarini Hellas A.E. G. Tonini: Financial Interests, Personal, Full or part-time Employment: Menarini Ricerche S.p.A. N. Habboubi: Financial Interests, Personal, Full or part-time Employment: Stemline Therapeutics;Financial Interests, Personal, Leadership Role: Stemline Therapeutics. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly;Financial Interests, Personal, Invited Speaker: Synthon, Amgen;Financial Interests, Institutional, Research Grant: Roche.Copyright © 2023
ABSTRACT
Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.
ABSTRACT
Background: Biweekly infusions with alglucosidase alfa (recombinant human alpha-glucosidase), are the cornerstone of treatment in late onset Pompe disease. Home infusion therapy may improve quality of life. In many countries providing enzyme replacement therapy (ERT) at home is not possible due to safety concerns related to the risk of infusion associated reactions (IARs) or logistical constraints. The COVID-19 pandemic has prompted the need to provide ERT for Pompe patients at home. In the Netherlands, currently over 80% of infusions are given at home. Here we present data on the safety of homebased infusions in adult patients with late-onset Pompe disease (LOPD). Methods: Data on patient descriptives, infusion characteristics and IARs from patients starting ERT between 1999 and 2018 were collected and analyzed. The Dutch infusion schedule for adult lateonset patients differs from the schedule recommended by the pharmaceutical company and is as follows: 0.2, 0.8, 3.5, 10 mg/kg/hour with steps of 30 minutes for the first three steps and 10 mg/kg/ hour for the remainder of the infusion. IARs were graded by the healthcare provider. If no classification was available infusions were retrospectively classified using the Common Terminology Criteria for Adverse Events (CTCAE) classification. Descriptive analyses were performed tabulating patient and infusion characteristics as well as types of IARs and actions needed to resolve these. Results: Data on 18380 infusions with alglucosidase alfa in 121 adult LOPD patients were analysed. 4961 infusions (27.0 %) were given in hospital and 13419 (73.0 %) at home. The majority of infusions (88.4%) was administered using a standard infusion schedule. In 144 (2.9%) of hospital infusions and 113 (0.8%) of home infusions an IAR occurred. Mild IARs occurred in 115 hospital infusions and in 104 infusions at home. Twenty-five moderate IARs were reported in hospital and 8 at home. Very few severe IARs occurred (4 in hospital, 1 at home). The most prevalent symptoms in hospital were itching and chills;at home chills and trembling were most prevalent. The most common most severe interventions taken in hospital in response to an IAR were giving medication (antihistamines), or pausing the infusion and restarting it later. This was also the most common intervention at home. Sixteen infu-sions (11.1%) in hospital and 6 infusions (5.3%) at home were stopped completely after the IAR occurred. Only one IAR in the home situation required immediate clinical evaluation in hospital. The consecutive infusion after an IAR occurred in hospital, patients most commonly received premedication or the infusion scheme was adapted, whereas at home after the majority of IARs no action was taken. The most common premedication in hospital were an antihistamine and a corticosteroid and at home an antipyretic and antihistamine were most common. Conclusion: Our data demonstrate that very few IARs occur during alglucosidase alfa infusions in adult patients with LOPD. Very few severe IARs occurred. The majority of IARs at home were mild and did not require additional medical intervention. This demonstrates that alglucosidase alfa can be safely administered in the home situation, provided the appropriate infrastructure is present.
ABSTRACT
Background: Immunotherapy can boost a patient's immune system to bring about anti-tumor activity and may theoretically exaggerate the inflammatory immune response to infection or vaccinations. Conversely, vaccination may enhance immune activity in patients on immunotherapy. Currently, there are limited safety data in patients treated with immunotherapy who received COVID-19 vaccines. Methods: An IRB-approved retrospective review of Dana-Farber Cancer Institute patients treated with PD-1 checkpoint inhibitors and received COVID-19 vaccines was performed. The primary endpoint was the incidence rate of immune-related adverse events (irAEs) pre-and post-COVID-19 vaccinations. An Electronic Health Record search identified all patients who completed COVID-19 vaccines between 12/1/2020 and 3/31/2021 and received anti-PD-1 monotherapy between 10/1/2020 and 5/31/2021. Medical record review identified timing, occurrence, and grading of irAEs as defined by clinicians or Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: A total of 229 patients were included in the study. The most common underlying cancers were lung (32%) and melanoma (26%). The majority of patients had Pfizer-BioNTech COVID-19 vaccine;64% of all patients received the third dose of vaccine. The median duration of treatment was 15 months, and median duration of follow-up was 19 months. Among the study cohort, 120 irAEs occurred before vaccination (any grade);30 (25%) were grade 1, 35 (29%) were grade 2, 11 (9%) were grade 3 or 4, and 44 (37%) were ungraded. The main types of irAEs were skin toxicities (37% of all irAEs) followed by thyroid dysfunction (22%) and colitis (11%). Of the 75 irAEs that occurred after vaccination, 24 (32%) were grade 1, 16 (21%) were grade 2, 16 (21%) were grade 3 or 4, and 19 (26%) were ungraded. The main irAEs types were skin toxicity (31% of all irAEs) followed by thyroid dysfunction (13%) and hepatic toxicity (12 %). The all-grade pre-and post-vaccine irAE incidence rates per 100 patient-months were 4.13 and 5.09, respectively. Within this cohort, there were 0.96 (95% CI -0.362-2.284, p = 0.15) more irAEs post vaccine per 100 patient-months of anti-PD-1 therapy. Conclusions: The data weakly suggested that there is a higher incidence of irAEs post COVID-19 vaccine;however, the comparison did not achieve statistical significance. Further analysis of other patient characteristics will help to determine if any specific patterns are observed.
ABSTRACT
Background: Rituximab (anti-CD20 Ab) is the cornerstone of the treatment of non-Hodgkin B lymphomas. Infusion-related reactions (IRR) are the most common adverse effects. To reduce them, intravenous premedication with antihistamine and acetaminophen is administered prior to rituximab. If no IRR after first infusion, subsequent infusions time takes 3-6 hours. Many centers use the rapid 90-minute infusion (off-label). Since 2017 subcutaneous rituximab formulation is available, that takes 5 minutes of administration. Nevertheless, in order to reduce cost, due to approval of biosimilars, some health providers continue using intravenous rituximab. On the other hand, with COVID pandemic, an effort to reduce visits and day-care hospitals stays has been made. In the current situation, it would be convenient to reduce day-care stay and the nursing care burden. We wanted to evaluate the safety of an ultrarapid infusion of biosimilar rituximab in a total time of 30 minutes by analyzing IRR and adverse events (AE). Methods: Since November 2021, 3 cohorts of ultrafast infusion have been studied as follows: One cohort (Cohort 1) with intravenous premedication with dexchlorpheniramine and acetaminophen, followed by rituximab infusion over 1 hour, and 2 cohorts with rituximab infusion over 30 minutes: Cohort 2: with intravenous premedication, and cohort 3 with oral premedication. IRR and adverse events have been independently reviewed and graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (November 27, 2017). Results: 34 patients have been included receiving 48 rituximab infusions (16 infusions in each cohort). Median age was 64 years old (range: 51-91). Diagnostic of NHL were as follows: large b cell: 10;follicular: 13;marginal: 7;mantle cell: 1, Waldeström: 1;Ritcher transformation: 2. Rituximab infusion was in monotherapy (21), and in combination (27) with: bendamustine: 9, CHOP: 17, GEMOX: 1. Considering safety, no IRR has been observed in cohort 1 (1 hour infusion), and 1 IRR grade II in cohort 3 (30 minutes, oral premedication). Other AE were: hypertension grade I and hypotension grade I, both in cohort 2. Conclusions: Ultrarapid rituximab infusion is safe. Oral premedication is feasibly allowing a total infusion time of 30 minutes. This infusion rate alleviates day-care burden saving between 75-90% of time in each rituximab infusion, reduce day-care stay and is comfortable for the patients.
ABSTRACT
Purpose or Objective We designed a hypofractionated radiotherapy protocol for adjuvant or salvage treatment after radical prostatectomy. In this first report we present the implementation of this protocol in the context of a COVID-19 pandemic. Materials and Methods Patients meeting the inclusion criteria (high-risk features on histopathology or biochemical recurrence) received radiotherapy to the prostate bed 51 Gy in 17 fractions, elective treatment of the pelvis at a dose of 36 Gy in 12 fractions was permited. Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events versión 4.03. The disease-related quality of life, urinary, gastrointestinal, sexual and hormonal function were evaluated with the Expanded Prostate Cancer Index Composite (EPIC), QLQc30 and PR25 questionnaires at baseline before the start of radiotherapy and at one month after radiotherapy, then every six monts for two years. In addition, the incidence of COVID-19 cases was reported in the patients recruited in the trial and in those who underwent standard fractionation treatment (1.8-2.0 Gy per fraction), and in health personnel involved in the treatment of patients in study period. Results From August 2020 to March 2021, 22 patients have been registered. Fourteen patients have completed treatment and are included in this report. The median age was 64 years and most had a Gleason 3 + 4 (50%), with a pT3a (35.7%) and negative surgical margins (71.4%). Three patients (21.4%) were staged as pN1. Most patients were treated for salvage (57.1%), with an median PSA prior to the start of RT of 0,29 ng/ml. Most patients report minimal or low acute radiation effects in terms of GI and GU toxicity, with an acute toxicity grade 2 GI and GU of 50% and 14.3%, respectively. Without Grade 3 or higher GI / GU toxicity. Of the 14 patients who received the trial protocol, none had a clinical of COVID-19 infection, while one patient who received treatment with conventional fractionation development a COVID-19 infection. Conclusion We present the implementation of an protocol of hypofractionated schedule of postoperative prostate radiotherapy in an academic center in a developing country in the context of a COVID-19 pandemic. Preliminary results show the absence of COVID infection in the included patients, and low GU and GI toxicity.
ABSTRACT
Background: Tocilizumab is a humanized monoclonal antibody that targets Interleukin-6 receptors. Recent trials have shown that tocilizumab may be effective against COVID-19. It is also known that tocilizumab may be associated with mild aminotransferase elevation, however, there are very limited data on hepatotoxicity of tocilizumab in patients with COVID- 19. Here we report our institutional experience on the development of liver injury after tocilizumab use in hospitalized patients with COVID-19. Methods: We analyzed all consecutive adult hospitalized patients who had PCR confirmed COVID-19 and were admitted to our hospital network between January 1st, 2021, and November 15th, 2021. To be considered eligible for inclusion patients should had an admission liver injury panel and at least one additional follow-up panel before discharge. Patients with baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times of the upper normal limit were excluded. Liver injury was measured by ALT, AST, or total bilirubin elevation. Grading was based on the Common Terminology Criteria for Adverse Events version 5.0. The primary outcome of interest was to estimate the incidence of liver injury among patients who received tocilizumab. As a secondary outcome, we examined the association of all-grade liver injury with tocilizumab use by utilizing a multivariate logistic regression model adjusted for demographics, comorbidities, Remdesivir use, and baseline COVID-19 severity based on the NEWS score. Results: Among 1409 consecutive hospitalized patients who met the inclusion criteria, we identified 87 patients who received tocilizumab. Baseline patient characteristics are depicted on Table 1. We found that the incidence of any grade AST elevation was higher in the tocilizumab versus non-tocilizumab group (24.1% vs 13%;p=0.015), with similar findings in ALT (32.1% vs 18%;p=0.016) and bilirubin (18% vs 4.5% p<0.001) (Table 2). Likewise, in our multivariate logistic regression model, patients who received tocilizumab were more likely to have had elevated ALT (OR 2.16;95% CI: 1.31-3.55), AST (OR 2.56;95% CI: 1.48-4.43), or bilirubin (OR 3.30;95% CI: 1.57-6.92), compared to those who did not receive the drug. Conclusion: While tocilizumab is frequently utilized in the treatment of COVID-19 patients, few studies have evaluated its hepatotoxic potential in this population. Based on our institutional experience, tocilizumab use in hospitalized patients with COVID-19 is associated with ALT, AST, and bilirubin elevation even after adjusting for COVID-19 severity. However, the majority of hepatic injury events were graded as level I (mild injury) and severe hepatotoxicity was rare. Further studies are needed to confirm these findings, while monitoring of hepatic function after tocilizumab use is warranted, especially in patients with chronic liver disease. (Table Presented)
ABSTRACT
Introduction: Human steroid 5α-reductase 2 (SRD5A2) coded by SRD5A2 gene is an enzyme that catalyzes the reduction of testosterone to dihydrotestosterone. Dutasteride, an SRD5A2 inhibitor, is a widely used antiandrogen for the treatment of benign prostate hyperplasia. Multiple variations have been identified in the SRD5Ar gene. Some of these variations may affect the efficacy and safety of SRD5A2 inhibitors. Dutasteride has also been investigated for intermediate and high-risk nonmuscle- invasive urothelial bladder cancer treatment with the combination of BCG (Bacillus Calmette-Guerin). Objectives: The study aims to evaluate the potential impact of V89L (rs523349) and A49T (rs9282858) variations on the SRD5A2 gene on dutasteride efficacy and safety in bladder cancer patients that have been enrolled in Phase 2 clinical trial entitled 'Efficacy and safety of a 5-alpha reductase inhibitor, dutasteride, added to Bacillus Calmette Guerin (BCG) immunotherapy in the prevention of recurrence and progression of intermediate and high risk non-muscle invasive bladder cancer: A single-arm, Phase 2 clinical trial' Methods: Twenty-one patients on BCG and dutasteride in the Phase 2 clinical trial were included in the study. Genomic DNA was obtained from whole blood samples, and evaluation of V89L (rs523349) (G>C) and A49T (rs9282858) (C>T) variations on the SRD5A2 gene was performed by using TaqMan SNP Genotyping Assay. The severity of the adverse events was graded by the United States National Cancer Institute- Common Terminology Criteria for Adverse Events 5.0. The causality assessment of adverse drug reactions was performed using Liverpool Causality Assessment Tool, Naranjo Algorithm, and World Health Organization-Uppsala Drug Monitoring Centre Causality Assessment System. The response to dutasteride was evaluated as the presence of bladder cancer recurrence. The Chi-Square test was used for testing the relationship between categorical variables. P values of <0.05 were considered significant. Results: All patients were homozygous GG for V89L variation on the SRD5A2 gene. Regarding the A49T variation, only one patient was homozygous CC, 8 patients were homozygous TT and 12 patients were heterozygous TC. One of the 8 patients (%12) was homozygous TT and 3 of 12 patients (%25) were heterozygous TC had bladder cancer recurrence. There was no statistically significant difference between bladder cancer recurrence and A49T variation (p=0.803). None of the adverse events were associated with dutasteride treatment whereas some of the adverse events, mostly urinary tract infections, were associated with the BCG. Other adverse events were upper respiratory tract infections, COVID-19, abdominal pain, vomiting, and loss of appetite. Serious adverse events were coronary artery disease, dyspnea, hypotension, and urethral stricture. None of the serious adverse events were associated with dutasteride or BCG treatment. Conclusion: Neither V89L nor A49T variation on the SRD5A2 gene was found to be associated with the efficacy and safety of dutasteride in medium and high-risk bladder cancer patients. Further studies of these variations with larger sample sizes and/or healthy control groups may lead to a better understanding of the impact of these variations on the efficacy and safety of dutasteride.
ABSTRACT
Objective: To evaluate the frequency of infusion-related reactions (IRRs) and PROs following administration of ocrelizumab (OCR) as a 2-hour home infusion. Background: Home-based infusion of multiple sclerosis (MS) drugs may be a safe and convenient treatment during the SARS-CoV-2 pandemic. Design/Methods: 100 MS patients from Rocky Mountains MS Center who fulfill these criteria: 18-55 years;relapsing or primary progressive MS;completed first 600-mg dose of OCR;had neurologist-approved-therapy-monitoring labs;resided in area with 911 access;completed PROs in English;and no >/Grade 3 IRR in prior infusions. Patients completed majority of study visits in home or via telehealth. Primary outcome is IRRs with common terminology criteria for adverse events (CTCAE) collected at the infusion visit, 24 hours post-infusion, and 2 weeks post infusion via telehealth. Patients were asked to compare their home infusion vs last OCR infusion using PROs measuring infusion experience, nurse responsiveness and confidence in receiving a home infusion. Standard statistical methods were used for proportions and change scores. Results: Currently 51/100 patients have received a home infusion. Mean age of 42.5 years (SD +/ - 8.34);73% female;89% white;96% with relapsing MS;mean MS duration 8.8 years;3.3 years on OCR. Only 15.70% (95% CI: (7.02%, 28.59%) experienced an IRR, all classified as Grade 1. CTCAEs were self-reported in 82.35% of patients. Most common by occurrence were fatigue (n=21), itching (n=19), headache/migraine (n=10) and tingling (n=9). No SAEs were reported. These PROs showed improvements pre vs post home infusion (range 1-5, higher is better): nurses explained things clearly (pre=3.78, post=3.94;p=0.01);confidence in nurses administering infusion (pre=4.40, post=4.67;p=0.02);felt safe and respected during infusion (pre=4.45, post=4.69;p=0.03);felt comfortable in surroundings (pre=3.98;post=4.65;p<0.0001);worries about safety and AEs decreased (pre=3.75;post=4.16;p=0.008). Conclusions: Interim analysis of OCR home infusion safety and experience is encouraging.
ABSTRACT
Introduction: Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy expressing two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies. The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) is assessing cilta-cel in patients (pts) with multiple myeloma (MM) under various clinical settings and evaluating the suitability of outpatient administration. Updated results of CARTITUDE-2 cohort A are presented here. Methods: Cohort A pts had progressive MM after 1-3 prior lines of therapy (LOT;included proteasome inhibitor [PI] and immunomodulatory drug [IMiD]), were lenalidomide-refractory, and had no previous exposure to BCMA-targeting agents. A single cilta-cel infusion at a target dose of 0.75×106 CAR+ viable T cells/kg was given 5-7 d after start of lymphodepletion (cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 d). The primary endpoint was minimal residual disease (MRD) negativity at 10-5 at any time point. Secondary endpoints were overall response rate (ORR), duration of response (DOR), time and duration of MRD negativity, and incidence and severity of adverse events (AEs). Response was assessed per International Myeloma Working Group criteria and AEs were graded by Common Terminology Criteria for Adverse Events version 5.0 (cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS] by American Society for Transplantation and Cellular Therapy). Results: As of April 15, 2021 (median follow-up of 9.7 mo), 20 pts (65% men;median age 60 y [range 38-75]) received cilta-cel, with 1 pt treated in an outpatient setting. Pts had a median of 2 prior LOT (range 1-3);60% had 1-2 prior LOT and 40% had 3 prior LOT. All pts were exposed to a PI, IMiD, and dexamethasone;95% were exposed to alkylating agents and 65% to daratumumab. 95% of pts were refractory to last LOT;40% were triple-class refractory. ORR was 95% (95% CI 75.1-99.9);85% (95% CI 62.1-96.8) had ≥complete response (CR), and 95% (95% CI 75.1-99.9) had ≥very good partial response (Figure). Median time to first response was 1.0 mo (range 0.7-3.3) and median time to ≥CR was 2.6 mo (range 0.9-7.9). Median DOR was not reached;progression-free survival (PFS) at 6 mo was 90% (95% CI 65.6-97.4). Of 13 MRD-evaluable pts, 92.3% (95% CI 64.0-99.8) were MRD-negative at 10-5. Hematologic AEs (≥20% of pts) were neutropenia (95%;grade [gr] 3/4: 95%), thrombocytopenia (80%;gr 3/4: 35%), anemia (75%;gr 3/4: 45%), lymphopenia (65%;gr 3/4: 60%) and leukopenia (55%;gr 3/4: 55%). 95% of pts had CRS (gr 3/4: 10%);median time to onset was 7 d (range 5-9) and median duration was 4 d (range 2-11). Four pts (20%) had CAR-T neurotoxicity (all gr 1/2). Three pts (15%) had ICANS (all gr 1/2);median time to onset was 8 d (range 7-10) and median duration was 3 d (range 1-3). One pt had facial paralysis (gr 2) with time to onset of 29 d and duration of 51 d. No movement and neurocognitive treatment-emergent adverse events (TEAEs) were reported. One death due to COVID-19 was assessed as treatment-related. Safety was manageable in the pt treated in an outpatient setting. Conclusions: A single cilta-cel infusion led to early and deep responses in pts with MM who had 1-3 prior LOT and were lenalidomide-refractory. No movement and neurocognitive TEAEs occurred, suggesting successful implementation of monitoring and pt management strategies across phase 2/3 studies in the CARTITUDE program.
ABSTRACT
Dasatinib, a second-generation BCRABL1 tyrosine kinase inhibitor (TKI), is an approved treatment for chronic myeloid leukaemia, both as first-line therapy and following imatinib intolerance or resistance. It is generally well tolerated, however, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors and outcomes of this significant side effect were analysed in the phase 3 DASISION and 034/Dose-optimization trials. Annual risk of 5%-15% was reported. Drug-related pleural effusion occurred in 28%-33% of patients in a minimum of 5-year follow-up period. One major risk factor was advanced age. We therefore reviewed a cohort of 34 patients treated with dasatinib between 2016 and 2021, to determine 'real-world' data of this toxicity. Case notes, pathology results and radiological reports were analysed. We identified 12 (35%) cases of pleural effusions. Eight (66%) cases were male. The median average age of patients with and without drug-related pleural effusion were 59.5 years (range: 31-91 years) and 54.5 years (range: 20-88 years) respectively. Cardiovascular and respiratory comorbidities were noted in eight patients (66.6%) with pleural effusion (ischaemic heart disease, hypertension, lung cancer, COVID, peripheral vascular disease and hyperlipidaemia) and nine patients (41%) without pleural effusion (prior non-TKI pleural effusion, hypertension, asthma, congenital heart defect, COPD and atrial fibrillation). Nine cases (75%) of those with pleural effusion were non-smokers. Lymphocytosis was not noted in any of those 12 cases of drug-related pleural effusion. Ten cases (83%) were on dasatinib 100 mg daily when pleural effusion was diagnosed, one was on 50 mg daily and the other was on 20 mg daily. Pleural effusion occurred after a median of 36 months (range: 6-108 months). Nine cases (75%) were mild to moderate in severity-Common Terminology Criteria for Adverse Events (CTCAE ) grade 1-2, two were grade 3 and one was grade 4. Two required no intervention, three required only medical intervention (steroid+/-antibiotics), three required pleural tap and three required pleural drain. One required VATS procedure with talc pleurodesis. The patient with grade 1 pleural effusion required no treatment change. One required dose reduction of dasatinib without interruption. One required temporary interruption but restarted on the same dose. Six required temporary interruption of dasatinib followed by dose reduction to 50 mg daily. Two of these subsequently recurred on lower dose dasatinib and were then switched to an alternative TKI (bosutinib and imatinib). Two required temporary TKI interruption and were restarted on a different TKI (nilotinib). One case of pleural effusion persisted and the patient was kept off TKI treatment. Although the numbers are too small for statistically robust analysis, we have observed several trends which may help to guide patient counselling and selection. Pleural effusion has an incidence of 35% in our local population. Risk factors were cardiovascular and respiratory comorbidities, advanced age and male sex. Smoking status and lymphocytosis did not appear to be risk factors in our cohort, where they have been in other reports. Most effusions were mild to moderate in severity and could usually be managed by steroid+/-pleural tap+/-drain. Most patients required temporary interruption of their dasatinib but were successfully able to restart at a lower dose without recurrence..
ABSTRACT
Pegylated Interferon (PegIFN) is the recommended first-line cytoreductive therapy in patients aged <40 years with essential thrombocythaemia (ET) or polycythaemia vera (PV). However, its use in patients >60 years is often limited due to concerns about tolerability. In this study, we evaluate the efficacy and tolerability of PegIFN in patients >60 years at University College London Hospitals (UCLH). Using electronic medical records, we identified patients with ET, PV or myelofibrosis at UCLH who commenced treatment with PegIFN between 2010 and 2020 and were aged >60 years on starting therapy. Data were collected until April 2021 to allow a minimum of 1-year follow-up. Complete Haematological responses were defined as per standard European Leukaemia Net criteria. Adverse events (AE) were graded 1-5 according to Common Terminology Criteria for Adverse Events (CTCAE). Thrombosis risk was graded according to IPSET criteria for ET patients. Patients with PV were classed as high risk if they were aged >65 or had a previous history of thrombosis. Eighteen patients were included in the study. The median age was 75.1 years (range 63-91), 61% were female. Ten out of 18 (56%) had a diagnosis of ET, seven out of 18 (39%) of PV and 1/18 (6%) of post-ET myelofibrosis. Fifteen out of 18 (83%) were positive for JAK2 V617F, and two out of 18 (17%) were positive for CALR mutation. Ten out of 18 (56%) had significant cardiovascular co-morbidities at diagnosis. Five out of 18 (28%) had arterial or venous thromboembolic disease at diagnosis. Sixteen out of 18 (89%) were high-risk for thromboembolic events at diagnosis. Seventeen (94%) patients had PegIFN as a second-or thirdline agent. Of these, 15 out of 17 had received hydroxycarbamide (HU) as first-line therapy;two out of 17 had interferon alpha. PegIFN was started at a median age of 70 years (range 50-86) and continued for 5.7 years (range 2-13). Twelve out of 18 (67%) patients achieved complete remission (CR) on PegIFN monotherapy;1 out of 18 (6%) achieved CR on PegIFN and HU combination therapy, and the remaining 5 out of 18 (28%) achieved a partial remission (PR). The median time to CR was 5 months (range 1-40 months). Ten out of 18 (56%) had grade 1-2 AEs including skin rashes, cytopenia and fatigue. Three out of 18 (17%) developed a major thromboembolic event while on treatment (brachial artery embolism, transient ischaemic attack and a non-ST elevation myocardial infarction). Of these, two out of three failed to achieve a CR on PegIFN and required ongoing venesection. The third had suboptimal response due to dose escalation limited by grade 3 neutropenia. Thirteen patients (72%) remained on pegIFN at the end of the study period. Of those who discontinued, three out of five stopped due to cytopenias, one out of five died during the study period of Covid-19 infection and one out of five transformed to myelodysplastic syndrome. In this study, we present a group of patients who were at high risk for thrombosis due to their age and cardiovascular risk factors. The majority of AEs documented were grade 1-2, with only three out of 18 (17%) patients discontinuing due to AEs. The rate of CR 72% similar to that quoted in imminent studies including MPN-RC (Knudsen et al, 2018) and DALIAH trials (Mascarenhas et al, 2018), which recruited larger numbers of youngers ET and PV patients on PegIFN. Over 20% of MPN patients develop resistance or intolerance to HU (Sever et al, 2014);therefore, there is a need for alternative cytoreductive agents. Our study demonstrates PegIFN to be effective and well-tolerated for use in patients >60 years and is an excellent cytoreductive option in this cohort.
ABSTRACT
Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy expressing two B-cell maturation antigen (BCMA)-targeting, singledomain antibodies. The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating ciltacel in patients (pts) with multiple myeloma (MM) in various clinical settings and assessing the suitability of outpatient administration. Updated results from CARTITUDE-2 cohort A are presented here. Cohort A pts had progressive MM after 1-3 prior lines of therapy (LOT;included proteasome inhibitor [PI] and immunomodulatory drug [IMiD]), were lenalidomide-refractory, and had no previous exposure to agents targeting BCMA. A single cilta-cel infusion at a target dose of 0.75 × 106 CAR+ viable T cells/kg was given 5-7 days after start of lymphodepletion (cyclophosphamide [300 mg/m2 ] and fludarabine [30 mg/m2 ] for 3 days). The primary endpoint was minimal residual disease (MRD) negativity at 10 -5 at any time point. Secondary endpoints were overall response rate (ORR), duration of response (DOR), time and duration of MRD negativity and adverse events (AEs). Response was assessed by International Myeloma Working Group criteria and AEs were graded by Common Terminology Criteria for Adverse Events version 5.0 (cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS] by American Society for Transplantation and Cellular Therapy). As of April 15, 2021 (median follow-up 9.7 months), 20 pts (65% men;median age 60 years [range 38-75]) received ciltacel, with 1 pt treated in an outpatient setting. Pts had a median of two prior LOT (range 1-3);60% with 1-2 prior LOT and 40% with three prior LOT. All pts were exposed to a PI, IMiD and dexamethasone;95% were exposed to alkylating agents and 65% to daratumumab. 95% of pts were refractory to last LOT;40% were triple-class refractory. ORR was 95% (95% CI 75.1-99.9);85% (95% CI 62.1-96.8) had ≥complete response (CR), and 95% (95% CI 75.1-99.9) had ≥very good partial response. The median time to first response was 1.0 months (range 0.7-3.3) and the median time to ≥CR was 2.6 months (range 0.9-7.9). The median DOR was not reached;progression-free survival (PFS) at 6 months was 90% (95% CI 65.6-97.4). Of MRD-evaluable pts ( n = 13), 92.3% (95% CI 64.0-99.8) were MRD-negative at 10 -5 . Haematological AEs (≥20% of pts) were neutropenia (95%;grade [gr] 3/4: 95%), thrombocytopenia (80%;gr 3/4: 35%), anaemia (75%;gr 3/4: 45%), lymphopenia (65%;gr 3/4: 60%) and leukopenia (55%;gr 3/4: 55%). Ninety-five percent of pts had CRS (gr 3/4: 10%);median time to onset was 7 days (range 5-9) and median duration was 4 days (range 2-11). Four pts (20%) had CAR-T neurotoxicity (all gr 1/2). Three pts (15%) had ICANS (all gr 1/2);median time to onset was 8 days (range 7-10) and median duration was 3 days (range 1-3). One pt had facial paralysis (gr 2) with time to onset of 29 days and duration of 51 days. No movement and neurocognitive treatment-emergent adverse events (TEAEs) occurred. One death occurred due to COVID-19 (assessed as treatment-related). Safety was manageable in the pt treated in an outpatient setting. Lenalidomide-refractory pts with MM and 1-3 prior LOT showed early and deep responses with a single cilta-cel infusion. No movement and neurocognitive TEAEs were reported, suggesting utilisation of successful monitoring and pt management strategies across phase 2/3 studies in the CARTITUDE program.
ABSTRACT
Introduction: Infections are the primary or contributory cause of death in a third of all fatalities in CLL. The COVID-19 pandemic has entailed a significant reorganization of medical care for patients with hematological malignancies. The purpose of this work is to assess the impact of measures aimed at preventing SARS-CoV-2 infections on the incidence of other viral and bacterial infections in patients with CLL. Methods: Collection of infectious episodes: infections were divided into localization groups according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. In the structure of infectious complications, groups of typical bacterial, viral, fungal, and parasitic infections were identified. The rest of the infections were assigned to the mixed (undefined) group. We compared the frequency of infections in CLL patients before and after the introduction of COVID- 19 restrictive measures in Moscow (1st period: 1 April 2019-31 March 2020;2nd period: 1 April 2020-31 March 2021). Infections were assessed prospectively by calling each patient once a week. Diagnoses were confirmed via in-person visits and/or using the United Medical Information and Analytical System of Moscow. Statistical assessment of infections episodes frequency: the weekly and monthly incidence of infections were calculated for a cohort of patients at risk in a given period. The analysis included patients who started ibrutinib or venetoclax before 1 October 2019, and who were alive and continued treatment by 1 April 2020. Actual morbidity rate are compared to rates predicted by AutoRegressive Moving Average (ARMA) model trained on the data collected the year before pandemics. The number of hospital in-person visits: episodes of visits to medical institutions during the study period were collected retrospectively based on city-wide electronic health record (EHR) platform the Unified Medical Information and Analytical System (UMIAS), USA. Results: The study included 193 CLL patients [females: N=75 (39%), males: N=118 (61%)]. At inception of targeted treatment the median age was 65 years (range 32-82), 63 patients (33%) had del(17p), 92 (47%)Binet stage C, 62 (32%) ECOG score >1, 65/166 (39%) IgG level <5 g/L, 79/166 (47%) IgA level <0.8 g/L. Nine patients with del(17p) were treatment naïve, while the rest of the patients were relapsed with the median number of previous therapy lines of 2 (range, 1-12). Five patients started targeted therapy with venetoclax. All other (188) received ibrutinib, in 31 with monoclonal antibodies, in 3 with chemotherapy;in 34 ibrutinib was switched to venetoclax-regimens due to progression. From 1 April 2020 to 31 March 2021, 40 patients have died [Progression15 (37.5%), COVID-1920 (50%), Infection1, Other4 (10%)]. In total, we have identified 110 episodes of bacterial infections and 247 episodes of mixed (undefined) infections other than COVID-19 (n=88). Comparison of the predicted and real frequencies indicated a 3.7-fold reduction in bacterial infections during the lockdown. A weekly plot of infection rates for the entire patient sample is shown in Figure 1. Restrictive measures included reducing the number of clinic visits, prescribing drugs for a longer period, and avoiding the use of monoclonal antibodies. After data normalization, the median number of outpatient visits per month decreased from 271 in the first period to 172 in the second period (p<0.0001). There was a significant correlation between the number of visits and frequency of bacterial and mixed infections (Pearson's correlation coefficient =0.39 and 0.73, 2-month window mean). In the first 6 months of ibrutinib use, infections are more frequent and this could be a confounding factor. To evaluate this hypothesis, patients were divided into four treatment inception cohorts (2015-2016, 2017, 2018, and 2019), then the dynamics of infections before and after lockdown were compared (Figure 2). A trend toward fewer infections after the introduction of restrictive measures was observed in all subgroups;thus, the inception of ibrutinib was not a substantial factor. The structure and frequency of infectious episodes are described in Table 1. Conclusion: A decrease in the incidence of bacterial and mixed infections during the first year of the pandemic was detected, possibly due to SARS-CoV-2 restrictive measures. A positive correlation between in-hospital visits and the incidence of bacterial infections points at the role of hospital- acquired infection and attests to the necessity of reorganizing care for CLL patients. Telemedicine, door delivery of medicines, and in-home collection of biospecimens may enable less frequent hospital visits and a potential decrease in morbidity and mortality due to infections.
ABSTRACT
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.
ABSTRACT
The COVID-19 pandemic has prompted the need to provide enzyme replacement therapy (ERT) for Pompe patients at home. However, this is not allowed in most countries due to safety concerns related to the risk of infusion associated reactions (IARs). We have provided approximately 27,000 alglucosidase alfa (recombinant human alpha-glucosidase, Myozyme) infusions. Here we present data on the safety of home-based infusions of alglucosidase alfa in patients with late-onset Pompe disease (LOPD). Data on patient descriptives, infusion characteristics and IARs from patients starting ERT between 2006 and 2018 were collected and analyzed. IARs were graded with the Common Terminology Criteria for Adverse Events (CTCAE) classification. Data on 16,920 infusions with alglucosidase alfa in 114 LOPD patients were analyzed. 3962 infusions (23.4%) were given in hospital and 12,958 (76.6%) at home. The majority of infusions (88.7%) was administered using a standard infusion schedule. In 78 (2%) of hospital infusions and 132 (1.0%) of home infusions an IAR occurred. Most IARs were mild (73 in hospital;126 at home), only a few moderate IARs (3 in hospital;5 at home) occurred. No severe IARs occurred. Our data demonstrate that few IARs occur during alglucosidase alfa infusions in patients with LOPD. No severe IARs occurred. The majority of IARs at home were mild and did not need additional medical intervention. This demonstrates that alglucosidase alfa can be safely administered in the home situation, provided the appropriate infrastructure is present.