Isopp 2023

The proceedings contain 109 papers. The topics discussed include: dose intensity of palbociclib and initial body weight dosage: implications on progression free survival in 220 patients with ER+/HER2-negative metastatic breast cancer;characteristics of Nirmatrelvir/Ritonavir (Paxlovid) recipients and clinical interventions by oncology pharmacists at a tertiary outpatient cancer center;safe handling of non-carcinogenic drugs in the Ghent University Hospital: development, implementation and communication of hospital-specific guidelines;case series: use of olaparib in uncommon locations in patients with impaired homologous recombination;real-world data evaluation of medicines used in special situations in oncohematology: a retrospective study from a comprehensive cancer institution;Dostarlimab in the treatment of recurrent endometrial cancer: real life experience;medication-related osteonecrosis of the jaws and CDK4/6 inhibitors in breast cancer;and efficacy and safety outcomes of generic imatinib in adults with chronic myeloid leukemia (CML) following the switch from branded imatinib.

Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection

The current coronavirus disease 2019 (COVID 19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. The full impact of the COVID 19 pandemic, caused by the SARS CoV 2, on the field of hematopoietic cell transplantation (HCT) is unknown. Here, we report a rare case of a 21-year-old male patient known to have chronic myeloid leukemia (CML) with progression to T-cell lymphoblastic lymphoma as extramedullary blast crisis of CML. The patient was treated by pediatric chemotherapy regimen then. He underwent haploidentical stem cell transplantation. Posttransplantation, on day +7, he developed SARS-CoV-2 after receiving stem cell graft from a donor who was diagnosed with SARS-CoV-2 on the day of stem cells harvesting. The case elaborates complications and outcome of a patient receiving stem cell transplant from a donor with SARS-CoV-2 infection.Copyright © 2023 Journal of Applied Hematology Published by Wolters Kluwer - Medknow.

Relative Bioavailability and Food Effect of Asciminib Pediatric Mini-tablet Formulation Compared to the Reference Tablet Formulation in Healthy Adult Participants.

Asciminib, a first-in-class allosteric BCR::ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP) is used in the treatment of chronic myeloid leukemia. We describe a randomized, single-dose, open-label, four-period crossover study in healthy adult participants (N = 24) which evaluated the relative bioavailability of a single 40-mg dose of asciminib in pediatric formulation (1-mg mini-tablets) compared with the reference adult tablet under fasted conditions. Additionally, the effect of food on the bioavailability of the mini-tablet formulation was evaluated. Under fasted conditions, asciminib exposure was similar for both formulations (geometric mean [Gmean ] area under the concentration-time curve from time 0 to infinity [AUCinf ] 5970 and 5700 ng ×h/mL, respectively). Food decreased the AUCinf and maximum plasma concentration (Cmax ) of the asciminib mini-tablets; this effect was more pronounced with a high-fat meal (Gmean ratios [90% confidence interval]: fasted/low-fat meal, 0.42 [0.38-047], 0.32 [0.28-0.37], respectively; fasted/high-fat meal, 0.30 [0.27-0.34], 0.22 [0.19-0.25], respectively). The mini-tablets were assessed to be easy to ingest with good palatability. Asciminib doses for a pivotal pediatric clinical trial will be defined using physiologically based pharmacokinetic modeling, which will consider the age and the higher food effect observed with the mini-tablets.

Incidence of symptomatic Covid-19 infections in patients with mastocytosis and chronic myeloid leukemia: A comparison with the general Austrian population.

BACKGROUND: The SARS-COV-2 (Covid-19) pandemic has impacted the management of patients with hematologic disorders. In some entities, an increased risk for Covid-19 infections was reported, whereas others including chronic myeloid leukemia (CML) had a lower mortality. We have analyzed the prevalence of Covid-19 infections in patients with mastocytosis during the Covid-19 pandemic in comparison to data from CML patients and the general Austrian population. MATERIALS AND METHODS: The prevalence of infections and PCR-proven Covid-19 infections was analyzed in 92 patients with mastocytosis. As controls, we used 113 patients with CML and the expected prevalence of Covid-19 in the general Austrian population. RESULTS: In 25% of the patients with mastocytosis (23/92) signs and symptoms of infection, including fever (n = 11), dry cough (n = 10), sore throat (n = 12), pneumonia (n = 1), and dyspnea (n = 3) were recorded. Two (8.7%) of these symptomatic patients had a PCR-proven Covid-19 infection. Thus, the prevalence of Covid-19 infections in mastocytosis was 2.2%. The number of comorbidities, subtype of mastocytosis, regular exercise, smoking habits, age, or duration of disease at the time of interview did not differ significantly between patients with and without Covid-19 infections. In the CML cohort, 23.9% (27/113) of patients reported signs and symptoms of infection (fever, n = 8; dry cough, n = 17; sore throat, n = 11; dyspnea, n = 5). Six (22.2%) of the symptomatic patients had a PCR-proven Covid-19 infection. The prevalence of Covid-19 in all CML patients was 5.3%. The observed number of Covid-19 infections neither in mastocytosis nor in CML patients differed significantly from the expected number of Covid-19 infections in the Austrian population. CONCLUSIONS: Our data show no significant difference in the prevalence of Covid-19 infections among patients with mastocytosis, CML, and the general Austrian population and thus, in mastocytosis, the risk of a Covid-19 infection was not increased compared to the general population.

Co-occurrence of CML Blast Crisis and Severe COVID 19 Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affecting multiple organ systems. It can cause severe cytokine storms leading to intensive care unit admission requiring mechanical ventilation. However, there have been few studies establishing the outcomes of chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors who are infected with COVID-19. We present a 69-year-old male with a history of CML on imatinib therapy with COVID-19 who developed acute respiratory distress syndrome needing mechanical ventilatory support, shock requiring vasopressors, and worse outcome secondary to blast crisis.

Spontaneous rectus sheath hematoma in a patient with COVID-19 and chronic myeloid leukemia. A case report and literature review.

Introduction: Rectus sheath hematoma is a rare entity. This report presents a clinical case of a rectus sheath hematoma in a patient with COVID-19 pneumonia and chronic myeloid leukemia, along with a review of the literature. Case Report: A 55-year-old male patient, hospitalized for COVID-19 pneumonia and chronic myeloid leukemia, presents with tachycardia and hypotension. Computed tomography shows a rectus sheath hematoma. Surgical management was performed to control bleeding and drainage of the hematoma. There were no postoperative complications or need for reoperation. Discussion(s): Hemorrhagic complications in patients with COVID-19 are seldomly reported. Bleeding is a possible complication in patients with chronic myeloid leukemia. It is important to take into account rectus sheath hematoma in patients with COVID-19 and/or chronic myeloid leukemia who present with abdominal pain, for early management by a multidisciplinary team. Conclusion(s): Active surveillance and a high index of suspicion are key to identifying potential bleeding complications in patients with COVID-19 and/or chronic myeloid leukemia.Copyright © 2023, Sociedad de Cirujanos de Chile. All rights reserved.

Giant Cellulitis-Like Sweet Syndrome Masquerading As Cellulitis and Shingles: A Case Report and Literature Review.

Sweet syndrome (SS) is also known as acute febrile neutrophilic dermatoses. Clinically, SS features fever, arthralgias, and the sudden onset of an erythematous rash. The morphologies of skin lesions in SS are heterogenous, varying from papules, plaques, and nodules to hemorrhagic bullae, which sometimes makes the diagnosis of SS more challenging. We report a 62-year-old obese male with a history of chronic myeloid leukemia in remission for 10 years who presented with a rash for five days. The patient reported prodromal flu-like symptoms with subjective fever, malaise, cough, and nasal congestion followed by a sudden onset, painful, non-pruritic rash. The rash was associated with bilateral hip arthralgias and abdominal pain. The patient denied any recent travel, exposure to sick contacts, or the use of any new medications. Physical examination showed a well-demarcated, non-blanching, confluent, erythematous plaque involving the bilateral buttocks and extending to the lower back and flanks with coalescent "juicy"-appearing plaques and flaccid bullae. No oral or mucosal involvement was noted. Laboratory investigations revealed mild leukocytosis, elevated inflammatory markers, and acute kidney injury. The patient was started on antibiotics given the cellulitis-like skin lesions, leukocytosis with neutrophilia, and elevated inflammatory markers. Dermatology was consulted, who attributed the patient's rash to shingles and recommended initiating acyclovir and obtaining a skin biopsy. However, the patient's rash and arthralgias worsened with anti-viral treatment while awaiting pathology results. Antinuclear antibodies, complement, human immunodeficiency virus, hepatitis panel, blood cultures, and tumor markers were all negative. Flow cytometry showed no evidence of hematopoietic neoplasms. The skin punch biopsy revealed dense neutrophilic infiltration in the dermis with no evidence of leukocytoclastic vasculitis, consistent with acute neutrophilic dermatoses. The diagnosis of giant cellulitis-like Sweet syndrome was established, and the patient was started on prednisone 60 milligrams daily. His symptoms improved promptly with steroid treatment. Our case suggests that SS can camouflage a wide spectrum of diseases, including cellulitis, shingles, vasculitis, drug eruptions, leukemia cutis, and sarcoidosis, which emphasizes the importance of keeping a high index of suspicion for SS when assessing the clinical constellations of fever, neutrophilia, and erythematous plaques suggesting atypical cellulitis. Approximately 21% of Sweet syndrome is associated with malignancy. Sweet syndrome can precede, concur with, or follow the onset of malignancy. Due to the lack of a systematic approach to patients with SS, under-investigation and diagnostic delays are common. Therefore, further screening and continuous monitoring in patients with SS becomes especially important in facilitating the early detection of a potential underlying malignancy and assists in initiating adequate therapy.

Single-center study on SARS-CoV-2 infection in patients affected by CML: Vaccination status and bosutinib therapy as possible protective factors for hospitalization.

INTRODUCTION: COVID-19 pandemic had a considerable impact among haematological patients. On the other hand, the effect of this disease on patients (pts) affected by Chronic Myeloid Leukemia (CML) is not clearly defined. OBJECTIVES: The primary objective of this study was to evaluate mortality-hospitalization rates and possible protective factors for hospitalization in CML pts affected by COVID. METHODS: We collected data from CML patients followed at our institution whotested positive for SARS-CoV-2 infection. The following variables were assessed: demographical data, type of TKI therapy, vaccination status, presence of cardiovascular disease (CVD), period of infection, COVID-19 presenting symptoms, severity and mortality. Data were collected retrospectively and then analysed in univariate and multivariate analysis. RESULTS: Out of a total of 325 CML pts treated at our institution, we recorded 72 SARS-CoV-2pts (22%) who tested positive with a SARS-CoV-2 PCR assay. Twenty two were infected in 2020 (30%), 16 patients in 2021 (22%) and 34 in 2022 (46%); with a hospitalization rate of 27%, 25% and 3% respectively. Of the 72 confirmed infections, 13 pts (18%; (CI) 10-28) were asymptomatic and 48 (66%; CI: 55-76) had mild symptoms. A total of 11 pts were admitted to hospital and 3 of these required ICU admission. No deaths were recorded. The probability of hospitalization was significantly reduced if patients were vaccinated (odds ratio OR 0.037 with CI: 0-0.33 p 0.002) or treated with Bosutinib (OR 0.06 with CI: 0-0.5 p 0.008). CONCLUSION: In the present study, no significant increase in mortality was noted among patients with CML as compared to the general population inItaly. Vaccination and treatment with bosutinib were identified as baseline characteristics that were associated with a decreased risk of hospitalitazion resulting from COVID-19 infection.

Postmarketing data collection and evidence evaluation

AIFA Monitoring Registries (wMRs) constitute a collection of drug registries (product registries) deployed to physicians and pharmacists through a national web platform. They have been adopted in the clinical practice since 2005 and are used to define the population for which the drug is available under the umbrella of the National Health Service (NHS - Servizio Sanitario Nazionale SSN), monitor prescription appropriateness and ensure the rapid access to potentially priority medicines allowing the implementation of patient-based managed entry agreements (MEAs). Each registry consists of specific data entry forms, collecting data at the patient level and filled in by authorized clinicians and pharmacists. The required information includes: 1. Registration form with patient personal data (anonymized after registration);2. Eligibility and clinical data form;3. Prescription and administration forms;4. Evaluation of disease status and treatment update form;and 5. End-of-treatment form. Evaluation and end-of-treatment forms provide main safety and effectiveness data at a patient level. Moreover, since entry forms are the same throughout the nation, this platform allows access to treatment in a homogeneous manner throughout the country. Recently, a new type of registry has been released, with the primary aim of monitoring the pregnancy prevention programme (PPP) following the prescription of potentially teratogenic medicinal products. All this information is collected in a national database that represents a key source of postmarketing evidence that is frequently exploited to answer both administrative and clinical questions, such as drug utilization among a specific pharmacological class or the effectiveness of a drug in a census consisting of all Italian patients treated with that medicinal product. For example, given the prospective nature of the data contained inside the wMRs, AIFA together with members of the relevant scientific associations were able to evaluate the effect of the COVID- 19 pandemic and lockdown measures on the new prescription (i.e. first prescription) of some cardiovascular drugs in Italy and suggest new studies to analyse the occurrence of new cardiovascular- related events resulting from the decline in the activation of these treatments. Equally important is the work assessing the effectiveness of tyrosine kinase inhibitors in chronic myeloid leukaemia (CML) patients in Italian clinical practice, which was able to highlight important aspects on both expected mortality and consequential use in first and second line TKIs in Italy. Finally, the wMRs were also a critical instrument in the management of the COVID-19 medicinal products since 29 October 2020, providing essential evidence on drug availability through the country, predicting possible shortages and publishing hundreds of freely available reports on the utilization trend of COVID-19 drugs in the different Italian Regions. In conclusion, the wMRs represent a key tool to generate pharmaco-epidemiological evidences in the Real-world setting and monitoring drug appropriateness for expensive, innovative drug.

5th ECOP, European Conference of Oncology Pharmacy

The proceedings contain 130 papers. The topics discussed include: frequency of measuring body weight in (sub)populations of patients with cancer treated with chemotherapy;simple approach to enhance green tea epigallocatechin gallate stability in aqueous solutions and it bioavailability: experimental and theoretical approaches;incidence of cisplatin-induced nephrotoxicity and associated risk factors: single-center experience;impact of the 2019 coronavirus pandemic on cancer treatment in the Calabria Region, Italy;Palbociclib associated neutropenia in clinical practice;successful introduction of a point mutation into the genome of a primary colon cancer cell line using CRISPR base editing technology;incidence of cisplatin-induced nephrotoxicity and associated risk factors: single-center experience;real world data of alk-inhibitors in patients with advanced or metastic non-small cell lung cancer;pembrolizumab in non-small-cell lung cancer: a systematic review of real life data in Spain;gynecomastia in a male after imatinib treatment for chronic myeloid leukemia;and results after discontinuation of pembrolizumab in metastatic melanoma or lung cancer patients: real-word experience.

CML Outcomes and Care Delivery During the COVID-19 Pandemic in Low- and Middle-Income Countries.

PURPOSE OF REVIEW: The study aims to evaluate the impact of COVID-19 on the delivery of health care and services to patients with chronic myeloid leukemia in low- and middle-income countries (LMICs) accessing treatment through The Max Foundation. RECENT FINDINGS: An online survey was developed and sent via email to 527 partner physicians who had active patients under their care in July 2020, asking about the disruption of health services with multiple-choice answers or a five-point ordinal scale. Data from The Max Foundation's Patient Access Tracking System (PATS®) was analyzed to evaluate program performance in 2020 compared with 2019. PATS® is used to track key patient information and supply chain data to ensure robust reporting, quality assurance, and safety. Among the 111 physicians who responded (20% response rate), 48% reported that someone on their team had contracted COVID-19. A total of 95 (85%) physicians reported at least some disruption of services to patients due to COVID-19, with 29 (26%) reporting frequent or complete disruption. Almost all physicians in the South Asia and Asia Pacific regions reported disruption (96% and 95%, respectively), compared with three quarters of physicians in Latin America. Institutions overcame challenges using a variety of solutions including telemedicine (60%), electronic prescriptions (45%), home delivery via courier services (31%), government workers (9%), and dispensation coordination with regional hospitals (14%). The COVID-19 pandemic has disrupted services for CML physicians and patients worldwide. Overall, these disruptions did not appear to significantly affect The Max Foundation's ability to provide patients with access to treatment, as novel approaches in telemedicine, supply chain, and dispensing, as well as provision of guidance and support for physicians were utilized to overcame disruption of services.

Treatment- Free Remission in Chronic Myeloid Leukemia -Experience of a Single Brazilian Private Institution Using Imatinib Copie

Introduction: Evidence of several studies suggest that patients who have achieved a sustained stable deep molecular response (DMR) as MR4 and MR4.5 can be safely discontinued with close monitoring without relapse, despite BCR/ABL1 DNA remaining detectable. In Brazil, CML patients have received almost exclusively Imatinib as first-line treatment. However, in both scenarios there is a limit coverage of PCR exams/ year which allows for adequate monitoring but it is not sufficient for the implementation of TFR safely in eligible patients. Aim(s): To report a Brazilian single institution Imatinib discontinuation trial and to evaluate factors impacting treatment -free response (TFR) and treatment free survival (TFS) provided by own founds. Method(s): From 2020 -2021, 26 eligible patients were invited to participate in a single arm trial of Imatinib discontinuation (DIP). Inclusion criteria: age > 18 years, chronic phase, minimum of 04 years of Imatinib therapy, deep molecular response sustained > or = 02 years (confirmed by 04 tests in the last two years, defined MR4.0 or MR 4.5 and a confirmatory exam at the moment of the screening). Atypical transcripts were excluded. After discontinuation, patients were monitored by RT- PCR monthly in the first year, every two months in the second year and every three months since the third year. Criteria for Imatinib re-initiation: loss of MMR confirmed by two exams, loss of cytogenetic response, loss of hematologic response, disease progression. TFR was calculated from the date of discontinuation until first event: loss of MMR, Imatinib reintroduction, death any cause or last follow up. TFS was calculated from the date of imatinib discontinuation until reintroduction or last follow- up (censoring deaths not related to CML). The costs of exams were provided by own founds of our institution. Result(s): From 26 patients, 20 patients agreed to consent inform to discontinuation of imatinib. 06 patients declined despite information because their insecurity about TFR. Twelve patients (60%) presented MR4. Median age was 52.3 years old and 13 (65%) were female. Median time diagnosis to discontinuation of imatinib 8.04(4.6-15.5) years. Twelve (60%) patients sustained TFR. Seven patients of twelve had presented MR 4 and five had MR 4.5 in the screening, respectively. (p = 0,85). It means 58,3% of the total of patients with MR 4 and 62,5% with MR 4.5. In this interim analysis the median time of follow up was 14.5 (2.7-18.8) months. One patient died due to COVID19 with major molecular response (MMR). Eight (40%) lost MMR and imatinib was restarted. In this group the median time until MMR loss was 7.24 (2.1-13.8) months. At this moment, 07 patients (87,5 %) recovered MMR. In addition, in this group 06 patients (75%) achieved the same level of MR with reintroduction of imatinib with median 5.2 (3.7-6.3) months. Regarding adherence, 4 (20%) had some absences in monthly medical consultations and 1(5%) missed follow-up. Fifteen tests (6.14%) were performed to confirm MR loss, however only in 8 tests (53.3%) were confirmed. In fact, 04 patients (33,33%) still in TFR because of the double confirmatory test. There was no transformation to advanced phases. Gender, age at de diagnosis, age at discontinuation, Sokal, BCR-ABL trasncripts type, duration of Imatinib therapy, duration of MR 4.0 or MR4.5 did not affect TFR. Withdrawal syndrome occurred in 05 patients (25%);04 patients with grade 1 and 01 patient with grade 2, had been used corticosteroid for few days. Conclusion(s): The preliminary results of this trial demonstrated the feasibility and safety of Imatinib discontinuation, even using Brazilian copies, and the results were similar of that presented in another trials. Copyright © 2022

COVID-19 infection in patients with chronic myeloid leukemia in the Orenburg region during the SARS-CoV-2 pandemic

Background. Oncohematological patients are more predispose to SARS-CoV-2 infection than healthy individuals and patients with malignant neoplasms, and also they have a worse prognosis, which is because of immune system disorders, both due to the underlying disease and as a result of immunosuppressive therapy. There is limited data regarding the impact of SARS-CoV-2 infection on the survival of patients with chronic myeloid leukemia (CML). Aim. To evaluate the course and outcome of COVID-19 in patients with CML in the Orenburg region during the SARS-CoV-2 pandemic. Materials and methods. All 166 patients with CML over 18 years of age were analyzed during the COVID-19 pandemic between february 2020 and December 2021. The source of information was data from the personalized register of patients with CML and the unified state health information system. Results. The proportion of SARS-CoV-2 infection among patients with CML was 36 %. The risk of infection was not affected by age, gender, work features, place of residence, phase or duration of the disease, and therapy. underwent COVID-19 patients were 1.6 times more likely to be overweight and 2 times more likely to have a second cancer. A significant increase in the number of outpatient visits to polyclinics and number of hospital admissions during the pandemic was revealed in the group of patients who had SARS-CoV-2 infection. underwent COVID-19 patients were over 60 years of age in 48.3 % of cases and had one or more comorbidities in 77.6 % cases. SARS-CoV-2-infected patients with CML had a favorable outcome: a mild course of infection in 75.9 % of cases and a low mortality rate - 6.8 % (4 of 58 patients) were observed. COVID-19 was recognized as the cause of death in only 2 patients with optimal molecular response and comorbidity. In two other patients who underwent COVID-19, the progression of CML to a blast crisis was recognized as the cause of death. There were no significant differences in mortality level in the group of patients who had SARS-CoV-2 infection and those who did not have COVID-19. Conclusion. patients with CML living in the Orenburg region have a low susceptibility to SARS-CoV-2 infection and a mild course of the disease. The mortality rate for CML patients infected with SARS-CoV-2 was 6.8 %. unfavorable factors in the overall survival of patients with CML infected with SARS-CoV-2 were high comorbidity and blast crisis. Reducing the number of outpatient visits during the pandemic and using remote medical consultations is likely to reduce the risk of SARS-CoV-2 infection. Copyright © 2022 ABV-Press Publishing House. All rights reserved.

COVID-19 Impact on Chronic Myeloid Leukemia Patients.

(1) Background: Chronic myeloid leukemia (CML) is a blood dyscrasia that accounts for about 20% of all leukemia cases. Tyrosine kinase inhibitors (TKIs) are used as first line treatment of CML. The 2019 SARS-CoV-2 outbreak raised new concerns for CML patients, such as whether CML increases the risk of contracting COVID-19, whether TKIs increase that risk, whether these drugs are safe to use during the infection, and whether any other hematologic parameters influence infection outcomes. (2) Methods: In our study we addressed these intriguing questions by using a retrospective analysis of 51 CML patients treated at the Ion Chiricuta Cancer Center, Cluj-Napoca, Romania. Furthermore, we investigated the effects of currently approved COVID-19 vaccines in our CML patients treated with tyrosine kinase inhibitors. (3) Results: Our results have shown that hemoglobin level upon diagnosis of CML has been the only hematologic parameter correlated to the risk of contracting COVID-19 in our CML patients. (4) Conclusions: TKI treatment did not negatively influence COVID-19 risk or the response to the vaccine in our patients. The safety profile of the currently approved COVID-19 vaccines was similar to that of the general population.

Non-Myelofibrosis Chronic Myeloproliferative Neoplasm Patients Show Better Seroconversion Rates after SARS-CoV-2 Vaccination Compared to Other Hematologic Diseases: A Multicentric Prospective Study of KroHem.

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin's lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.

Impact of the COVID-19 pandemic on the regular follow-up and outcomes of patients with chronic myeloid leukemia in chronic-phase.

Introduction: COVID-19 immediately became a major consideration in the management of chronic myeloid leukemia (CML). The influence of such considerations on viral transmission rates and leukemic control remain to be explored. We conducted this study to identify these alterations and to investigate their clinical consequences. Methods: This was a cross-sectional study, performed at a single institution on CML patients who were interviewed with a survey. We compared variables concerning new attitudes in the pandemic era between the 12-month periods before and after the pandemic onset. Outcome data were attained from the hospital archives. Findings: The number of patients receiving regular outpatient care for CML in chronic phase was 210, 91% had achieved at least major molecular responses. We assessed survival, progression, number of clinical visits of all, performed the survey on 89% and evaluated molecular responses on 86.6% of these patients. The frequency of clinical and molecular monitoring was significantly reduced during the pandemic deviating significantly from the guidelines. Frequency of death, progression, loss of molecular response was not significantly increased during the pandemic era despite a few cases where the delay in assessment possibly played a role in the unfavorable outcomes. There were no COVID related deaths or disabilities. Conclusion: The case-based untoward events would have probably been better managed with a more efficient communication web between patients, hematologists, and the laboratory. Therefore, it seems reasonable to consider whether such communicative paths are functional before giving up on the set schedule of CML management at times of uncertainty.

Immunological Response to SARS-CoV-2 After Infection and/or Vaccination Among Chronic Myeloid Leukemia Patients - A Prospective Study

Context: Patients with hematologic malignancies have an increased risk of SARS-CoV-2 infection, severe COVID-19, and higher mortality rates. Objective(s): We investigated the immunological response to SARS-CoV-2 after infection and/or vaccination and explored the impact of treatment response on antibody levels. Design(s): We added a cohort of CML patients to the ongoing study SPARTA. We collected saliva and peripheral blood to measure levels of SARS-CoV-2 antigen and antibodies. Result(s): From 10-1-2021 to 3-31-2022, we prospectively enrolled 69 participants (32 with CML, 37 non-cancer) with similar sociodemographic characteristics. There was a significant difference in the frequency of previous SARS-CoV-2 infections, where the control group had a higher percentage of patients previously diagnosed with COVID-19 (18.8% vs. 84%). Nevertheless, there was no difference in the detection of SARS-CoV-2 at the time of enrollment (0% vs. 5.6%). SARS-CoV-2 antibodies, either IgG or neutralizing (nAB), were detected in most of the participants regardless of cancer status (IgG, 84.4% in the CML cohort and 91.7% in the non-cancer cohort;nAB, 84.4% vs. 88.9%). The two groups had comparable IgG (mean 160.8 vs. 157.5 Ru/mL) and nAB (mean 1,473 vs. 1,509 ng/ml) levels. Overall, IgG and nAB levels were significantly higher in subjects who received the last vaccine dose within 6 months compared to those who received it >=6 months previously (IgG, CML, mean 177.7 vs. 113.2, control 190.5 vs. 134.4;nAB, CML 1,784 vs. 951.9, control 2,066 vs. 1,335). Both groups had comparable mean antibody levels according to the time since the last dose (IgG, <=6 months, 177.7 vs. 190.5, >=6 months, 113.2 vs. 134.4;nAB, <=6 months, 1,784 vs. 2,066, >=6 months 951.9 vs. 1,335). There was no difference in the detection and levels of antibodies according to therapy with TKIs (IgG, mean 158.8 vs. 185.2;nAB, 1,515 vs. 1,883) or achieving MMR (IgG, mean 152.4 vs. 177.5;nAB, 1,447 vs. 1,686). Conclusion(s): The immunological response to SARS-CoV-2 among CML patients is comparable to that in non-CML subjects. TKI therapy and the response to treatment did not impact the development of antibodies. Moreover, antibody levels decreased over time, with the most significant drop after 6 months since the last immunization dose. Copyright © 2022 Elsevier Inc.

CHRONIC EMPYEMA MANAGED WITH TUBE THORACOSTOMY

SESSION TITLE: Problems in the Pleura Case Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Hematologic malignancies can often be complicated by pleural effusion due to leukemic infiltration of the pleura (1). Long term management of resulting chronic plural effusion can be complicated when there is evidence of trapped lung. Subsequent infection may lead to development of chronic empyema which can be difficult to manage in chronically ill patients (2). CASE PRESENTATION: A 65-year-old male with history of chronic myeloid leukemia status post stem cell transplant was admitted with dyspnea and cough. Computed tomography (CT) chest imaging revealed increased volume loss on the left with new air fluid level in a chronic left pleural effusion. (Image 1) Patient's history was significant for chronic left pleural effusion, which was first identified in 2015 and found to be a malignant effusion with evidence of leukemia involvement. Repeat imaging in 2018 (Image 2) revealed continued chronic pleural effusion. Patient was admitted in August 2021 with COVID-19 pneumonia and CT Chest showed chronic loculated left sided pleural effusion. Patient elected to continue to monitor the chronic effusion, which was completed as outpatient every 4 to 6 weeks (Image 3). He remained clinically stable until the presentation to a hospital in January 2022. The chronic empyema was initially managed with tube thoracostomy, intrapleural fibrinolytics and antibiotics. Cultures were significant for Moraxella catarrhalis and Streptococcus pneumoniae. He was determined to be a poor surgical candidate for decortication and treatment with empyema tube was initiated. The empyema tube was incrementally withdrawn as an outpatient and subsequently removed with good clinical recovery. DISCUSSION: Chronic empyema is characterized by thickened parietal and visceral pleura which limits the ability of the lung to re-expand. Surgical management with decortication is the definitive management, however, in poor surgical candidates, management becomes more complicated. Open pleural drainage with an open pleural window can be considered. An alternative option converts tube thoracostomy to open pleural drainage, as was utilized in this patient (2). While comparison of surgical vs non-surgical management of empyema suggests similar mortality (3), non-surgical management of chronic empyema needs more investigation to determine the optimal treatment modality. CONCLUSIONS: Empyema remains a difficult condition to manage. Treatment modalities of chronic empyema are limited in those patients who remain poor surgical candidates. Reference #1: Faiz SA, Sahay S, Jimenez CA. Pleural effusions in acute and chronic leukemia and myelodysplastic syndrome. Curr Opin Pulm Med. 2014 Jul;20(4):340-6. Reference #2: Biswas A, Jantz MA, Penley AM, Mehta HJ. Management of chronic empyema with unexpandable lung in poor surgical risk patients using an empyema tube. Lung India. 2016;33(3):267-271. Reference #3: Redden MD, Chin TY, van Driel ML. Surgical versus non-surgical management for pleural empyema. Cochrane Database Syst Rev. 2017;3(3):CD010651. Published 2017 Mar 17. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff no disclosure on file for Ravi Nayak;

Asciminib (Scemblix): A third-line treatment option for chronic myeloid leukemia in chronic phase with or without T315I mutation.

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of asciminib, an oral tyrosine kinase inhibitor (TKI) used as a third-line treatment option for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase. SUMMARY: CML is a rare cancer caused by a chromosomal translocation that forms a fusion of the BCR and ABL1 genes on chromosomes 22 and 9. Until recently, patients for whom first-line treatment options failed were treated with TKIs that bind to the adenosine triphosphate-binding site on BCR-ABL1. However, because of similar mechanisms of action, there continues to be an unmet need in patients for whom at least 2 TKIs have failed or those with a T315I mutation unable to tolerate ponatinib. In October 2021, the Food and Drug Administration approved asciminib (Scemblix), the first TKI specifically targeting the ABL1 myristoyl pocket (STAMP) via allosteric binding, as a third-line option for patients with chronic-phase (CP)-CML. Asciminib received accelerated approval due to meeting its primary endpoint at week 24, demonstrating a major molecular response rate of 25.5% for patients on asciminib compared to 13.2% for those receiving bosutinib. In addition, patients on asciminib achieved a higher rate of complete cytogenetic response at 40.8% compared to a rate of 24.2% for bosutinib. Clinicians prescribing asciminib should monitor for increased levels of pancreatic enzymes, hypertension, cardiovascular toxicity including ischemic and thromboembolic conditions, and decreased numbers of neutrophils and platelets, as these may require treatment interruption, dose reduction, or treatment discontinuation. CONCLUSION: Asciminib is a unique targeted TKI that provides clinicians with an additional third-line and beyond treatment option for adults with CP-CML regardless of mutation status as well as a second TKI treatment option for patients harboring a T315I mutation.