Safety and Immunogenicity of BNT-162b2 versus Chadox1 Vaccine in Solid Organ Transplant Recipients: Prospective Study

Purpose: Data showed seroconversion after different SARS-CoV-2 vaccination platforms might yield diminished response in transplant recipients. However, it is unknown whether different vaccination platforms could offer a specific grade of protection against SARS-CoV-2. Method(s): we prospectively studied adult kidney & liver recipients who received who had no previous COVID-19 infection, and received either ChAdOx1 or BNT- 162b2 vaccines between January 2021 to September 2021, with an assessment of IgM/IgG spike (S) antibodies. Result(s): Our cohort is composed of kidney (n=235) or liver (n=217) patients, who have received either ChAdOx1 (N=157) or BNT-162b2 (n=295). The response was higher with mRNA vaccine. Unresponsiveness is found to be mainly linked to diabetes and older age. Side effects were similar to those reported in clinical trials. Conclusion(s): mRNA vaccines might elicit a higher humoral immunity response as compared with ChAdOx1 in immunosuppressed transplant patients.

Safety and Efficacy of Azacitidine with Venetoclax for Newly Diagnosed Intensive Chemotherapy Ineligible, and Relapsed or Refractory Acute Myeloid Leukemia in Arab Population: A Single-Center, Retrospective Study

Background: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) 75 years or older, or unfit for intensive chemotherapy. As precision therapy in AML expanded with the addition of venetoclax among others in the therapeutic armamentarium of AML, efficacy and safety reports in ethnic minorities are limited, with a background of well recognized inter-ethnic differences in drug response. Phase III data from VIALE-A, as well as VIALE-C, was limited for the Arab population as no site opened in the Arab world. We herein report our experience on the use of venetoclax with azacitidine in patients with newly diagnosed or relapsed/refractory AML in the Arab population. Methods: Retrospective-single center review on the use of Azacitidine with venetoclax in older patients (aged ≥60 years) with newly diagnosed AML, not eligible for intensive chemotherapy;secondary AML and relapsed or refractory AML. All patients self-identified of Arabic ethnicity. Patients who received previous BCL2-inhibitor therapy were excluded. Patients who received at least one dose of treatment (Azacitidine ≥3 days, >14 days of venetoclax) were included in the intention to treat analysis. Patients typically received azacitidine 75 mg/m2 intravenously for 7 days with oral venetoclax 400 mg daily for induction, with appropriate dose adjustment for concomitant use of azoles. This is followed by the same regimen in consolidation, with adjustment according to response and side effects at the treating physician's discretion. The primary endpoint was overall survival. The secondary endpoints include response rate, safety, and relapse-free survival. Results: Between July 2019, and July 2021, we identified 19 patients;13 (68%) had newly diagnosed AML (ND-AML), and 6 (32%) had relapsed or refractory AML (R/R AML). The median age was 70 years (17-82). In the ND-AML, most patients had an adverse ELN 2017 AML (69%) with 23% having either intermediate or adverse AML (Negative for CBF, NPM1, FLT3-ITD and biCEBPA, but missing NGS data for adverse mutations Tp53/ASXL1 and RUNX1). Only one patient was classified as intermediate-risk AML. The overall response rate in the ND-AML was 77%, with 46% achieving complete remission (CR), and 23% CR with incomplete count recovery (CRi) [Table]. One patient achieved PR after the first cycle (blast 7% by morphology and 1.5% by flow cytometry) and did not have a subsequent bone marrow evaluation, however had a full count recovery. Among the responders in the ND-AML cohort, 4 deaths were noted. One death was related to COVID-19 associated pneumonia, one due to graft failure (at day 42 post Haplo-SCT), one due to septic shock, and one was related to relapse disease. The overall survival and relapse-free survival for ND-AML were 5.6 months for both [Figure]. In the R/R AML, 66% had prior HMA exposure, and all patients did receive high-intensity chemotherapy. The median number of prior treatments was 3 (1-5). the response rate was 80% (4/5), with 60% achieving CR. All patients are still alive with a median follow-up of 7.6 months. One patient had progressive disease. One patient is early to evaluate and was not included in the response analysis [Table]. The 30-day mortality was zero in both ND-AML and R/R AML cohorts. Conclusions: In a majority of adverse risk ND-AML, and in heavily pretreated R/R AML, the response rate and overall survival is comparable to what has been previously reported. Our data support the use of this regimen in older patients with newly diagnosed AML, patients with relapsed or refractory disease, and those with adverse-risk features. This analysis is limited by the small number of patients, and by the lack of ELN 2017 favorable-risk AML. Future prospective and randomized studies are needed to clarify activity and safety in the Arab population, as well as in the high-risk AML subset. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Polatuzumab Vedotin As a Salvage Treatment in Relapsed or Refractory DLBCL: Single Center Experience

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for approximately 25% of all newly diagnosed patients (Swerdlow et. al. IARC, 2017). It is estimated that 40% of patients are refractory to, or relapse after treatment with chemo-immunotherapy (R-CHOP). Salvage therapy with autologous stem-cell transplantation (ASCT) can cure around 40% of those patients, nevertheless, the prognosis is poor for most patients with R/R DLBCL who are relapsed after, or ineligible for ASCT, and in those with suboptimal response to salvage chemotherapy. Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate delivering monomethyl auristatin E (MMAE), a microtubule inhibitor. It was granted accelerated approval by the US FDA on June 2019 for treatment of R/R DLBCL after at least two prior therapies, in combination with bendamustine and rituximab. We herein report our experience on the use of polatuzumab in patients with R/R DLBCL. Methods: Retrospective-single center review on the use of polatuzumab vedotin as part of a compassionate program in patients with R/R DLBCL between June 2018 and July 2021. Inclusion criteria for the study were: age ≥ 18 years, R/R DLBCL [both de-novo and transformed lymphoma], 2 or more prior lines of therapy, and treatment with polatuzumab-based therapy for at least 1 cycle. Patients with CNS involvement were excluded. The compassionate use access program provided polatuzumab at a dose of 1.8 mg/kg, administered with or without bendamustine (up to two doses of 90 mg/m2,) and rituximab (375 mg/m2). Treatment was given every 21 days for up to 6 cycles. Results: we identified 3 patients with R/R DLBCL who were treated with polatuzumab-based therapy. The median number of prior therapies was 2 (2 - 5). The median IPI and CNS-IPI score were 2, (1 - 4) and 2, (2 - 5), respectively (Baseline characteristics are summarized in Table). The median number of Pola-BR cycles received was 3 (2 - 6). One patient completed 6 cycles of polatuzumab with bendamustine and rituximab and achieved partial response. The other two patients were taken of treatment at the time of progression on cycles number 1 and 3. Treatment options were limited after polatuzumab-based therapy. The patient who achieved partial response after 6 cycles of Pola-BR maintained that response for 11 months without additional treatment and died due to COVID-19 associated pneumonia. One patient been screened for Glofitamab compassionate use program, and one patient elected to receive no further therapy. Conclusions: Polatuzumab-based treatment in R/R DLBCL is a promising treatment in an otherwise difficult to treat patient population. The compassionate use program provides access in developing countries to an otherwise prohibitively expensive emerging therapeutic armamentarium in R/R DLBCL. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Safety of ambulatory high-dose Methotrexate (HDMTX) administration among hematological malignancies patients in tertiary care center

Background: Methotrexate (MTX) is an antimetabolite, that mainly acts through the inhibition of the enzyme dihydrofolate reductase and the subsequent depletion of intracellular folate stores. High-dose MTX (HDMTX)is defined by the dose of more than 1 g/m2. The utilization of HDMTX is commonly used in solid malignancies such as osteosarcoma and hematological malignancies such as acute lymphoblastic leukemia and non-Hodgkin's Lymphoma. Urine Alkalinization using intravenous sodium bicarbonate and calcium folinate to facilitate clearance of MTX are crucial two steps in MTX clearance and to avoid or minimize side effects such as nephrotoxicity and hepatotoxicity. For that reason, most institutions are requiring patients to be admitted with a minimum length of stay of 72 hours until methotrexate clearance is achieved with a serum level of < 0.1 micromol/L. Aims: Here, we are assessing the safety of ambulatory HDMTX among adult patients. Regular laboratory monitoring, adequate oral hydration and oral medications were utilized to enhance methotrexate clearance without the necessity to use devices at home for infusion or admitting the patient Methods: This trial is open-labeled, single arm study that aims to evaluate the safety of high dose methotrexate administration in an outpatient setting among adult patients with hematological malignancies in a tertiary care center. The study aims to cover a cohort of patients with hematological malignancies from 14 to 60-years-old treated at KFMC scheduled to receive HDMTX from (February-2020) to (February-2021). treatment protocol is showing in figure 1. Results: Twenty-seven (n=27) cycles were done until now. Around 70.37% of the patients were diagnosed with diffuse large B cell lymphoma (DLBCL). Thirteen patients (48.1) % of the patients achieved MTX level less than 0.1 micromol/L by 48 hours and 24 patients (88.8%) achieved the same level by 72 hours. Only three (11.1%) patients did not clear their methotrexate by the end of 72 hours;one patient was admitted due to acute kidney injury, the second was managed as outpatient as that occurred at the mid of COVID- 19 bed crises, and the third one refused admission and was following his labs at the hospital at his hometown. By 72 hours, 29.63% had reversible asymptomatic elevation of creatinine, and all of them were grade one. By 72 hours, around 44.44% had reversible asymptomatic hepatotoxicity, and all of them were grade 1. Among the 27 patients, only one suffered from acute kidney injury that necessitated admission for supportive care, which was totally reversible. The patient was not compliant to the treatment protocol and was excluded for subsequent cycles. Summary/Conclusion: Our preliminary results suggest that ambulatory HDMTX is safe, cost effective, more comfortable for patients. These results encourage the use of this approach more frequently as it decreases hospitalization and thus reduces cost, increases patient satisfaction and helps to solve the issue of bed crisis.

Improvising medical teaching during pandemic through the platform of publishing to convey specific case based learning to undergraduate dental students – Part 1 (psychosocial learning)

The surge of covid 19 pandemic has affected everyone in almost all parts of life. Medical/dental education is no exception. Teaching as well as student learning has been compromised with norms like social distancing, personal protective wear and lockdowns. Reduced school times, absence of group discussions and clinical demonstrations have prompted teachers to convey course information in different ways. The fear of contracting coronavirus and then infecting respective families adds to the always stressed medical students and staff. Prior to covid 19, studies have shown students to be less attentive which leads to their poor retention of case based information taught in the clinical sessions. During the pandemic, theory classes could be managed through online portals, but clinical learning in patients cannot be compensated by such means. With a contextual background of such factors, this two part case series is an attempt to fulfill the void in teaching that has occurred during a pandemic. 87 students (47 female, 40 male) who were enrolled for the course (Clinical Fixed Prosthodontics) (SDS 543 and SDS 544) for academic year December 2020 – June 2021 were asked to submit their clinical cases on a template along with the grades obtained. Cases of fixed partial denture in Kennedy class 3 partial edentulous situation were selected on the basis of complexity in history, clinical examination, diagnosis and prosthesis design. All cases were analysed under two main heading (psychosocial learning, applied basic sciences). In this the first part of the article, multiple selected cases are presented in a four tier series. Major or minor learning skills that students lacked have been highlighted and discussed. Since many students were not able to see each others cases, the authors predict that publishing the cases will achieve two objectives. Firstly, all students will be able to see each others work and what they were taught and secondly, students are expected to take critical evaluation of authors seriously and use this platform as a means to improve those deficiencies.