Immunogenicity and clinical effectiveness of mRNA vaccine booster against SARS-CoV-2 Omicron in patients with haematological malignancies: A national prospective cohort study.

Information regarding the protective anti-SARS-CoV-2 antibody levels and the effectiveness of the mRNA vaccines against the Omicron variant in patients with haematological malignancies is limited. We prospectively followed two times BNT162b2 vaccinated oncohaematological patients (n = 1010) without prior COVID-19 for PCR-confirmed breakthrough infections during the Alpha/Delta and the Omicron phases of the pandemic. Anti-S1-IgG levels were longitudinally monitored in patients who had received the third (booster) vaccine dose. Patients with anti-S1-IgG levels <50 BAU/mL 1 month after the booster had a higher risk of Omicron infections (RR 1.91; 95% CI 1.39-2.63; p = 0.0001) and severe infections (RR 8.74; 95% CI 3.99-19.1; p < 0.0001). Conversely, the risk of severe COVID-19 was <1% with anti-S1-IgG levels >500 BAU/mL and neutralizing antibody concentrations >50 U/mL. The risks of breakthrough Omicron infections (HR 0.55; 95% CI 0.32-0.96; p = 0.034) and severe COVID-19 (HR 0.27; 95% 0.11-0.7; p = 0.0074) were lower among patients who had received the booster dose. In conclusion, low antibody levels are associated with significantly increased risk of both the breakthrough Omicron infections and severe COVID-19. The third mRNA vaccine dose improved the protection against the Omicron and reduced the risk of severe disease.

Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study.

BACKGROUND: Haematological malignancies and their treatments are likely to affect SARS-CoV-2 vaccine efficacy. We aimed to evaluate serological response to BNT162b2 vaccine in patients with haematological malignancies by type of treatment. METHODS: Our national prospective cohort study was done in Lithuania and assessed serological response to one and two BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine doses in healthy health-care workers and in patients with haematological malignancies. Eligible participants were aged 18 years or older, had received both vaccine doses, and had available biobanked blood samples from before vaccination and after the second dose. Biobanked samples and health data were obtained from Vilnius University Hospital Santaros Klinikos Biobank. Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG antibody) concentrations 0-10 days before the first BNT162b2 vaccine, on the day of second immunisation (around day 21), and 7 to 21 days after the second immunisation. Adverse events were assessed by a standardised questionnaire. Breakthrough infections were characterised clinically and by SARS-CoV-2 genotyping whenever possible. This study is registered with ClinicalTrials.gov, NCT04871165. FINDINGS: Between Jan 8 and April 21, 2021, 885 participants with haematological malignancies were included in the study. 857 patients were anti-S1 IgG seronegative at timepoint 0 and constituted the main analysis cohort. The age-matched comparison was made between 315 patients with haematological malignancies who were aged 18-60 years and 67 healthy health-care workers in the same age group. Patients aged 18-60 years with haematological malignancies had lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses than did health-care workers of the same age group (median 6961 AU/mL [IQR 1292-20 672] vs 21 395 AU/mL [14 831-33 553]; p<0·0001). Compared with untreated patients with haematological malignancies (n=53; median 5761 AU/mL [629-16 141]), patients actively treated with Bruton tyrosine kinase inhibitors (BTKIs; n=44; 0 AU/mL [0-7]; p<0·0001), ruxolitinib (n=16; 10 AU/mL [0-45]; p<0·0001), venetoclax (n=10; 4 AU/mL [0-1218]; p=0·0005), or anti-CD20 antibody therapy (n=87; 17 AU/mL [1-2319]; p<0·0001) showed particularly poor anti-S1 IgG antibody responses following two BNT162b2 doses. Patients being treated with tyrosine kinase inhibitors (n=41; 10 537 AU/mL [IQR 2335-19 388]) or patients who received autologous haematopoietic stem-cell transplantation (HSCT; n=192; 6203 AU/mL [1451-16 834]) or allogeneic HSCT (n=122; 6304 AU/mL [1120-16 913]) were among the subgroups with the highest numerical responses. Nine SARS-CoV-2 infections and three COVID-19 deaths were observed among fully vaccinated patients with haematological malignancies. INTERPRETATION: Patients with haematological malignancies mount blunted and heterogeneous antibody responses to the full course of BNT162b2 mRNA vaccination. Patients who are actively treated with BTKIs, ruxolitinib, venetoclax, or anti-CD20 antibody therapies seem to be the most negatively affected and might be left unprotected from SARS-CoV-2 infection. Breakthrough severe SARS-CoV-2 infections in fully vaccinated patients with haematological malignancies emphasise the importance of ongoing strict adherence to non-pharmacological interventions and household vaccination while SARS-CoV-2 is circulating in the community. FUNDING: Vilnius University Hospital Santaros Klinikos. TRANSLATION: For the Lithuanian translation of the abstract see Supplementary Materials section.

Venetoclax-based salvage therapy followed by Venetoclax and DLI maintenance vs. FLAG-Ida for relapsed or refractory acute myeloid leukemia after allogeneic stem cell transplantation.

We retrospectively compared the outcomes of 20 patients receiving Venetoclax + low-dose Cytarabine + Actinomycin D (ACTIVE) with 29 patients receiving FLAG-Ida as salvage therapy for relapsed or refractory AML (R/R AML) after alloSCT. The groups were statistically balanced according to age, performance status, cytogenetics, and previous treatment. The overall response rate (CR + CRp + MLFS) of ACTIVE was 75% (15/20) in comparison to 66% (19/29) in the FLAG-Ida group (p = 0.542). The cumulative CR + CRp rate was significantly higher in the ACTIVE group compared to FLAG-Ida (70% (14/20) vs. 34% (10/29), respectively, p = 0.02). All three patients failing previous Venetoclax therapy and five out of seven patients with previous FLAG-Ida exposure achieved a CR/CRp after ACTIVE induction. ACTIVE patients survived longer compared to FLAG-Ida patients (13.1 vs. 5.1 months, respectively, p = 0.032). The treatment-related mortality was 0% in the ACTIVE group and 34% (10/29) in the FLAG-Ida patients (p = 0.003). The cumulative incidence of relapse did not differ between the two treatment groups. ACTIVE appears to have comparable antileukemic activity and lower toxicity compared to FLAG-Ida resulting in improved survival. Patients with Venetoclax or FLAG-Ida exposure responded to ACTIVE.

Glasdegib in combination with low-dose Cytarabine for the outpatient treatment of relapsed or refractory acute myeloid leukemia in unfit patients.

We retrospectively collected clinical data on 31 relapsed or refractory acute myeloid leukemia (R/R AML) patients who were treated with outpatient glasdegib and low-dose Cytarabine (LDAraC) at our institution. The median age was 67 years (45-86). The median Eastern Cooperative Oncology Group performance status was 2 (1-3). The patients had previously received a median number of 2 (1-4) treatment lines, 61% (19/31) had been treated with intensive chemotherapy, 29% (9/31) had relapsed after allogeneic stem cell transplantation, and 45% (14/31) had had venetoclax exposure. Adverse cytogenetics were identified in 45% (14/31) of the cases. The CR + CRp rate was 21% (6/29) among evaluable patients. The median overall survival was 3.9 months for all patients. Different median overall survival times were observed in responders, patients achieving stable disease and those diagnosed with progressive disease: not reached vs 3.9 months vs 0.8 months, respectively (p < 0.001). The most common adverse events were pneumonia (29%, 9/31), sepsis (23%, 7/31), and febrile neutropenia (16%, 5/31). Glasdegib + LDAraC is a fairly safe, non-intensive, outpatient regimen inducing complete remission and resulting in prolonged survival in some R/R AML patients.

Outcomes of relapsed or refractory acute myeloid leukemia patients failing venetoclax-based salvage therapies.

OBJECTIVES AND METHODS: We conducted a retrospective analysis to evaluate the outcomes of 28 heavily pretreated (median 3 (2-6) treatment lines, sixteen (57%) allotransplanted) relapsed/refractory acute myeloid leukemia patients who had failed salvage venetoclax-based therapies. RESULTS: The median age was 59 years (20-80), 20 patients (71%) had ECOG 2-4 status, and 18 patients (64%) were stratified to European Leukemia Network 2017 adverse risk group. The most common mutations were ASXL1 (21%), RUNX1 (18%), FLT3 ITD/TKD (18%), PTPN11 (15%), NRAS/KRAS (15%), and WT1 (15%). Twenty-two patients (79%) received different post-venetoclax salvage therapies with the overall response rate of 23% (complete remission + morphological leukemia-free state). Three of six (50%) patients achieved complete remissions after therapy with venetoclax + actinomycin D ± low-dose cytarabine. The remaining 6 patients did not receive any further salvage treatment mainly due to poor general condition. The median overall survival was 3.9 months for all patients (4.3 for those receiving post-venetoclax salvage vs 1.3 months receiving palliative care alone, P < .001). CONCLUSIONS: Though the remission rate and survival of patients failing venetoclax are poor, a small proportion of these R/R AML patients may still respond to cautious intensification of chemotherapy with venetoclax.

Mitigating arrhythmia risk in Hydroxychloroquine and Azithromycin treated COVID-19 patients using arrhythmia risk management plan.

AIMS: To assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using arrhythmia risk management plan. METHODS AND RESULTS: We retrospectively examined arrhythmia safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined arrhythmia risk management plan. The data was analyzed using R statistical package version 4.0.0. A two-tailed p-value<0.05 was considered significant. 81 patients were included from March 23rd to May 10th 2020. The median age was 59 years, 58.0% were female. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia. Fourteen patients (17.3%) experienced QTc ≥ 480 ms and 16 patients (19.8%) had an increase of QTc ≥ 60 ms. Seven patients (8.6%) had QTc prolongation of ≥ 500 ms. The treatment was discontinued in 4 patients (4.9%). None of the patients developed ventricular tachycardia. The risk factors significantly associated with QTc ≥ 500 ms were hypokalemia (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients (3.7%) died, the cause of death was bacterial superinfection with septic shock in two patients, and disseminated intravascular coagulation with multiple organ failure in one patient. None of these deaths were associated with cardiac arrhythmias. CONCLUSION: We recorded a low incidence of QTc prolongation ≥ 500 ms and no ventricular tachycardia events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia risk management plan.

Safety of expanded criteria for endoscopic resection of early gastric cancer in a Western cohort.

BACKGROUND: Endoscopic resection is widely accepted treatment option for early gastric cancer if tumors meet the standard or expanded indications. However, the safety of expanded criteria is still under investigation. Furthermore, discussion, if any additional treatment is necessary for patients who underwent endoscopic resection but exceeded expanded criteria, is rising. This study aimed to evaluate the safety of extended indications for endoscopic resection of early gastric cancer in a Western cohort. Also, we aimed to analyze the lymph node metastasis rate in tumors which exceeds the extended criteria. METHODS: Two hundred eighteen patients who underwent surgery for early gastric cancer at National Cancer Institute, Vilnius, Lithuania between 2005 and 2015 were identified from a prospective database. Lymph node status was examined in 197 patients who met or exceeded extended indications for endoscopic resection. RESULTS: Lymph node metastasis was detected in 1.7% of cancers who met extended indications and in 30.2% of cancers who exceeded expanded indications. Lymphovascular invasion and deeper tumor invasion is associated with lymph node metastasis in cancers exceeding expanded indications. CONCLUSIONS: Expanded criteria for endoscopic resection of early gastric cancer in Western settings is not entirely safe because these tumors carry the risk of lymph node metastasis.

Surgical treatment outcomes of patients with T1-T2 gastric cancer: does the age matter when excellent treatment results are expected?

BACKGROUND: The proportion of early gastric cancer stages is increasing, as is the incidence of gastric cancer among the elderly population. Therefore, this study was designed to analyze surgical treatment outcomes of T1-T2 gastric cancer in elderly patients. METHODS: A total of 457 patients with T1-T2 gastric cancer who underwent gastrectomy between 2005 and 2015 were enrolled in this retrospective study. Patients were classified into two groups according to age (< 70 years versus ≥ 70 years). Clinicopathological features, surgical treatment results, and clinical outcomes were compared between the groups. RESULTS: Higher ASA score (ASA 3/4), differentiated cancer, and intestinal-type tumors were more common in elderly patients. Postoperative complication rates were similar between the two groups; however, postoperative mortality rates were significantly higher in the elderly group. Higher ASA score was independently associated with postoperative complications in the elderly group. Furthermore, severe postoperative complications were found as an independent factor associated with higher 90-day mortality rate. Elderly patients had a significantly poorer 5-year overall survival rate. Two surgery-related factors-total gastrectomy and complicated postoperative course-were revealed as independent prognostic factors for poor overall survival in the elderly group. CONCLUSIONS: Despite higher postoperative mortality rate and poorer overall survival results, elderly patients with gastric cancer should be considered for radical surgery. ASA score may be useful for predicting surgical treatment outcomes in elderly patients undergoing surgery for GC and hence assists clinicians in planning treatment strategies for each individual patient.

Risk factors for lymph node metastasis in early gastric cancer patients: Report from Eastern Europe country- Lithuania.

BACKGROUND: Current risk factors for lymph node metastasis in early gastric cancer have been primarily determined in Asian countries; however their applicability to Western nations is under discussion. The aim of our study was to identify risk factors associated with lymph node metastasis in Western cohort patients from the Eastern European country - Lithuania. METHODS: A total of 218 patients who underwent open gastrectomy for early gastric cancer were included in this retrospective study. After histolopathological examination, risk factors for lymph node metastasis were evaluated. Overall survival was evaluated and factors associated with long-term outcomes were analyzed. RESULTS: Lymph node metastases were present in 19.7% of early gastric cancer cases. The rates were 5/99 (4.95%) for pT1a tumors and 38/119 (31.9%) for pT1b tumors. Submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation were identified as independent risk factors for lymph node metastasis. Submucosal tumor invasion and lymphovascular invasion were also associated with worse 5-year survival results. CONCLUSION: Our study established submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation as risk factors for lymph node metastasis.