A phase 2 study of ibrutinib maintenance following first-line high-dose methotrexate-based chemotherapy for elderly patients with primary central nervous system lymphoma.

BACKGROUND: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression-free survival (PFS) of 6-16 months. Ibrutinib penetrates the blood-brain barrier and has shown activity in PCNSL. METHODS: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2-year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60-85 years old who responded to first-line high-dose methotrexate (HDMTX)-based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity. RESULTS: Twenty patients were enrolled, with a median age of 72 years (range, 61-80). Median time on ibrutinib maintenance was 12.5 (range, 2-46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1- and 2-year PFS are 90% and 72.6%, respectively, and the 2-year OS is 89%. CONCLUSIONS: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly.

A retrospective study of 222 patients with newly diagnosed primary central nervous system lymphoma-Outcomes indicative for improved survival overtime.

Primary central nervous system lymphoma (PCNSL) is a rare disease with an incidence of 0.4/per 100,000 person-years. As there is a limited number of prospective randomized trials in PCNSL, large retrospective studies on this rare disease may yield information that might prove useful for the future design of randomized clinical trials. We retrospectively analyzed the data of 222 newly diagnosed PCNSL patients treated in five referral centers in Israel between 2001 and 2020. During this period, combination therapy became the treatment of choice, rituximab has been added to the induction therapy, and consolidation with irradiation was largely laid off and was mostly replaced by high-dose chemotherapy with or without autologous stem cell transplantation (HDC-ASCT). Patients older than 60 comprised 67.5% of the study population. First-line treatment included high-dose methotrexate (HD-MTX) in 94% of patients with a median MTX dose of 3.5 g/m2 (range 1.14-6 g/m2 ) and a median cycle number of 5 (range 1-16). Rituximab was given to 136 patients (61%) and consolidation treatment to 124 patients (58%). Patients treated after 2012 received significantly more treatment with HD-MTX and rituximab, more consolidation treatments, and autologous stem cell transplantation. The overall response rate was 85% and the complete response (CR)/unconfirmed CR rate was 62.1%. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were 21.9 and 43.5 months respectively with a significant improvement since 2012 (PFS: 12.5 vs. 34.2 p = 0.006 and OS: 19.9 vs. 77.3 p = 0.0003). A multivariate analysis found that the most important factors related to OS were obtaining a CR followed by rituximab treatment and Eastern Cooperative Oncology Group performance status. The observed improvement in outcomes may be due to multiple components such as an intention to treat all patients regardless of age with HD-MTX-based combination chemotherapy, treatment in dedicated centers, and more aggressive consolidation with the introduction of HDC-ASCT.

New-onset systemic lupus erythematosus following BNT162b2 mRNA COVID-19 vaccine: a case series and literature review.

Emerging data evaluated the possible link between the Coronavirus 19 (COVID-19) vaccine and acute flares of rheumatic autoimmune diseases. However, the association between the COVID-19 vaccine and the development of de-novo rheumatic autoimmune diseases remained unclear. We report the first case series of three male patients who developed new-onset systemic lupus erythematosus following receiving Pfizer BNT162b2 mRNA vaccination. The clinical characteristics share some similarities with drug-induced lupus. More patients with SLE following COVID-19 may be diagnosed in the future. Additional studies will provide more significant insights into the possible immunogenic influence of the COVID-19 vaccine.

[ETHNIC DIVERSITY AND CLINICAL CHARACTERISTICS OF HOSPITALIZED PATIENTS WITH ACUTE PANCREATITIS].

BACKGROUND: Previous studies have shown a correlation between acute pancreatitis and several different risk factors that vary in different countries and ethnic groups. The aims of this study are to examine the clinical characteristics and outcomes of acute pancreatitis in patients of Jewish and Bedouin origin. METHODS: We performed a retrospective cohort study of patients hospitalized with acute pancreatitis in the Soroka University Medical Center between the years 2012 and 2016 and compared two groups of patients: patients of Jewish and Bedouin origin. The primary outcome was a composite outcome consisting of 30-days mortality, ICU admission, complications (defined as necrotizing pancreatitis or pseudocyst formation), surgery due to these complications and 30-days re-admission due to pancreatitis. RESULTS: A total of 560 patients were included, 483 patients (86.3%) of Jewish origin and 77 patients (13.7%) of Bedouin origin. The most common cause in both groups was biliary pancreatitis: 49.7% among Jewish, 61% among Bedouin. In our study alcohol consumption, the most common worldwide risk factor of pancreatitis, accounts for only a small percentage of the disease in the Jewish population (5.6%) and does not exist in the Bedouin population. We found no significant differences in outcomes between the two groups. CONCLUSIONS: Biliary pancreatitis was the most common cause in both groups of patients. The important finding of our study is that alcohol use is a minor cause of acute pancreatitis in the Negev. Moreover, it is uncommon in the Jewish population and is completely non-existent among Bedouins. No differences were found in the primary outcomes between the two groups.

Clinical, Epidemiological, and Etiological Changes in Erythema Nodosum.

BACKGROUND: Erythema nodosum (EN) is the most common type of panniculitis, commonly secondary to infectious diseases. OBJECTIVES: To elucidate the causative factors and the clinical presentation of patients with EN (2004-2014) and to compare their data to those reported in a previous study. METHODS: A retrospective study was conducted of all patients diagnosed with EN who were hospitalized at Soroka University Medical Center (2004-2014). The clinical, demographic, and laboratory characteristics of the patients were compared to those in a cohort of patients diagnosed with EN from 1973-1982. RESULTS: The study comprised 45 patients with a diagnosis of EN. The most common symptoms of patients hospitalized with EN were arthritis or arthralgia (27% of patients). Patients with EN, compared to those reported in 1987, has significantly lower rates of fever (18% vs. 62% P < 0.001), streptococcal infection (16% vs. 44%, P = 0.003), and joint involvement (27% vs. 66%, P < 0.001). In addition, fewer patients had idiopathic causes of EN (9% vs. 32%, P = 0.006). CONCLUSIONS: In the past decades, clinical, epidemiological, and etiological changes have occurred in EN patients. The lowering in rate of fever, streptococcal infection, and joint involvement in patients with EN are probably explained by improvements in socioeconomic conditions. The significantly decreasing rate of idiopathic causes of EN is possibly due to the greater diagnostic accuracy of modern medicine. The results of the present study demonstrate the impact of improvements in socioeconomic conditions and access to healthcare on disease presentation.

An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

Progressive Transformation of Germinal Centers Simulating Malignant Axillary Lymphadenopathy in a Breast Cancer Patient on FDG PET/CT.

ABSTRACT: A 64-year-old woman with breast cancer underwent FDG PET/CT for follow-up. The study revealed highly increased FDG uptake in newly diagnosed enlarged axillary lymph nodes, which were worrisome for malignancy. Histopathology revealed a rarely diagnosed benign disease of progressive transformation of germinal centers mimicking malignant lymphadenopathy. As imaging findings of this entity, which usually involves the axillary and cervical areas, have been reported in very few studies, nuclear medicine physicians should be familiar with this potential "false-positive" FDG uptake representing an interpretative pitfall, especially during evaluation of breast cancer patients.

Clinical Characteristics and Prognosis of Idiopathic Acute Pancreatitis.

OBJECTIVE: Acute pancreatitis is a serious diagnosis with an increasing incidence in the Western world. In this study we sought to investigate the incidence of idiopathic AP and to compare clinical and prognostic characteristics of idiopathic cases with cases of AP with known etiology. METHODS: In this retrospective study of adult hospitalized patients diagnosed with acute pancreatitis between 2012 and 2015, a comparison was made between admissions of patients with known etiology and those for whom no cause was found. Primary outcome was defined as composite outcome of 30-day mortality and complications. RESULTS: Among 560 admissions of 437 patients with a primary diagnosis of acute pancreatitis, the main factors identified were gallstones (51.2%) and idiopathic pancreatitis (35.9%), with alcohol ranked third at only 4.8%. Mortality rate within 30 days of hospitalization was 2.9% and within one year was 7.1%. Use of lipid-lowering, anti-hypertensive, and anti-diabetic medications was more frequent among patients with "idiopathic" disease (70%, 68%, and 33% versus 59%, 56%, and 27%, respectively). Patients admitted with idiopathic AP, in comparison to patients with known AP etiology, had milder disease with shorter hospital stay (3 days versus 4, respectively), and less re-admission in 30 days (7.5% versus 21.2%). Idiopathic AP patients had better prognosis in terms of 30-day death and complication (HR 0.33, 95% CI 0.08-0.40, P<0.001). CONCLUSION: Idiopathic disease is common among acute pancreatitis patients; the two study groups differed in severity of disease and prognosis. Common use of medications with doubtful value suggests possible under-diagnosis of drug-induced acute idiopathic pancreatitis.