Immune-related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with irAEs: a single-center experience.

BACKGROUND: Given the widespread use of immune checkpoint inhibitors (ICIs), newer immune related adverse events (irAEs) have come to light, including flare-ups of preexisting autoimmune disorders (AIDs) and delayed immune-related events. We aimed to identify the frequency and severity of new IRAEs, including AID flares in cancer patients treated with ICIs at our institution. We also studied the tolerability of ICIs upon rechallenge in patients with irAEs and hospital admissions due to irAEs in a community setting in rural Maine. METHODS: We conducted a retrospective chart review analysis of all patients with cancer who received anti-PDL1/PDL1 inhibitors nivolumab, pembrolizumab, atezolizumab, and durvalumab at our tertiary care center from November 2015 to March 2019. Demographic data, cancer type and stage, irAEs, hospital admissions due to irAEs, and drug treatment information was extracted. RESULTS: We included 465 patients who received ICIs, 115 (out of 465 25%) developed new irAEs. Preexisting AID were identified in 47 (out of 465) (10%), AID flares were observed in 12 patients (25% of 47). 17 (out of 47 36%) were on immunosuppression for underlying AID, 5 (out of 17, 29%) developed flares. Overall, 148 (32% of 465) irAEs occurred, as some patients had multiple toxicities. Majority were treated for Lung cancer (63%), followed by melanoma and genitourinary cancers. Due to irAE severity, treatment was permanently discontinued in 15% (out of 465) patients. Hospital admissions due to irAEs were required for 34 patients (7.3% of 465). ICI rechallenge was performed in 27 patients (6% of 465), and majority tolerated well. CONCLUSION: Our study shows that ICIs were generally well tolerated and can be used safely even in patients with preexisting AIDs; it is encouraging to see majority tolerated rechallenge with ICIs well.

Medically Refractory Multiple Sclerosis Is Successfully Treated with Plasmapheresis in a Super Morbidly Obese Pregnant Patient.

Multiple sclerosis (MS) is a relapse remitting immune-mediated demyelinating neurological disorder that primarily affects women of childbearing age. In most patients, the hormonal changes during pregnancy are protective against MS relapses. When relapses do occur, treatment options are limited to use of intravenous steroids and plasmapheresis rescue therapy. We present a case of steroid refractory MS-transverse myelitis with quadriplegia in a 25-year-old pregnant super morbidly obese woman. Our clinical case is unique because the severity of her relapse early in pregnancy, which was intractable and resistant to steroids. This may have been a rebound demyelination due to the discontinuation of fingolimod; a newly recognized entity by the FDA. Our case report therefore seeks to raise awareness about a potential complication of discontinuing MS disease modifying therapies, highlighting that these rebound relapses can be steroid resistant and occur despite the usual protective hormonal influence of early pregnancy and that plasma exchange is a valid treatment option. Finally, we discuss the challenges of determining exchange volumes for plasmapheresis in the super morbid obese population to secure good maternal and fetal outcomes.

Vanishing bile duct syndrome as a manifestation of Hodgkin's lymphoma: a case report and review of the literature.

Vanishing bile duct syndrome (VBDS) is characterized by cholestasis and progressive destruction of the intrahepatic bile ducts (ductopenia). The current definition of ductopenia is the loss of interlobular bile ducts in more than 50% of portal tracts. Ductopenia is believed, at a molecular level, to result from the misbalance in cell regeneration and apoptosis. In the literature various etiologies have been reported to cause ductopenia, with Hodgkin's lymphoma (HL) being listed as a rare example. How HL causes ductopenia remains ambiguous, and seems to be related to a paraneoplastic phenomenon causing cytokine release from lymphoma cells, not tumor infiltration or obstructive lymphadenopathy. VBDS is generally considered irreversible, unlike its histopathological counterpart, idiopathic cholestasis, where ductopenia is not present and liver function improves with therapy. Therefore, a distinction between the two is warranted. There have been only 19 case reports in the English literature associating VBDS with HL. Here we report a 64-year-old female patient who presented with distributive shock and jaundice. Initial laboratory values revealed leukocytosis, mild transaminase elevation with significantly elevated alkaline phosphatase, along with direct hyperbilirubinemia. During hospital stay, the patient's liver function progressively worsened. Further workup did not reveal ductal dilation or obstruction and there were unremarkable results for infectious and autoimmune etiologies. Imaging studies with biopsy revealed extensive lymphadenopathy consistent with HL; liver biopsy showed cholestasis and ductopenia. Despite chemotherapy the patient succumbed to progressive liver failure and sepsis.

Acute myeloid leukemia and diabetes insipidus with monosomy 7.

The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480) than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.

Treating octogenarian and nonagenarian acute myeloid leukemia patients--predictive prognostic models.

BACKGROUND: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed, including the use of a comorbidity index. However, it is unclear whether the Charlson comorbidity index (CCI) or the hematopoietic cell transplant comorbidity index (HCTCI) is more sensitive. METHODS: The authors analyzed their experience with 92 patients aged >or=80 years who had AML. Patients' pretreatment characteristics and their treatment outcomes were recorded. RESULTS: All patients were offered intensive treatment; 59 patients (64%) were treated intensively with a variety of regimens, whereas 33 patients (36%) elected to receive supportive care. The CCI and the HCTCI had similar predictive ability for outcome in both groups. A multivariate analyses of prognostic factors identified near-normal albumin (48% of patients; 1-year survival rate, >27%) as a favorable factor for the whole cohort, age <83 years (47% of patients; 1-year survival rate, >25%) and nonmonocytic morphology (75% of patients; 1-year survival rate, >26%) as favorable factors for the intensively treated cohort, and bone marrow blasts <46% (50% of patients; 1-year survival rate, >19%) as a favorable factor for patients who received supportive care. CONCLUSIONS: This retrospective analysis was developed to assist in treatment decisions for octogenarian and nonagenarian patients with AML. The findings will need validation in a prospective study.