CDK4/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset.

Introduction: CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib) are 1st line therapy in metastatic breast cancer (MBC). No comparative data exists between agents regarding toxicity or efficacy.

Methods: A retrospective study was performed at our tertiary referral centre evaluating patients on a CDK4/6 inhibitor for MBC between July 2017 and December 2021.

Neurological adverse effects associated with anti-PD1 antibodies alone or in combination with ipilimumab: a multicenter case series.

Anti-programmed cell death protein 1 (PD1) antibodies, pembrolizumab and nivolumab, alone or in combination with ipilimumab, have become standard treatment for melanoma and multiple other malignancies. Neurological adverse effects are rare and have not been well characterized to date. Patients who developed neurological adverse effects while being treated with PD1, alone or in combination with ipilimumab, were retrospectively identified from 10 cancer centers.

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics.

Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0).

Management of immune-related hepatitis in patients being treated with checkpoint inhibitors for metastatic melanoma, a review and case series.

Introduction: Immune-related hepatitis is an adverse effect following treatment with immune-checkpoint inhibitors, such as ipilimumab, nivolumab and pembrolizumab. International guidelines advise on the use of corticosteroids as first-line treatment, although guidance on how to treat cases resistant to corticosteroids is limited. We aimed to evaluate the presentation and management of patients with grade 3-4 immune-related hepatitis, following treatment with immune-checkpoint inhibitors for stage 4 or unresectable or stage 3 melanoma, with a particular focus on steroid-refractory cases.

Eosinophilic Asthma Secondary to Adjuvant Anti-PD-1 Immune Checkpoint Inhibitor Treatment in a Melanoma Patient.

Background: Adjuvant immune checkpoint inhibitors are a new standard of care in melanoma. However, the immune related toxicity associated with these agents can be serious, and the long-term implications are yet to be defined especially in the adjuvant setting. We report, to our knowledge, the first case of anti-PD-1-induced eosinophilic asthma in a melanoma patient treated with adjuvant pembrolizumab.

Benefit and toxicity of programmed death-1 blockade vary by ethnicity in patients with advanced melanoma: an international multicentre observational study.

Background: Programmed cell death receptor-1 (PD-1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in white populations and remain poorly characterized in other ethnic groups, such as East Asian, Hispanic and African.

Objectives: To determine the efficacy and toxicity of PD-1 monotherapy in different ethnic groups.

Methods: Clinical data for patients with unresectable or advanced melanoma treated with anti-PD-1 monotherapy between 2009 and 2019 were collected retrospectively from five independent institutions in the USA, Australia and China.

Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti-PD-1 Monotherapy.

Purpose: Programmed cell death receptor-1 (PD-1) inhibitors are frontline therapy in advanced melanoma. Severe immune-related adverse effects (irAEs) often require immunosuppressive treatment with glucocorticoids (GCCs), but GCC use and its correlation with patient survival outcomes during anti-PD-1 monotherapy remains unclear.

Experimental Design: In this multicenter retrospective analysis, patients treated with anti-PD-1 monotherapy between 2009 and 2019 and detailed GCC use, data were identified from five independent cohorts, with median follow-up time of 206 weeks.

Re-induction ipilimumab following acquired resistance to combination ipilimumab and anti-PD-1 therapy.

Purpose: Combination immunotherapy with nivolumab and ipilimumab has a high initial response rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to combination immunotherapy is unknown.

Methods: Patients with advanced melanoma who initially achieved a complete response, partial response or sustained stable disease to induction combination immunotherapy then progressed and were reinduced with ipilimumab (alone or in combination with anti-PD-1) and were analysed retrospectively.

Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis.

Background: Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown.

Methods: Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included.

Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts.

Rapid production of neutralizing antibody can be critical for limiting the spread of infection. Such early antibody results when B-cell blasts mature directly to plasmablasts without forming germinal centers. These extrafollicular responses can involve Ig class switch recombination (CSR), producing antibody that can readily disseminate through infected tissues.

ANCA-associated vasculitis: from bench research to novel treatments.

Small-vessel vasculitic syndromes such as Wegener granulomatosis and microscopic polyangiitis, which are associated with circulating antineutrophil cytoplasmic autoantibodies, are an important cause of renal failure. Current immunosuppressive regimens based on cyclophosphamide have significantly improved survival in patients with these conditions. However, such treatments are toxic, increase the risk of infection and do not cure the disease; fresh approaches are, therefore, required.

Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia.

Disease relapse is a major cause of treatment failure after reduced-intensity allografts and while donor lymphocyte infusions (DLIs) can be effective salvage therapy they are associated with severe graft-versus-host disease (GVHD) when administered early after transplantation. We have therefore examined whether imatinib mesylate can delay relapse and postpone the requirement for DLI in 22 patients with chronic myeloid leukemia (CML) allografted using a reduced-intensity regimen. Imatinib was commenced on day + 35 and continued until 1 year after transplantation.