Carlino, Matteo

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

Abstract 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. Demographics, disease characteristics, efficacy and toxicity were examined. Results: Forty-seven patients were identified from 12 centres. The response rate to [...]

June 28th, 2022|Comments Off on Re-induction ipilimumab following acquired resistance to combination ipilimumab and anti-PD-1 therapy.

Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma.

Abstract Purpose: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. Patients and methods: Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary [...]

November 24th, 2021|Comments Off on Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma.

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation.

Objectives: Parts 4 and 5 of the phase 1/2 KEYNOTE-022 study investigated the maximum tolerated dose (MTD), safety, and efficacy of pembrolizumab plus trametinib in solid tumours and BRAF wild-type melanoma. Patients and methods: Patients received intermittent or concurrent dosing of pembrolizumab plus trametinib. Concurrent dosing was 2 or 4 weeks of trametinib run-in followed by concurrent pembrolizumab every 3 weeks (Q3W) plus trametinib once daily (QD). Intermittent dosing was 2 weeks of trametinib run-in followed by pembrolizumab plus intermittent trametinib (1 week off/2 weeks on). A 3 + 3 dose escalation was used, followed by dose confirmation. Results: Forty-two patients were [...]

November 17th, 2021|Comments Off on KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation.

Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside.

Abstract Immune checkpoint inhibitors have transformed the landscape of oncological therapy, but at the price of a new array of immune related adverse events. Among these is β-cell failure, leading to checkpoint inhibitor-related autoimmune diabetes (CIADM) which entails substantial long-term morbidity. As our understanding of this novel disease grows, parallels and differences between CIADM and classic type 1 diabetes (T1D) may provide insights into the development of diabetes and identify novel potential therapeutic strategies. In this review, we outline the knowledge across the disciplines of endocrinology, oncology and immunology regarding the pathogenesis of CIADM and identify possible management strategies. [...]

November 5th, 2021|Comments Off on Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside.

Antitumor Activity of Ipilimumab or BRAF ± MEK Inhibition After Pembrolizumab in Patients With Advanced Melanoma: Analysis from KEYNOTE-006.

Abstract Background: Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized. Patients and methods: In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi ± MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled. Results: At data cut-off (4 December 2017), median follow-up was 46.9 [...]

October 25th, 2021|Comments Off on Antitumor Activity of Ipilimumab or BRAF ± MEK Inhibition After Pembrolizumab in Patients With Advanced Melanoma: Analysis from KEYNOTE-006.

Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition – A Descriptive Observational Retrospective Multicenter Analysis.

Abstract Introduction: Immune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia. Methods: This multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinical characteristics, diagnostics, [...]

October 21st, 2021|Comments Off on Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition – A Descriptive Observational Retrospective Multicenter Analysis.

Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy

Abstract Background: Immune checkpoint inhibitors (ICIs) are approved to treat multiple cancers. Retrospective analyses demonstrate acceptable safety of ICIs in most patients with autoimmune disease, although disease exacerbation may occur. Psoriasis vulgaris is a common, immune-mediated disease, and outcomes of ICI treatment in patients with psoriasis are not well described. Thus we sought to define the safety profile and effectiveness of ICIs in patients with pre-existing psoriasis. Methods: In this retrospective cohort study, patients from eight academic centers with pre-existing psoriasis who received ICI treatment for cancer were evaluated. Main safety outcomes were psoriasis exacerbation and immune-related adverse events (irAEs). We [...]

October 11th, 2021|Comments Off on Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy

Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006.

Abstract Objective: Patients with melanoma and early stable disease (SD) with pembrolizumab have unclear prognosis. We present post hoc analyses of long-term outcomes for patients with early SD, partial response (PR) or complete response (CR) with pembrolizumab. Patients and methods: Patients who received pembrolizumab in the KEYNOTE-001 and KEYNOTE-006 studies and had SD, PR or CR at weeks 12 or 24 were included. Results: Of 294 patients in the week 12 analysis, 107 (36.4%) had SD at week 12, of whom 7 (6.5%) had a best overall response of CR, 43 (40.2%) had PR and 57 (53.3%) had SD. Forty-eight-month overall survival [...]

September 24th, 2021|Comments Off on Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006.

Immune checkpoint inhibitors in melanoma

Abstract Immune checkpoint inhibitors target the dysfunctional immune system, to induce cancer-cell killing by CD8-positive T cells. Immune checkpoint inhibitors, specifically anti-CTLA4 and anti-PD-1 antibodies, have revolutionised the management of many cancers, particularly advanced melanoma, for which tumour regression and long-term durable cancer control is possible in nearly 50% of patients, compared with less than 10% historically. Despite the absence of adequately powered trial data, combined anti-CTLA4 and anti-PD-1 checkpoint inhibition has the highest 5-year overall survival rate of all therapies in advanced melanoma, and has high activity in melanoma brain metastases. A phase 3 study has shown the [...]

September 11th, 2021|Comments Off on Immune checkpoint inhibitors in melanoma

Adjuvant immunotherapy recommendations for stage III melanoma: physician and nurse interviews.

Abstract Background: Adjuvant immunotherapy is revolutionising care for patients with resected stage III and IV melanoma. However, immunotherapy may be associated with toxicity, making treatment decisions complicated. This study aimed to identify factors physicians and nurses considered regarding adjuvant immunotherapy for melanoma. Methods: In-depth interviews were conducted with physicians (medical oncologists, surgeons and dermatologists) and nurses managing patients with resected stage III melanoma at three Australian tertiary melanoma centres between July 2019 and March 2020. Factors considered regarding adjuvant immunotherapy were explored. Recruitment continued until data saturation and thematic analysis was undertaken. Results: Twenty-five physicians and nurses, aged 28-68 years, 60% females, [...]

September 10th, 2021|Comments Off on Adjuvant immunotherapy recommendations for stage III melanoma: physician and nurse interviews.
Go to Top