Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies.

BACKGROUND: This report provides a survival update at a follow-up of >5 years (5.5-6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported. PATIENTS AND METHODS: Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025. RESULTS: Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%-16.5%, and 15.5%-28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%-49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively. CONCLUSIONS: At a follow-up of 5-6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS. CLINICALTRIALSGOV: NCT00162123.

Treatment patterns and outcomes among patients diagnosed with unresectable stage III or IV melanoma in Europe: a retrospective, longitudinal survey (MELODY study).

BACKGROUND: MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal surveY (MELODY), the first multicountry, observational survey in patients with advanced melanoma, aimed to quantify the impact of existing treatment strategies by capturing information on treatment patterns and clinical outcomes. PATIENTS AND METHODS: Patients attending a participating site between 1st July 2005 and 30th June 2006 with ≥2 months follow-up were eligible. Data were retrieved retrospectively from advanced melanoma diagnosis until 1st May 2008. Treatment data were collected by line of therapy and response and progression-free survival data by line of systemic treatment. Overall survival (OS) was evaluated for all treated patients. RESULTS: Among all patients screened, 776 were eligible for this analysis. Median OS from the date of advanced disease diagnosis was 16.4 months. After excluding patients diagnosed prior to 1st July 2005 to account for any bias resulting from patient selection, the 12-month survival rate and median OS from the start date of second-line treatment was 28.8% and 6.8 months, respectively. Survival was lower in patients with brain metastases, elevated lactate dehydrogenase levels and more advanced disease. Rates of complete/partial tumour response were 15% and 7% in patients treated with first- and second-line systemic therapy, respectively. CONCLUSIONS: Despite receiving first- and second-line treatment, most patients with advanced melanoma have short survival times and poor prognoses, reinforcing the need for new treatments.

Economic impact of healthcare resource utilisation patterns among patients diagnosed with advanced melanoma in the United Kingdom, Italy, and France: results from a retrospective, longitudinal survey (MELODY study).

OBJECTIVE: To describe patterns of healthcare resource utilisation and associated costs for patients with advanced melanoma in the United Kingdom (UK), Italy, and France. METHODS: For patients receiving systemic treatment, or supportive care, data describing hospitalisations, hospice care, and outpatient visits were retrieved retrospectively from advanced disease diagnosis as part of a multicountry observational study. Costs were estimated by multiplying utilisation level by unit cost. In an exploratory analysis, costs were compared between individuals who died within one year of initiating first-line treatment (short-term survivors) and those with ≥ 1 year follow-up (long-term survivors). RESULTS: Hospitalisation costs were highest in France (€6262 per-person compared with €3225 in the UK and €2486 in Italy), reflecting higher rates of hospitalisation. In contrast, outpatient costs were highest in the UK (€782 per-person, compared with €115 in France and €72 in Italy), reflecting the highest rate and frequency of outpatient visits and the highest cost per visit. Hospitalisation rates were consistently higher during supportive care compared with systemic therapy. Roughly one-third of patients entered clinical trials and were not included in the analysis. In exploratory analysis, total costs were generally higher for long-term survivors, but monthly per-patient costs were generally lower for long-term survivors, consistent with a hypothesis that resource utilisation and costs do not necessarily increase proportionally with extended survival. CONCLUSION: Total costs associated with resource utilisation for advanced melanoma patients varied across countries. Overall cost differences were due to differences in frequency and intensity of utilisation patterns and variation in unit costs of health resources.

Occupational Plasmodium falciparum malaria following accidental blood exposure: a case, published reports and considerations for post-exposure prophylaxis.

A French nurse presented Plasmodium falciparum malaria 10 d after a needlestick while sampling blood in a source patient with malaria. As did the source patient, the nurse recovered fully although diagnosis was delayed and her malaria severe. We proceeded to a thorough description of the transmission profile of P. falciparum following occupational needlestick. A review of the literature found 21 published reports of occupational malaria including our own, documenting 22 P. falciparum infections. One of these was lethal. The mean incubation time to fever onset was documented in 21 reports including our own and is 11.60 +/- 3.38 d (median 12.0, range 4-17 d). The incubation period was compatible to that found in experimental anopheline bites or transfusion malaria. The transmission profile cites a pathogen which may be more easily transmissible by occupational exposure to blood than human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Undiagnosed malaria in non-immune health care workers can be lethal. Presumptive treatment of malaria is widely available and well tolerated. Clinicians should consider P. falciparum malaria when faced with a febrile patient who has or may have been exposed to biological fluids. Further research is needed in the field of P. falciparum prophylaxis following accidental exposure to a malaria patient's blood.