Dataset Information

The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

ABSTRACT:

Background

Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established.

Methods

Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0).

Results

Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15-24.88, P=0.033; OR=5.23, 95% CI: 1.41-19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09-11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: -4.48 to -1.79%, P<0.001). A loss of SMA ?7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P=0.046).

Conclusions

Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation.

SUBMITTER: Daly LE

PROVIDER: S-EPMC5294486 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

Daly Louise E LE Power Derek G DG O'Reilly Áine Á Donnellan Paul P Cushen Samantha J SJ O'Sullivan Kathleen K Twomey Maria M Woodlock David P DP Redmond Henry P HP Ryan Aoife M AM

British journal of cancer 20170110 3

<h4>Background</h4>Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established.<h4>Methods</h4>Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline ...[more]

PMID: 28072766

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Project description:BackgroundAn improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma.MethodsA total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival.ResultsThe median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events.ConclusionsIpilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

Project description:IntroductionImmunotherapy has revolutionized metastatic Melanoma therapy. The most active regimen is combination therapy of Ipilimumab-Nivolumab (Ipi-Nivo) with response rates (RR) of ~60% and median overall survival (OS) of ~6 years. Immune-related adverse events (irAE) are common (~60% develop grade 3-4) and pose a challenge when treating frail patients. We sought to examine whether Ipi-Nivo therapy is feasible in elderly metastatic melanoma patients.MethodsElectronic records of patients treated at the Ella Lemelbaum Institute with Ipi-Nivo between the years 2017-2021 were screened for age. Elderly patients were defined as age 75 and older (group A) and were matched with records of patients age <75 (group B). Records were analyzed for baseline parameters, immunotherapy regimen, RR, toxicity and progression-free survival (PFS).ResultsTwenty-six relevant patients age >75 (median 77) were identified and were matched to 34 younger patients (median age 57). No statistically significant differences were noted in terms of baseline parameters except for BRAF mutation status (group A 15%, group B 47%, p=0.008). Response rate in group A was 38% and is consistent with previously published data. Median PFS was the same for both groups (A = 5.5 months, B= 7.5 months, p=NS). Treatment was similarly tolerated: 35% of group A patients completed 4 cycles of therapy compared to 28% for group B (p=NS). Grade 2-4 irAE were the same (A=58%, B=66%, p=NS) and there was no difference in the need for hospitalization for G3-4 events between the groups. (A=63%, B=69%, p=NS). Further division into 4 age groups (>80 vs 75-79 in group A and 65-74 vs <65 in group B) found no difference in terms of response rate or G3-4 toxicity.ConclusionIpilimumab-Nivolumab combination therapy in elderly metastatic Melanoma patients seems to be well tolerated and efficient in selected elderly patients based on performance status and comorbidities, just as in younger patients. This regimen seems to be a feasible treatment option for this age group.

Dataset Information

The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

Background

Methods

Results

Conclusions

Publications

The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

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