Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma

10046 Background: Immune checkpoint blockade (ICB) has changed the natural history advanced melanoma (AM). Based on phase III trial, which used RECIST criteria, the complete response (CR) rate with anti-PD1 therapy is around 20%. In daily practice, PET/CT is a useful tool to evaluate response to treatment in melanoma patients. Little is known about the number of patients who achieve metabolic CR by PET/CT but with anatomic residual disease and their prognosis. Methods: We conducted a retrospective analysis of patients with AM treated with ICB who achieved metabolic CR by PET/CT but with residual disease on tomography and compared to patients with RECIST CR in a high-volume cancer center. Progression-free (PFS) and overall survival (OS) were obtained by Kaplan Meier method and log-rank test. Results: One hundred seventy pts with AM treated with anti-PD1 (79%) or anti-PD1 + anti- CTLA4 (21%) betweenSeptember 2013 and December 2019 were analyzed. At a median follow-up of 23.6 months, seventy-five (44%) pts achieved CR. RECIST criteria: 22 pts (29.3%) and metabolic CR: 53 pts (70.7%). All patients with metabolic CR had RECIST partial response. The median total time on treatment was 14.8m (95%CI:0.9-42.3). The median time to reach CR was 5.4m (95%CI: 3-39). The median time of treatment after CR was 6.8m (95%CI: 0-21.4). The rate of CR patients off treatment at the moment of this analysis was 69%. The median follow-up after discontinuing treatment was 5.2m. There was no difference in PFS (36 month-rate: 84.4% vs 74%, p:0.64) and OS (36 month-rate: 100% vs 86.3%, p:0.14) between pts with CR based on RECIST or PET-CT, respectively. Median time for PFS and OS have not been reached until the date cut-off. Nine pts have relapsed (12%). Seven of them had residual disease on tomography but with no metabolic active lesion(s) at the time of the end of treatment. Conclusions: Twice more patients achieve complete response considering only metabolic parameters on PET/CT compared to RECIST criteria and they seem to have comparable prognosis.

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Bone metastasis as an independent prognostic factor for survival in patients with advanced melanoma treated with immune checkpoint blockade.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22045 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22045-e22045

Author(s):

Marcos Rezende Teixeira ◽

Milton Jos De Barros E Silva ◽

Natasha Carvalho Pandolfi ◽

Vinicius Fernando Calsavara ◽

Thiago Bueno Oliveira ◽

...

Keyword(s):

Overall Survival ◽

Bone Metastasis ◽

Prognostic Factor ◽

Immune Checkpoint ◽

Cox Regression ◽

Immune Checkpoint Blockade ◽

Advanced Melanoma ◽

Independent Prognostic Factor ◽

Checkpoint Blockade ◽

The Impact

e22045 Background: Immune checkpoint blockade (ICB) has changed the natural history advanced melanoma (AM) with response rates about 40% and overall survival in 5 years of more than 30%. Interestingly, the site of metastasis may have impact on immune response due to the quantity and quality of immune infiltrate as we have seen in patients (pts) with liver metastasis treated with ICB. We have hypothesized that bone metastasis(BM) represents an immune less responsive site of disease Methods: We conducted a retrospective observational analysis of patients with AM treated with ICB at A.C. Camargo Cancer Center (AC) in São Paulo, Brazil. We analyze the impact of BM on progression-free (PFS) and overall survival (OS) using Kaplan Meier method, log-rank test and time-dependent COX regression model. Results: We analyzed 170 pts with AM treated with anti-PD1 (79%) or anti-PD1 + anti-CTLA4 (21%) between September 2013 and December 2019. Fifty-five percent in first-line, 22.4% second-line and the remaining in third or more lines of therapy. Ninety- four were male (55.3%), median age of 60.5 years (24.8 to 88.3) and 61 (35.9%) pts had BRAF mutation. Among stage IV patients (94%), 52 (32.4%) were M1c, 36 (22.4%) M1d and 46 (27%) had elevated LDH. Forty-two (26%) pts had BM. The overall response rate was 30.9% for pts with BM compared to 57.7% for pts without BM (p:0.004). In a median follow-up of 23.6 months (95% CI: 18.0-29.1), the median PFS and OS for pts with and without BM were 3.8 x 18.8 months (p 0.005) and 19.4months x not achieved (p 0.001), respectively. The 24-month analysis shows an overall survival rate of 38% for patients with BM compared to 62% for the rest of the cohort population. In a multivariate analysis for overall survival, acral melanoma, elevated LDH, ECOG performance status of 1 or 2 and BM were independent adverse prognostic factors (bone metastasis - HR: 2.3; 95%CI: 1.18-4.1; p:0.013). Conclusions: In this analysis, the presence of bone disease seems to be a worse independent prognostic factor for survival. A hypothesis would be the unfavorable bone microenvironment for the action of the immunotherapy.

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