Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capillary Hyperplasia Following Treatment with Camrelizumab: A Retrospective Case-Control Study

Case Report

J Dis Markers. 2021; 6(2): 1044.

Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capillary Hyperplasia Following Treatment with Camrelizumab: A Retrospective Case-Control Study

Wang X¹, Long Q¹, He Q¹, Li J¹, Su Y², Zhao JY³* and Li F¹*

¹Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China

²Department of Ophthalmology, Anhui Provincial Children’s Hospital, Hefei 230000, Anhui Province, China

³Department of Pediatric Oncology Center, Beijing Children Hospital, Capital Meidical University, National Center for Children’s Health, China

*Corresponding author: Junyang Zhao, Department of Pediatric Oncology Center, Beijing Children Hospital, Capital Meidical University, National Center for Children’s Health, China

Fanfan Li, Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China

Received: June 22, 2021; Accepted: July 15, 2021; Published: July 22, 2021


Objective: To investigate the difference of clinical outcomes between patients with and without Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) after camrelizumab treatment. Methods: A retrospective, matched case-control study was designed. A total of 92 patients with advanced solid tumors treated with camrelizumab at xx hospital between July 2019 and October 2020 were included, of whom 16 patients developed RCCEP (RCCEP group) and the remaining 76 served as the control group. The primary endpoint is Progression-Free Survival (PFS), and the secondary endpoint is Objective Response Rate (ORR) and Overall Survival (OS). Multivariate Cox regression analysis is used to assess the relevant indicators of PFS.

Results: Compared with the control group, significantly increased ORR was observed in patients with RCCEP (56.3% vs 19.7%) (P<0.05). The PFS was 13 months (5-15 months) in the RCCEP group and 6 months (2-11 months) in the control group. Compared with the control group, the PFS was significantly higher in the RCCEP group (HR=0.555, 95% CI: 0.278-0.985, P<0.05). In multivariate Cox regression, RCCEP remained statistically significant after excluding potential confounders (HR=0.312, 95% CI: 0.095-0.637, P<0.01) and was associated with PFS in patients.

Conclusion: In camrelizumab treatment, the occurrence of RCCEP may be a marker of strong immune response and improved tumor treatment outcomes, and has potential predictive value in patient efficacy and prognosis.

Keywords: Camrelizumab; Advanced tumors; Reactive cutaneous capillary endothelial proliferation; Prognosis


Malignant tumors have become the primary disease threatening the life and health of all mankind [1]. In China, due to lifestyle changes and increasing aging and other factors, the incidence and mortality of malignant tumors are increasing rapidly every year, which leads to a significant increase in the number of patients with advanced malignant tumors [2]. Essentially all such patients develop metastases, and surgical treatment is of limited significance. Continued advances in chemotherapy, as well as targeted therapeutic approaches, have provided more promising treatment options for patients with advanced solid tumors [3,4].

Programmed Death receptor 1 (PD-1)/Programmed Death- Ligand 1 (PD-L1) signaling pathway has been widely studied in clinical practice in recent years. As one of the key links of immune checkpoints in tumor immune escape, it plays an important role in tumor immune escape [5]. Currently, PD-1/PD-L1 inhibitors have been proven effective in cancer therapy and have recently been approved by the US Food and Drug Administration (FDA), and have been successfully used to treat a variety of solid tumor types [6,7]. Carrelizumab is a PD-1/PD-L1 inhibitor independently developed in China. Since its introduction, it has attracted much industry attention and taken the international stage many times, and has been widely recognized in the field of oncology at home and abroad. Camrelizumab is a humanized IgG4κ-type anti-PD-1 monoclonal antibody that binds to PD-1 to block the PD-1/PD-L1 pathway, thereby activating T cells and producing sustained antitumor effects [8]. Since camrelizumab showed a good survival benefit in a singlearm phase II clinical trial of classical Hodgkin lymphoma, the drug was approved by the China Food and Drug Administration (CFDA) on May 29, 2019, for the treatment of relapsed or refractory classical Hodgkin lymphoma after at least second-line systemic chemotherapy [9]. Camrelizumab is also being studied for the treatment of various malignancies such as lung cancer, gastric cancer, nasopharyngeal carcinoma, as well as liver cancer [10].

We note that Reactive Cutaneous Capillary hyperplasia (RCCEP) appears to be a dermatological adverse event unique to camrelizumab treatment [11,12]. Even though dermatological adverse events are very common in PD-1/PD-L1 inhibitor drugs, RCCEP has not been reported in other PD-1/PD-L1 inhibitor treatments. The time to appearance of RCCEP after camrelizumab treatment is in the range of 20 to 42 d [12,13], with a significant dose dependence, and the shorter the time to appearance [12]. It is usually scattered throughout the body and can also be clustered, with the head and neck, trunk, and extremities being the most common parts [11,12]. Histopathologically, RCCEP showed clustered proliferation of thin-walled vessels in the dermis, vascular congestion and dilatation, and focal with a tendency to thrombosis [8]. The specific pathogenesis by which camrelizumab treatment leads to RCCEP is currently unknown. Some scholars Chen et al. [12] believe that this can be related to the imbalance between angiogenic contributors and inhibitors. Additional studies [14] have found that camrelizumab has off-target binding specificity, so it may promote angiogenesis and hemangioma formation by up-regulating Vascular Endothelial Growth Factor Receptor 2 (VEGFR2).

One phenomenon of interest is that there appears to be an association between RCCEP onset and higher response after camrelizumab treatment. In a previous single-arm multicenter phase II study of Song et al. [11] camrelizumab in relapsed or refractory classical Hodgkin’s lymphoma, 97.3% of patients developed RCCEP while achieving an Objective Response Rate (ORR) of 76.0%. A recent prospective phase I observational study [15] involving 98 patients with advanced solid tumors also found that after camrelizumab treatment, patients experienced grade 1-2 RCCEP, while signs of significant tumor regression were observed. However, whether RCCEP in camrelizumab treatment is associated with a higher shortterm response as well as long-term prognosis in patients has not been well characterized.

Because it acts by reactivating the antitumor T cell response, and hyperactivation of the immune system may contribute to a series of immune-related adverse events [5,16,17], such as RCCEP. It is, therefore, reasonable to assume that RCCEP onset may be a sign of a more robust immune antitumor response. In this study, we conducted a retrospective case-control study and assessed the relationship between RCCEP onset after camrelizumab treatment and multiple oncological outcomes, such as Objective Response Rate (ORR), Progression-Free Survival (PFS), and/or Overall Survival (OS), in patients with advanced solid tumors.

Material and Methods


A total of 92 patients with advanced solid tumors who developed RCCEP while receiving camrelizumab in our hospital between July 2019 and October 2020 were included in the study (RCCEP group). Inclusion criteria: 1) All patients developed RCCEP within 3 months after receiving camrelizumab treatment and were diagnosed by dermoscopy and tissue case examination; 2) Patients had complete treatment and follow-up data. Exclusion criteria: 1) Patients with a history of RCCEP at the time of treatment; 2) Patients with RCCEP due to other causes. Matched controls for RCCEP patients were based on age, gender, and camrelizumab treatment cycle, with a maximum of 5 controls matched for each case. And the control group were all patients who mentioned the onset of RCCEP after starting camrelizumab treatment until their progression was recorded.

Efficacy Assessments

Best overall response (BOR): Determine the best response data for patients treated with camrelizumab by manually examining patient cases. These include a Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). PD was defined as: (1) an increase of more than 20% in the diameter of a patient’s original tumor lesion and or the appearance of a new tumor lesion, and (2) the occurrence of death in a patient. Overall response rate (ORR) was defined as the percentage of patients with CR and PR. Disease control rate (DCR) was defined as the percentage of patients with CR, PR, and SD.

Progression-free survival (PFS): Is defined as the time interval from the start of treatment with camrelizumab to the occurrence of disease progression or death. Overall Survival (OS) was defined as the interval from the start of treatment with camrelizumab to the occurrence of death from any cause.

Statistical analysis

SPSS version 23.0 (SPSS, Inc., Chicago, IL, USA) software was applied for statistical analysis. Enumeration data were expressed as a case (percentage) [n (%)], Χ2 test or Fisher exact test was performed; patient age conformed to the normal distribution, expressed as mean ± standard deviation ( x ± s ), and independent sample t-test was used for comparison. Camrelizumab treatment weeks were expressed as median (range), and the Mann-Whitney U test was used for comparison. Kaplan-Meier curves for PFS in the two groups were plotted using GraphPad 7.0 and compared using the log-rank test; multivariate Cox regression analysis was used to evaluate factors influencing PFS in patients. The test level was α=0.05, and P<0.05 was considered statistically significant.


Baseline data of patients in the two groups

Of the 92 patients with advanced solid tumors treated with camrelizumab, 16 patients were eligible for the study. They were all diagnosed with RCCEP by dermoscopy and had no history of RCCEP in previous cases. Propensity matching was performed in the remaining patients according to age, gender, and timing of camrelizumab treatment, and 76 patients were included as a control group (none of the patients had RCCEP). The sociodemographic statistics and clinical data of the patients in the two groups are shown in Table 1. Only a few patients in both groups were treated with camrelizumab. Due to sample size limitations, not all cancer types were involved in the study. Among them, lung cancer and digestive tract tumors accounted for the majority (Table 2). Also, we noted a significant incidence of RCCEP for lung cancer (30.8% vs 7.7%) compared with digestive tract tumors (P=0.027).