Causes of Pruritus in Patients Treated With Immune Checkpoint Inhibitors for Melanomas or Skin Carcinomas

Abstract

Background: Pruritus is a frequent adverse event during the use of immune checkpoint inhibitors (ICIs), with a frequency estimated to be between 11 and 47%. The underlying causes remain poorly understood.Objectives: The main goal was to search for putative causes of pruritus occurring in patients treated with ICIs for melanomas and cutaneous carcinomas. Other objectives were to assess the association between the occurrence of pruritus and survival and between the occurrence of pruritus and other adverse events.Methods: A monocentric retrospective descriptive study was performed using data for patients treated with ICIs (nivolumab, pembrolizumab, ipilimumab, and cemiplimab) between August 2010 and November 2019.Results: A total of 181 patients were included (mean age: 69 years). Pruritus was reported by 25 patients (13.8%). We were able to determine three subgroups of pruritus causes under ICI use: pruritus directly related to immunotherapy, pruritus indirectly related through other pruritus-inducing side effects and pruritus unrelated to ICIs. In 6/25 patients, no more specific cause of pruritus was found at the onset of pruritus or in their backgrounds, other than ICI use.Limitations: The study has some limitations due to unicentric and retrospective design.Conclusion: Pruritus was found in 25/181 patients in this series; only in 6/25 patients no potential cause other than ICI could be found, and pruritus was not associated with differences in survival.

Drawbacks of Immune Checkpoint Inhibition and Rigorous Management for Immune Related Adverse Events Along with a Strategy Against Tumor Plasticity

“…One has to be very careful by presenting the onset frequency of irAEs, as the numbers vary widely in the literature each based on different study models with their own limitations [15][16][17][18][19][20][21][22][23][24][25][26][27].…”

“…It shall be noted that by presenting the approximate onset frequency for irAEs in The same is going to be valid for the next two tables, in which I will present approximate timing of some selected irAEs and related CTCAE grading peak in monotherapy and combination therapy applications, and approximate onset frequency of irAEs with respect to organ/tissue systems in a CTLA-4/PD-1 combination therapy scenario, respectively. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. In Table 3, again the weeks refer to weeks after the initial infusion and the damping time is as explained for Table 2 above.…”

Drawbacks of Immune Checkpoint Inhibition and Rigorous Management for Immune Related Adverse Events Along with a Strategy Against Tumor Plasticity

“…One has to be very careful by presenting the onset frequency of irAEs, as the numbers vary widely in the literature each based on different study models with their own limitations [15][16][17][18][19][20][21][22][23][24][25][26][27]. Apart from this, as also stated above, combination therapy yields 3 of 28 different frequency, timing and risk duration results compared to ICIT applied as monotherapy.…”

“…The same is going to be valid for the next two tables, in which I will present approximate timing of some selected irAEs and related CTCAE grading peak in monotherapy and combination therapy applications, and approximate onset frequency of irAEs with respect to organ/tissue systems in a CTLA-4/PD-1 combination therapy scenario, respectively. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Please note that the weeks in Table 2 refer to weeks after the initial infusion.…”

Drawbacks of Immune Checkpoint Inhibition and Rigorous Management for Immune Related Adverse Events Along with a Mathematical Model to Assess Therapy Success and Optimum Therapy Duration and a Strategy Against Tumor Plasticity

“…The same is going to be valid for the next two tables, in which I will present approximate timing of some selected irAEs and related CTCAE grading peak in monotherapy and combination therapy applications, and approximate onset frequency of irAEs with respect to organ/tissue systems in a CTLA-4/PD-1 combination therapy scenario, respectively. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. PD-1: Programmed cell death protein 1…”