# Polymyalgia Rheumatica (PMR) and Polymyalgia Rheumatica-like (PMR-like) Manifestations in Cancer Patients Following Treatment with Nivolumab and Pembrolizumab: Methodological Blurred Points Identified Through a Systematic Review of Published Case Reports

## TL;DR

This paper reviews case reports of cancer patients developing polymyalgia rheumatica (PMR) after treatment with nivolumab or pembrolizumab, highlighting inconsistencies in how these cases are diagnosed and classified.

## Contribution

The study identifies methodological inconsistencies in diagnosing PMR following ICI therapy, particularly in the use of standardized criteria and ADR assessment tools.

## Key findings

- Most case reports did not use validated scales like Naranjo’s for adverse drug reaction assessment.
- Nivolumab cases often used validated PMR criteria, while pembrolizumab cases relied on clinical judgment.
- PMR symptoms occurred within 1 to 14 cycles of treatment, aligning with drug pharmacokinetics.

## Abstract

Background: Among rheumatologic diseases following therapy with immune checkpoint inhibitors (ICIs), the cases of cancer patients diagnosed as having polymyalgia rheumatica (PMR), particularly with nivolumab and pembrolizumab, has been steadily rising in published reports. Objectives: We performed a systematic review of published case reports with the aim of answering these questions: (1) Is PMR following therapy with nivolumab and pembrolizumab an adverse drug reaction (ADR)? (2) Is there a difference between cases of PMR following therapy with nivolumab and those following therapy with pembrolizumab? Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search in three main bibliographic databases: MEDLINE (Ovid interface), EMBASE, and COCHRANE Library was carried out on 27 December 2024. This systematic review has no registration number. Results: Data were extracted from 12 patients. Namely, 5 cases followed treatment with nivolumab and 7 with pembrolizumab. Validated scales for ADR assessment—such as Naranjo’s scale—were not used in 10 out of the 12 patients. Additionally, validated diagnostic or classification criteria for PMR were used in the majority of case reports related to nivolumab. On the contrary, clinical judgment alone was the rule in almost all case reports on pembrolizumab. Finally, the time interval between PMR manifestations and nivolumab/pembrolizumab therapy ranged from one to 14 cycles (fully compatible with pharmacokinetics). Conclusions: Our literature review highlighted significant methodological blurred lines in the categorization of PMR following therapy with nivolumab or pembrolizumab.