| The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage. |
According to results of an observational study, nearly half of “real-world” patients developing a rheumatologic immune-related adverse event (irAE) while undergoing treatment with an immune checkpoint inhibitor (ICI) were able to continue ICI treatment without interruption. These findings were presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.1
In this presentation, Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg, Germany, described the rationale for, and characteristics of, a registry of real-world patients with cancer who exhibit symptoms of rheumatic disease.
With patient recruitment initiated at the University of Heidelberg in 2018, the MalheuR project (Malignancies and rheumatic diseases) was described as “an open-label, nonrandomized, retro- and prospective, noninterventional observational study” with a focus on gaining understanding of the inter-relationships between malignant and rheumatic diseases and facilitating the development of standardized guidelines to manage both of these disease processes.
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Dr Benesova explained that the MalheuR project has 3 dimensions, each of which represents a “possible context of coincidence between malignant and rheumatic diseases”:
- Patients with classical rheumatic diseases that have a history of malignancy (RheuMal arm of the study)
- Patients with therapy-induced rheumatic symptoms due to antineoplastic therapy (TRheuMa arm of the study)
- Patients with malignancy who exhibit paraneoplastic rheumatic symptoms in (ParaRheuMa arm of the study).
With 550 patients enrolled in the registry after 2 years, this presentation focused on the 77 patients in the TRheuMa arm. Of these patients, 65 were undergoing treatment with ICI therapy, and 38%, 33%, and 17% were classified as having a diagnosis of non-small cell lung cancer (NSCLC), melanoma, and other malignancy, respectively.
A key approach to facilitating a better understanding of underlying disease processes is the further classification of patients treated with ICI therapy according to the pattern of rheumatic disease that their irAEs resemble.
Thus far, 39% of patients have exhibited irAEs represented by an asymmetric spondyloarthritis/psoriatic arthritis-like pattern, 20% of patients have irAEs characterized by a symmetrical pattern that mostly involve small joints, such as rheumatoid arthritis, and 14% of patients had irAEs resembling polymyalgia rheumatic-like disease, such as symmetrical myalgia of the shoulder and hip girdle.
“Also, a growing number of patients with preexisting [rheumatic disease] experience a flare of their disease as an irAE,” reported Dr Benesova.
Regarding laboratory parameters, specific findings were reported to be rare, with the presence of autoantibodies mostly absent, although approximately three-quarters of patients had elevated C-reactive protein (CRP) levels. Of note, pathologic arthrosonographic findings were observed 49 of 51 patients evaluated with this method.
In reviewing a previously published therapeutic algorithm for rheumatic irAEs developed in collaboration with oncologists,2 Dr Benesova described how mild-to-moderate rheumatic irAEs, like tendinitis and arthritis, usually respond well to low-dose prednisolone up to 10 mg, NSAIDS, or combination of both.
She also noted that while oncologists usually discontinue ICIs at oral prednisolone levels above 10 mg, such treatment allows for continuation of ICI therapy.
“From our experience, rheumatic irAEs respond better to low-dose prednisone than classical [rheumatological diseases],” she commented.
The presence of more severe symptoms or organ manifestations typically necessitates high-dose oral prednisolone up to 1 mg/kg daily, and ICIs are withheld. Finally, life-threatening rheumatic irAEs such as severe myositis, while very rare, necessitate treatment with intravenous prednisolone up to 2 mg/kg daily and permanent discontinuation of ICI therapy.
Of the 65 patients receiving ICI therapy, rheumatic irAEs were sufficiently managed with steroids up to 10 mg daily with or without NSAIDS in 42%; ICI discontinuation was necessary in only 15% of patients.
Regarding oncologic outcomes for the patients with melanoma (25 individuals), a complete response (CR) was achieved in 48%, which was longstanding in most patients. For those with a diagnosis of NSCLC (29 individuals), no patient achieved a CR, but a partial response was observed in 69% of patients, with duration of response still under investigation.
In her concluding remarks, Dr Benesova stated that “rheumatic irAEs are mostly not severe, well verifiable by imaging and CRP (seldom by autoantibodies), mostly well treatable, and associated with a better oncologic outcome.”
Disclosure: Some of the authors of the study reported financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.
References
- Benesova K, Diekmann L, Lorenz H-M, et al. TRheuMa registry provides real world data on rheumatic immune-related adverse events. Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 1809O.
- Benesova K, Lorenz H-M, Leipe J, Jordan K. How I treat cancer: treatment of rheumatological side effects of immunotherapy. ESMO Open. 2019;4:e000529. doi:10.1136/esmoopen-2019-000529
