Treatment strategies and safety of rechallenge in the setting of immune checkpoint inhibitors-related myositis: a national multicentre study

Abstract

Objectives The occurrence of immune-related myositis (irM) is increasing, yet there are no therapeutic guidelines. We sought to analyze the current therapeutic strategies of irM and evaluate the outcomes of immune checkpoint inhibitors (ICI) rechallenge. Methods We conducted a nationwide retrospective study between April 2018 and March 2020 including irM without myocardial involvement. Depending on the presence of cutaneous signs or unusual histopathological features, patients were classified into two groups: typical or atypical irM. Therapeutic strategies were analyzed in both groups. The modalities and outcomes of ICI rechallenge were reviewed. Results Among the 20 patients, 16 presented typical irM. Regardless of severity, most typical irM were treated with steroid monotherapy (n = 14/16) and all had a complete response within ≤ 3 weeks. The efficacy of oral steroids for non-severe typical irM (n = 10) was the same with low-dose (≤ 0.5 mg/kg/day) or high-dose (1 mg/kg/day). Severe typical irM were successfully treated with intravenous methylprednisolone. Atypical irM (n = 4) had a less favorable evolution, including one irM-related death, and required heavy immunosuppression. ICI were safely reintroduced in 9 patients presenting a moderate (n = 6) or a severe (n = 3) irM. Conclusion Our data highlight that steroid monotherapy is an effective treatment for typical irM, either with prednisone or with intravenous methylprednisone pulses depending on the severity. The identification of unusual features is important in determining the initial therapeutic strategy. The outcomes of rechallenged patients are in favor of a safe reintroduction of ICI following symptom resolution and CK normalization in moderate and severe forms of irM.

Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review

“…Studies having specifically assessed the safety of ICI retreatment after ICI discontinuation for irAEs remain scarce and heterogenous. Most are based on small samples of patients [ 18 , 19 , 20 ] or focused only on the recurrence rate of the same irAE after an ICI rechallenge [ 21 ]. Moreover, patients with grade ≥3 irAEs have been excluded from many of these studies [ 22 , 23 , 24 , 25 ].…”

Immune Checkpoint Inhibitor–Associated Myositis

“…Four of 5 patients did not have a flare, whereas one had recurrent MG and myositis with respiratory failure and recovered 15 . In a more recent case series, 9 patients (2 severe) with isolated ICI myositis were rechallenged with ICI within 4 months of the ICI myositis occurrence, and none of these patients experienced relapse of myositis at median follow-up of 457 days 36 . Interestingly, 6 of 9 patients were given steroids preemptively for approximately 3 months (10–50 mg prednisone daily).…”

“…Necrosis can range from multifocal clusters to diffuse confluent areas with myophagocytosis and regenerating fibers 9,10,14,23 . Atrophic muscle fibers are usually scattered and intermixed; however, there are also reports of perifascicular predominant distribution 10,36 . Strong MHC-1 staining is reported especially in degenerating muscle fibers 14,23 .…”

“…15 In a more recent case series, 9 patients (2 severe) with isolated ICI myositis were rechallenged with ICI within 4 months of the ICI myositis occurrence, and none of these patients experienced relapse of myositis at median followup of 457 days. 36 Interestingly, 6 of 9 patients were given steroids preemptively for approximately 3 months (10-50 mg prednisone daily). Regardless of steroid administration, none of the patients experienced relapse of myositis at follow-up.…”

Immune checkpoint inhibitor-related myositis: from pathophysiology to treatment

“…Weill et al reported that none of the 9 patients in their national multicentre study that were rechallenged with ICIs had a relapse of myositis, though one patient developed immune-related colitis. Of note, none of the patients in the study had myocardial involvement, and some patients were excluded from rechallenge due to severity and safety reasons (61). Hence, ICI rechallenge appears to be a potentially feasible option after deliberation between the muscle and cancer specialist and the patient with careful consideration of the clinical presentation and severity of disease.…”