Recurrence of Immune-Related Adverse Events After Immune Checkpoint Inhibitor Rechallenge—Reply

Abstract

To the Editor Recently, with the increasing research on immunerelated adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs), recurrence of irAEs after ICI rechallenge has deserved more attention. In their cohort study, Dolladille and colleagues 1 retrospectively assessed safety in patients with cancer who resumed therapy with the same ICIs and found that ICI rechallenge was associated with a recurrence of the same irAEs in one-quarter to one-third of the cases. However, there are some suggestions of this study that ought to be carefully considered, especially considering its promising research future as to ICIs.First, this study included patients with all kinds of cancers. But different varieties of cancers do not have similar rates of various irAEs. 2,3 Also, not all cancer types could achieve significant efficacy from ICIs, which means it is very important to evaluate the balance between the risk of irAEs and the efficacy of ICIs. 4 As a result, we suggest further exploration of between-study heterogeneity by subgrouping studies according to different cancer types. Second, this research compared the irAE rate between rechallenge and nonrechallenge cases but only reported the time to onset of initial irAEs, ignoring the time between recurrence of irAEs and ICI rechallenge, which is worthy of comparison. Third, this study evaluated the recurrence rate by dividing the number of cases with an irAE recurrence by the number of informative rechallenges. 1 However, they only included cases with a rechallenge with the same ICI drug after a first irAE, ignoring patients who had irAEs 2 or more times. Therefore, it is deficient to draw a conclusion from that calculation; it would be better regarded as a conditional conclusion. In closing, as to the suggestions enumerated above, further analysis is needed to obtain more valuable and rigorous conclusions.

Immune‐related adverse events in cancer patients being treated with immune checkpoint inhibitors

“…In contrast with prior findings suggesting that irAE recurrences tend to be easily managed, we found that 40% of irAE recurrences were high-grade, and nearly half occurred despite not being re-challenged with ICI therapy. [33][34][35][36][37] Finally, a considerable proportion of patients required subspecialty referral or hospitalization for irAE management. Our study highlights that irAE are clinically impactful and may contribute to further healthcare utilization, although this needs to be studied further.…”