Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma

Abstract

Patients who discontinued CTLA-4/PD-1 blockade for severe irAEs had relatively high rates of recurrent or distinct toxicities with anti-PD-1 resumption. However, many patients, particularly with combination-induced colitis, tolerated anti-PD-1 rechallenge well, and this approach can be considered in selected patients.

A review of cancer immunotherapy toxicity

“…In a retrospective cohort study that included 93 patients who had multiple tumor types and prior grade ≥2 irAEs with combination or anti–PD‐1/anti–PD‐L1 monotherapy, 17 of 40 patients who were rechallenged with anti–PD‐1/anti–PD‐L1 developed a recurrent irAE, and 5 patients developed a de novo irAE . A multicenter, retrospective analysis that included 80 patients with melanoma who were rechallenged with anti–PD‐1 therapy after experiencing an irAE with combination therapy reported recurrence of the irAE in 18% of patients and development of a de novo irAE in 21% . One grade 5 recurrence occurred in a patient who had had grade 2 rash with combination therapy and developed SJS/TEN with anti–PD‐1.…”

“…103 A multicenter, retrospective analysis that included 80 patients with melanoma who were rechallenged with anti-PD-1 therapy after experiencing an irAE with combination therapy reported recurrence of the irAE in 18% of patients and development of a de novo irAE in 21%. 104 One grade 5 recurrence occurred in a patient who had had grade 2 rash with combination therapy and developed SJS/TEN with anti-PD-1. The variation in the rate of irAEs with rechallenge observed in these 2 studies may reflect differences in the initial immunotherapy leading to irAE, because patients in the study by Pollack et al transitioned from combination therapy to anti-PD-1 monotherapy, which has a lower overall toxicity profile, whereas many of the patients in the study by Simonaggio et al developed the initial irAE on anti-PD-/1PD-L1 monotherapy and were later rechallenged with the same class of therapy.…”

“…The variation in the rate of irAEs with rechallenge observed in these 2 studies may reflect differences in the initial immunotherapy leading to irAE, because patients in the study by Pollack et al transitioned from combination therapy to anti-PD-1 monotherapy, which has a lower overall toxicity profile, whereas many of the patients in the study by Simonaggio et al developed the initial irAE on anti-PD-/1PD-L1 monotherapy and were later rechallenged with the same class of therapy. Studies have shown that patients with severe irAEs during combination therapy have high response rates and good clinical outcomes with observation alone, 104 and guidelines recommend the consideration of close surveillance in patients with responding or stable disease. 5 Patients with preexisting autoimmune disease or prior irAEs encompass a diverse spectrum of disease pathophysiology and severity, and long-term prospective studies are needed to clarify the optimal approach to ICI therapy in specific clinical scenarios.…”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…Therefore, new effective antitumor treatments should be urgently developed. [9][10][11][12] Therefore, one considerable strategy is to improve the efficacy of immunotherapeutic drugs and reduce their side effects. For example, the success of immune checkpoint inhibitors, such as antiprogrammed death (PD-1)/programmed death-ligand 1 (PD-L1) and anticytotoxic T lymphocyte-associate antigen-4 (anti-CTLA-4) antibodies, have substantially promoted the development of oncology treatments.…”

“…8 Moreover, immune side effects, including the cascade effect of inflammatory mediators, hematopoietic system dysfunction, organ toxicity and rapid emergence of drug resistance, have limited the clinical optimization of these methods. [9][10][11][12] Therefore, one considerable strategy is to improve the efficacy of immunotherapeutic drugs and reduce their side effects.…”