Article Figures & Data
Figures
- Figure 1.
Features of patients in retreatment cohort. A, Rate of no (blue), recurrent (yellow), or new (yellow-striped) irAEs among patients retreated with immunotherapy after an initial irAE (n = 38). B, Box plots of time to retreatment of patients with recurrent/new (n = 20) or no irAEs (n = 18). The line in the boxes represents the median. Mann–Whitney test was used to compare the two groups and no difference was observed, P = 0.5. C, Rate of recurrent or new irAEs after retreatment. Labels over the top of the bars: number of patients. Fisher exact test P values refer to comparison of recurrent/new irAEs with no recurrent irAE. The significance threshold was set at a P ≤ 0.05. CR, complete response; SD: stable disease; PD: progressive disease.
- Figure 2.
Treatment exposure and response duration in the retreatment cohort. Colored solid bars: best objective response of each patient (n = 38). Stars, Objective response documented after retreatment. Arrow, Ongoing treatment; circle, retreatment date; triangle, first objective response.
- Figure 3.
Survival outcomes in lung cancer patients retreated with PD-1 blockade following an initial irAE. Kaplan–Meier curves of (A) PFS and (B) OS of patients in the retreatment (n = 26) and discontinuation cohorts (n = 22), who did not achieve partial or complete responses before the first irAE. Kaplan–Meier curve of (C) PFS and (D) OS of patients in the retreatment (n = 12) and discontinuation cohorts (n = 8), who achieved partial or complete responses before the first irAE. Differences between curves were statistically analyzed using the log-rank test. Significance threshold was set at a P ≤ 0.05. Censored patients are shown as vertical bars. The chart below the graphs represents the number of patients at risk.
Tables
- Table 1.
Characteristics of patients who experienced serious irAEs requiring treatment delay
Retreatment Discontinuation P No. of patients; N (%) 38 30 Median age, years (range) 64 (49–83) 66 (42–84) 0.59 Sex, female; N (%) 18 (47) 11 (37) 0.46 Smoking history, N (%) 0.51 Yes 33 (87) 24 (80) No 5 (13) 6 (20) Histology, N (%) 0.06 Adenocarcinoma 23 (61) 26 (87) Squamous 11 (29) 4 (13) LCNEC or NOS 4 (10) 0 (0) Immunotherapy treatment data, N (%) 0.18 Anti–PD-1 or Anti–PD-L1 24 (63) 24 (80) Combination w/anti–CTLA4 14 (37) 6 (20) Line of therapy, N (%) 0.007 First 25 (66) 9 (30) Second and beyond 13 (34) 21 (70) Best overall response, N (%) 0.62 CR or PR 18 (47) 12 (40) SD or PD 20 (53) 18 (60) Abbreviations: LCNEC, large-cell neuroendocrine cancer; NOS, not otherwise specified carcinoma; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; CTLA-4, cytotoxic T-lymphocyte–associated antigen 4; CR, complete response; SD, stable disease; PD, progressive disease.
- Table 2.
Characteristics of initial irAEs
Retreatment Discontinuation P Grade of the first irAE, N (%) 0.01 Grades 1 and 2 25 (66) 10 (33) Grades 3 and 4 13 (34) 20 (67) Type of irAE; N (%) 0.62a Pneumonitis 6 (16) 7 (23) Colitis 7 (18) 5 (17) Rash/pruritus 5 (13) 6 (20) ALT or AST increase 3 (8) 4 (13) Arthralgia/myalgia 5 (13) 1 (3) Nephritis 2 (5) 2 (7) Pancreatic enzymes elevation 4 (11) 0 (0) Meningitis/headache 2 (5) 1 (3) Endocrine disordersb 2 (5) 1 (3) Ventricular arrhythmias 1 (3) 0 (0) Fatigue 1 (2) 0 (0) ITP 0 (0) 1 (3) Other 0 (0) 2 (7) Hospitalizations, N (%) 8 (21) 16 (53) 0.01 Time interval to irAE: Days, median (range) 69 (14–577) 73 (2–452) 0.77 No. infusions before the irAE: No., median (range) 4.5 (1–42) 5.5 (1–27) 0.51 Corticosteroid used, N (%) 29 (76) 29 (97) 0.03 Intravenous 3 (10) 12 (40) Oral 23 (80) 16 (53) Otherc 3 (10) 2 (6) Steroids > 4 weeks, N (%) 10 (34) 15 (65)d 0.04 Anti-TNF used in the first toxicity, N (%) 0 (0) 3 (9) 0.05 irAE resolved to, N (%) 0.03 Grades 0 and 1 37 (97) 23 (79) Grade ≥ 2 1 (3) 6 (21) Death related to irAE; N (%) 0 2 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ITP, idiopathic thrombocytopenic purpura; Anti-TNF, antitumor necrosis factor alpha.
↵aThis P value refers to the comparison of the four more common toxicities.
↵bHypothyroidism (n = 1), hyperthyroidism (n = 1), and adrenal insufficiency (n = 1).
↵cTopical steroids or nonabsorbable budesonide.
↵dThere are 6 patients who were not evaluable for this category for reasons such as death, loss of follow-up, and noncompliance.
Supplementary Data
- Supplemental Figure 1 - Time From First Dose of Immunotherapy to Date of The Initial irAE
- Supplemental Figure 2 - Overall Survival for Patients in the Retreatment Cohort
- Supplemental Table 1 - Patients with Advanced NSCLC Treated at MSKCC with Immunotherapy From April 2011 to May 2016
- Supplemental Table 2 - Retreatment Cohort - Initial irAEs: Clinical Characteristics and Features
- Supplemental Table 3 - Retreatment Cohort - Recurrent irAEs: Characteristics of The Recurrent Immune-Related Toxicity
Volume 6, Issue 9
