Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society.

BACKGROUND: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk. OBJECTIVE: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS). METHODS: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal. RESULTS: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations. CONCLUSION: These recommendations propose a strategic approach to managing cancer risk in PwMS.

Pharmacokinetics and pharmacodynamics of antibody-drug conjugates for the treatment of patients with breast cancer.

INTRODUCTION: Currently three antibody-drug-conjugates (ADC) are approved by the European Medicines Agency (EMA) for treatment of breast cancer (BC) patient: trastuzumab-emtansine, trastuzumab-deruxtecan and sacituzumab-govitecan. ADC are composed of a monoclonal antibody (mAb) targeting a specific antigen, a cytotoxic payload and a linker. Pharmacokinetics (PK) and pharmacodynamics (PD) distinguish ADC from conventional chemotherapy and must be understood by clinicians. AREAS COVERED: Our review delineates the PK/PD profiles of ADC approved for the treatment of BC with insight for future development. This is an expert opinion literature review based on the EMA's Assessment Reports, enriched by a comprehensive literature search performed on Medline in August 2023. EXPERT OPINION: All three ADC distributions are described by a two-compartment structure: tissue and serum. Payload concentration peak is immediate but remains at low concentration. The distribution varied for all ADC only with body weight. mAb will be metabolised firstly by the saturable complex formation of ADC/Tumour-Receptor and secondly by binding of FcgRs in immune cells. They are all excreted in the bile and faeces with minimal urine elimination. Dose adjustments, apart from weight, are not recommended. Novel ADC are composed of cleavable linkers with various targets/payloads with the same PK/PD properties, but novel structures of ADC are in development.

Arterial hypertension associated with PARPi: A meta-analysis of 41 placebo randomized controlled trials combined with a World Health Organization's pharmacovigilance study.

BACKGROUND: Arterial hypertension has been recently reported from randomized controlled trials (RCTs) assessing poly (ADP-ribose) polymerase inhibitor (PARPi). OBJECTIVE: In a context of increasing use of PARPi, it is crucial to properly assess risk and incidence of this adverse event for clinical practice. METHODS: We performed a systematic review and meta-analysis in MEDLINE, Cochrane CENTRAL and ClinicalTrials.gov up to January 4, 2023 with an ongoing surveillance up to June 7, 2023. RCTs comparing PARPi to placebo in adult patients with solid tumors were included if hypertension was reported. The primary outcome was the summary risk ratio (RR, with 95% CIs) of any hypertension of PARPi class in placebo RCTs. Secondary outcomes were the summary risk and incidence of hypertension of each individual PARPi. To provide clinical features of PARPi-associated hypertension, we independently queried the WHO's pharmacovigilance database, up to September 1, 2022. RESULTS: In total, 41 placebo RCTs (n = 15 264 adult patients) were included. PARPi class was not associated with an increased risk of hypertension compared with placebo. In individual analyses, the risk of hypertension was lower with olaparib than placebo (RR 0.77 [95% CI: 0.68-0.86], P < 0.01; I2  = 19%, χ2 P = 0.26). Niraparib monotherapy increased the risk of any (RR 2.84 [95% CI: 1.76-4.57], P < 0.01; I2  = 66%, χ2 P = 0.01) hypertension with a summary incidence of 19.87% (95% CI: 15.23-25.50). In real-life setting, niraparib-associated hypertension occurs within 20 days and was serious in 66%. Co-prescription of at least one antihypertensive or therapy-induced hypertension was reported in 20.5% or 14.4% of cases, respectively. CONCLUSIONS: In a context of extensive assessment of niraparib in combination, these data reinforce the need of a close monitoring of this adverse event to preserve its clinical benefit on patients' survival.

Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization's database.

Importance: Endocrine therapies (ETs) and inhibitors of cyclin-dependent kinases-4/6 (iCDK4/6s) are a standard treatment in breast cancer. However, data on potential neurocognitive impacts remain inconsistent for ET and are scarce for iCDK4/6s. Objective: To evaluate whether ET and iCDK4/6s are associated with neurocognitive impairment (NCI). Methods: We used observational, real-world cases of NCI from the World Health Organization's database VigiBase® to perform disproportionality analysis. Cases were defined as any symptom of NCI in females treated with ETs or iCDK4/6s. The study period was from the date of the first adverse event reported in VigiBase® with iCDK4/6s (1 January 2014) until the date of data extraction (16 March 2022). In our primary analysis, we calculated the reporting odds ratio (ROR) adjusted for age to identify a potential association between NCI and individual ETs in isolation or in combination with iCDK4/6s. We also performed subgroup analyses by the NCI class. Results: We identified 2.582 and 1.943 reports of NCI associated with ETs and iCDK4/6s, respectively. NCI was significantly associated with each ET [anastrozole: n = 405, aROR = 1.52 (95% CI: 1.37-1.67); letrozole: n = 741, aROR = 1.37 (95% CI: 1.27-1.47); exemestane: n = 316, aROR = 1.37 (95% CI: 1.22-1.53); tamoxifen: n = 311, aROR = 1.25 (95% CI: 1.12-1.40); and fulvestrant: n = 319, aROR = 1.19 (95% CI: 1.06-1.33)] and only with palbociclib for iCDK4/6s [n = 1,542, aROR = 1.41 (95% CI: 1.34-1.48)]. Conclusion: These findings suggest that in females treated for breast cancer, all ETs may be associated with NCI. However, amongst iCDK4/6s, NCI may be specific to palbociclib. NCI most frequently involved learning and memory as well as language. Neurocognitive impact of treatments requires better consideration and management.

Infections associated with clozapine: a pharmacovigilance study using VigiBase®.

Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase® to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dose-dependency, and to investigate the underlying mechanism. Methods: Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose-effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. Results: A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41-0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; p < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; p < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug-drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Discussion: Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The co-administration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial.

Does COVID-19 pandemic impact cancer outcomes in metastatic setting? A comparative cohort study among metastatic patients treated at day care hospital.

INTRODUCTION: COVID-19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes. METHODS: We conducted a retrospective comparative cohort study to assess the impact of the COVID-19 outbreak in 2020 on cancer outcomes in metastatic patients. Two cohorts of metastatic patients receiving intravenous (iv) therapy in a French oncological day care hospital were assessed: a 2020 cohort during the first French lockdown, and a 2018 historical cohort before the COVID-19 pandemic. We performed a propensity score analysis to match patients from the two cohorts. After one-year follow-up, we compared progression-free survival (PFS) and overall survival (OS) between cohorts. Adaptations of medical oncological treatments in 2020 were also analysed. RESULTS: The 376 patients of the 2020 cohort were matched with 376 of the 2018 cohort. No SARS-CoV-2 infection was observed in the 2020 cohort. The adjusted PFS was significantly shorter in 2020 compared to 2018 (HR = 1.23; 95% CI: 1.03-1.46), as well as among patients without treatment adaptation compared to matched patients of the 2018 cohort (HR = 1.33; 95% CI: 1.10-1.61). We did not observe any significant difference of PFS among the group with treatment adaptations. OS was not significantly different. CONCLUSION: Metastatic cancer patients treated during the first lockdown had a higher risk of disease progression 1 year after COVID-19 outbreak. However, oncological treatment adaptations or SARS-CoV-2 infections do not explain these results. A longer follow-up is needed to observe the impact on OS.

Atrial Fibrillation Incidence Associated With Exposure to Anticancer Drugs Used as Monotherapy in Clinical Trials.

Background: The incidence of atrial fibrillation (AF) associated with anticancer drugs in cancer patients remains incompletely defined. Objectives: The primary outcome was the annualized incidence rate of AF reporting associated with exposure to 1 of 19 anticancer drugs used as monotherapy in clinical trials. The authors also report the annualized incidence rate of AF reported in the placebo arms of these trials. Methods: The authors systematically searched ClinicalTrials.gov for phase 2 and 3 cancer trials studying 19 different anticancer drugs of interest used as monotherapy, up to September 18, 2020. The authors performed a random-effects meta-analysis to compute summary AF annualized incidence rate with its 95% CI using log transformation and inverse variance weighting. Results: A total of 191 clinical trials (47.1% were randomized) of 16 anticancer drugs across 26,604 patients were included. Incidence rates could be calculated for 15 drugs administered singly as monotherapy. Summary annualized incidence rates of AF reporting associated with exposure to 1 of the 15 anticancer drugs used as monotherapy were derived; these ranged from 0.26 to 4.92 per 100 person-years. The 3 highest annualized incidence rates of AF reporting were found for ibrutinib 4.92 (95% CI: 2.91-8.31), clofarabine 2.38 (95% CI: 0.66-8.55), and ponatinib 2.35 (95% CI: 1.78-3.12) per 100 person-years. Summary annualized incidence rate of AF reporting in the placebo arms was 0.25 per 100 person-years (95% CI: 0.10-0.65). Conclusions: AF reporting is not a rare event associated with anticancer drugs in clinical trials. A systematic and standardized AF detection should be considered in oncological trials, particularly those studying anticancer drugs associated with high AF rates. (Incidence of atrial fibrillation associated with anticancer drugs exposure in monotherapy, A safety meta-analysis of phase 2 and 3 clinical trials; CRD42020223710).

How to improve adherence of guidelines for localized testicular cancer surveillance: A Delphi consensus study.

Stage-I testicular germ-cell tumor (TGCT) has excellent cure rates. Surveillance is fully included in patient's management, particularly during the first years of follow-up. Surveillance guidelines differ between the academic societies, mainly concerning imaging frequency and long-term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. First, an online survey on surveillance practice of stage-I TGCT based on clinical-cases was conducted among urologists, radiation-oncologists and medical-oncologists. These results were compared to ESMO/EAU and AFU guidelines. Then a panel of experts assessed surveillance proposals following a Delphi-CM. Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. The study was conducted between July 2018 and May 2019. Concerning the first step: 61 participated to the survey (69% medical-oncologists, 15% urologists, 16% radiation-oncologists). About 65% of practitioners followed clinico-biological guidelines concerning 1 to 5 years of follow-up, but only 25% stopped surveillance after the 5th-year. No physician followed the EAU/ESMO guidelines of de-escalation chest imaging. Concerning the second step: 32 experts (78% medical-oncologists, 16% urologists, 6% radiation-oncologists) participated to the Delphi-CM. Thanks to Delphi-CM, a consensus was reached for 26 of the 38 statements. Experts agreed on clinico-biological surveillance modalities and end of surveillance after the 5th-year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th-year of follow-up. No consensus was reached regarding de-escalation of chest imaging. To conclude, the survey proved that French TGCT-specialists do not follow current guidelines. With Delphi-CM, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th-year, stop of AP scan on the 4th-year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging.

HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer.

BACKGROUND: HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification). METHODS: We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed. RESULTS: We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15-0.84] and HR = 0.24 [0.07-0.81], respectively). NLR was not associated with worse DFS or OS. CONCLUSION: In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors.

Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the impact of NLR on survival in mBC patients treated with first line CdK4/6i. Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. The biomarker threshold was defined using ROC curves. We analyzed progression free survival (PFS), overall survival (OS), 12-month PFS and response rate according to NLR in univariable and multivariable analysis. Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 33 months [range: 2.9-57]. Median age was 65 years [29-86], 40% patients had good performance status (ECOG-PS 0). Most patients (71%) were included at the metastatic relapse stage and 29% had only bone metastases. Median PFS and median OS were 27 and 51 months, respectively. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.50, CI95% = [0.32-0.79]) and worse OS (HR=0.45, [CI95%: 0.23-0.87]). In multivariable analysis, NLR and ECOG PS were independently factors associated with PFS (p=0.016 and p=0.001, respectively). Conclusion: High NLR was associated with worse PFS and OS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could help optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

Baseline lymphopenia as prognostic factor in patients with metastatic breast cancer treated with palbociclib.

Cyclin-dependent-kinase 4-6 inhibitors (CDK4/6i) have improved the management of hormone receptor (HR)+/human epidermal growth factor receptor (HER)2- metastatic breast cancer (mBC). Currently, there are no valid prognostic factors for response to CDK4/6i. Baseline lymphopenia is reported as a prognostic factor in several types of cancer. The present retrospective study aimed to evaluate the effect of baseline absolute lymphocyte count (ALC) on response to palbociclib. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival (OS), best response and safety. A total of 114 patients treated for mBC between 2016 and 2019 were included. Median baseline ALC was 1.4 g/l (range, 0.2-4.3 g/l). A total of 65 (57%) and 49 (43%) patients had baseline ALC values of <1.5 and ≥1.5 g/l, respectively. Patients with baseline lymphopenia exhibited significantly shorter PFS (6 vs. 10 months; P=0.004) and OS (20 vs. 33 months; P=0.02). ALC <1.5 g/l independently predicted worse survival, as indicated by multivariate analysis (P=0.04; hazard ratio, 1.76; 95% confidence interval, 1.02-3.02). Patients with baseline ALC <1.5 g/l had significantly less partial response (14 vs. 22%; P=0.016) and more disease progression (46 vs. 20%; P=0.016) than those with ALC ≥1.5 g/l. ALC is a strong and easy-to-use dosage with prognostic factor for patients with HR+/HER2- mBC treated with palbociclib and endocrine therapy. Lymphopenia may also be a predictive factor of early progression. These data need to be verified in a larger prospective study.

Cardiovascular immunotoxicities associated with immune checkpoint inhibitors: a safety meta-analysis.

AIMS: The risk and incidence of cardiovascular (CV) immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in cancer patients remain unknown. METHODS AND RESULTS: We systematically reviewed all randomized clinical trials (RCTs) including at least one ICI-containing arm and available CV adverse event (CVAE) data in cancer patients in the ClinicalTrials.gov registry, Medline, and the Cochrane CENTRAL Register of Controlled Trials, up to 31 August 2020 (CRD42020165672). The primary outcome was the summary risk of 16 different CVAEs associated with ICI exposure vs. controls (placebo and non-placebo) in RCTs. CVAEs with an increased risk associated with ICI exposure were considered as CV irAEs. Summary incidences of CV irAEs identified in our primary outcome analyses were computed using all RCTs including at least one ICI-containing arm. We used a random-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% confidence intervals (CIs) and logit transformation and inverse variance weighting to compute summary incidences. Sixty-three unique RCTs with at least one ICI-containing arm (32 518 patients) were retrieved, among which 48 (29 592 patients) had a control arm. Among the 16 CVAEs studied, ICI use was associated with an increased risk of 6 CV irAEs including myocarditis, pericardial diseases, heart failure, dyslipidemia, myocardial infarction, and cerebral arterial ischaemia with higher risks for myocarditis (Peto OR: 4.42, 95% CI: 1.56-12.50, P < 0.01; I2 = 0%, P = 0.93) and dyslipidemia (Peto OR: 3.68, 95% CI: 1.89-7.19, P < 0.01; I2 = 0%, P = 0.66). The incidence of these CVAEs ranged from 3.2 (95% CI 2.0-5.1) to 19.3 (6.7-54.1) per 1000 patients, in studies with a median follow-up ranging from 3.2 to 32.8 months. CONCLUSION: In RCTs, ICI use was associated with six CV irAEs, not confined to myocarditis and pericarditis.

Efficacy and Safety of Weekly Paclitaxel in Breast Cancer With Symptomatic Bone Marrow Infiltration.

BACKGROUND/AIM: Currently, there is no recommendation for the treatment of breast cancer (BC) with bone-marrow cell infiltration (BMI). We evaluated the efficacy and safety of weekly-paclitaxel in this population. PATIENTS AND METHODS: This retrospective study included all BC patients with BMI receiving weekly-paclitaxel between January 2014 and May 2018. Overall-survival (OS) was the primary endpoint. Secondary endpoints were progression-free-survival (PFS) and safety. RESULTS: BMI was diagnosed in 26 patients. This infiltration was suggested by peripheral blood smear in 73% of cases. All patients had anemia, and 77% had thrombocytopenia. OS and PFS were 7.2 months [95% confidence interval (CI)=2.6-20.7] and 3.3 months (95%CI=1.6-7.2), respectively. Good performance-status, absence of thrombocytopenia and presence of less than 5% of circulating erythroblasts at BMI diagnosis, were associated with better survival. One patient presented grade 5 febrile neutropenia but no episodes of bleeding were reported. CONCLUSION: Weekly-paclitaxel is an effective therapeutic option with limited toxicity for BC with BMI.

Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer.

Importance: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE). Objective: To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences. Design, Setting, and Participants: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included. Main Outcomes and Measures: The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge. Results: A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs. Conclusions and Relevance: This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.