Immune checkpoint inhibitor-related neurotoxicity: Incidence and management. A systematic review and meta-analysis.

Atypical Antiglomerular Basement Membrane Nephritis Following Immune Checkpoint Inhibitor

Immune-Related Adverse Events and Outcomes in Patients with Advanced Non–Small Cell Lung Cancer: A Predictive Marker of Efficacy?

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors.

Mending Broken Hearts

Immune checkpoint inhibitors (ICIs) have improved survival in patients with advanced melanoma but can be associated with a spectrum of immune-related adverse events (AEs), including both autoimmune-related AEs and other immune-related inflammatory AEs. These associations have primarily been evaluated in clinical trials that include highly selected patients, with older adults often underrepresented. To evaluate the association between use of ICIs and immune-related AEs (autoimmune and other immune related) among older patients with cutaneous melanoma. A population-based cohort study was conducted from January 1, 2011, to December 31, 2015. Data were analyzed from January 31 to May 31, 2021. With use of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries, patients of White race diagnosed with stages II-IV or unknown (American Joint Committee on Cancer, AJCC Cancer Staging Manual 6th edition) first primary cutaneous melanoma during 2011-2015, as reported to SEER, and followed up through December 31, 2015, were identified. Immune checkpoint inhibitors for treatment of melanoma. The association between ICIs and immune-related AEs ascertained from Medicare claims data was estimated using multivariable Cox regression with hazard ratios (HRs) and 95% CIs and with cumulative incidence accounting for competing risk of death. The study included 4489 patients of White race with first primary melanoma (3002 men [66.9%]; median age, 74.9 [range, 66.0-84.9] years). During follow-up (median, 1.4 [range, 0-5.0] years), 1576 patients (35.1%) had an immune-related AE on a Medicare claim. Use of ICIs (reported for 418 patients) was associated with autoimmune-related AEs (HR, 2.5; 95% CI, 1.6-4.0), including primary adrenal insufficiency (HR, 9.9; 95% CI, 4.5-21.5) and ulcerative colitis (HR, 8.6; 95% CI, 2.8-26.3). Immune checkpoint inhibitors also were associated with other immune-related AEs (HR, 2.2; 95% CI, 1.7-2.8), including Cushing syndrome (HR, 11.8; 95% CI, 1.4-97.2), hyperthyroidism (HR, 6.3; 95% CI, 2.0-19.5), hypothyroidism (HR, 3.8; 95% CI, 2.4-6.1), hypopituitarism (HR, 19.8; 95% CI, 5.4-72.9), other pituitary gland disorders (HR, 6.0; 95% CI, 1.2-30.2), diarrhea (HR, 3.5; 95% CI, 2.5-4.9), and sepsis or septicemia (HR, 2.2; 95% CI, 1.4-3.3). Most associations were pronounced within 6 months following the first ICI claim and comparable with or without a baseline history of autoimmune disease. The cumulative incidence at 6 months following the first ICI claim was 13.7% (95% CI, 9.7%-18.3%) for autoimmune-related AEs and 46.8% (95% CI, 40.7%-52.7%) for other immune-related AEs. In this cohort study of older adults with melanoma, ICIs were associated with autoimmune-related AEs and other immune-related AEs. Although some findings were consistent with clinical trials of ICIs, others warrant further investigation. As ICI use continues to expand rapidly, ongoing investigation of the spectrum of immune-related AEs may optimize management of disease in patients.

Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors

54-Year-Old Man With Acute Dyspnea on Exertion

BackgroundICIs (PD-1 inhibitors, PDL-1 inhibitors, CTLA-4 inhibitors) are increasingly used to treat various malignancies. The percentage of cancer patients in the US who may benefit from ICIs has increased from...

2642 Background: The effectiveness of immunotherapy is often hindered by the development of immune-related adverse events (IrAE). Racial minorities were under-represented in the key clinical trials that led to the approval of different immune checkpoint inhibitors (ICI). In this study, we explore the side effect profile of immune checkpoint inhibitors in our patient population that comprises almost entirely of minorities, mostly African Americans (AA) and Hispanics. We hypothesize that due to race-based differences in immune milieu of the body and disease susceptibility, the timing and severity of immunotherapy-related IrAE would be different in AA and Hispanics compared to Caucasians. This can translate into a difference in clinical outcomes as well. There have been some suggestions of a positive association of the development of IrAE with cancer survival, although the data is limited and heterogeneous. The purpose of our study is to study the frequency and severity of IrAEs in racial minority groups, compare them with previous clinical trials population, and add valuable real-world data in this underrepresented group of patients. Methods: A retrospective chart review was performed on adult patients with solid malignancies treated with any ICI between January 1, 2015 and April 30, 2022. Patients were classified according to age (greater/equal to 65y or younger), sex, race (self-identified), primary cancer, and type of immunotherapy received. Outcome data using type and severity of IrAE, time to development of IrAE, and any association with clinical outcomes was collected and analyzed using descriptive statistics as well as univariate analysis. Results: A total of 78 patients were included in the final analysis. The mean age was 68 years; 51% were males; 42.3% were Hispanics, 37% were AA, 19.7% were others, and 1% were Whites. Most common malignancy was lung cancer (65.5%). Most common ICI agent used was Pembrolizumab (n = 52) and 2 patients were treated with combination therapy using Ipilimumab and Nivolumab. 41 (52.5%) patients had IrAE of any grade while 9 (11.5%) patients experienced grade 3 side effects. None of the patients experienced grade 4 side effects. Most common IrAE of any grade was hypothyroidism (n = 14) while most common grade 3 side effect was colitis (n = 6). 31 patients were less than 65y of age. There was no significant difference in IrAE in patients less than 65 years of age vs ≥ 65 years (51.6% vs 53.1%) or grade 3 IrAE (9.6% vs 12.7%). Conclusions: In our study population consisting mostly of AA and Hispanics, the rate of IrAE of any grade as well as grade 3 or 4 IrAE with ICI therapy was comparable to what was seen in clinical trials involving these drugs. This data and its potential effects on survival outcomes need to be analyzed in prospective studies involving a larger number of patients.

Figure 2 The results of NMF and hierarchical clustering on the consensus matrix. (A, B) The NMF results and clusters on the TriNetX cohort; C-D: The NMF results and clusters...

Differentiating Acute Interstitial Nephritis From Immune Checkpoint Inhibitors From Other Causes

6571 Background: Immune checkpoint inhibitors (ICIs) have been one of the most significant developments in Oncology over the last decade. Despite being very effective for certain patient subsets, they have a unique side effect profile different from conventional chemotherapy that can manifest as immune-related adverse events (IRAEs). With increasing ICI use, clinicians will increasingly encounter these adverse events and thus, adequate knowledge on recognition and management of IRAEs is very important. Methods: To assess physician knowledge on IRAEs of ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine (EM) and family medicine (FM) as well as to faculty physicians in IM, and FM at 3 tertiary care hospitals in Indiana. Results: We sent the survey to 413 physicians out of which 155 responded with a response rate of 38%. Out of 155 physicians, 110 were residents and 45 were faculty (27 hospitalists and 17 primary care physicians). Pembrolizumab was identified as a checkpoint inhibitor correctly by 79% of physicians, nivolumab by 64% and ipilimumab by 55%. Twenty-five percent of physicians incorrectly believed infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an IRAE site whereas only 57% and 67% were able to identify cardiovascular and renal systems as an IRAE site, respectively. Fifty-nine percent of physicians believed steroids negatively affect efficacy of ICIs and should be used with caution to treat IRAEs. Sixty-five percent of physicians incorrectly thought endocrinopathies due to IRAEs are usually reversible. Most physicians (79%) believed IRAEs most commonly manifest in the first 6 months of treatment. Forty-five percent of FM residents considered antibiotics as the mainstay of treatment in ICI associated immune mediated colitis; this was significantly different from EM (15%) and IM (8%) residents(p = 0.0004). When comparing between residency programs, on a scale of 0-100, IM residents felt significantly more comfortable identifying IRAEs secondary to ICIs (27.1±24.2) when compared to EM (12.2±12.7) and FM residents (9.4±13.8; p = 0.0009). There was no significant difference among IM (19.8±20.1), EM (11.9±13.6), and FM residents (11.6±18.9; p = 0.11) when comparing how comfortable they were in treating IRAEs. When asked what the best way would be to learn about IRAEs, 36% chose printed material and algorithms, 30% picked online teaching module and 30% chose one time in-person lecture from an Oncologist. Conclusions: Resident and faculty physicians in multiple specialties are not comfortable in the management and treatment of IRAEs due to ICIs. Given that most of these physicians are usually the first point of contact with patients, physician education on identification and treatment of IRAEs is needed. Early detection of these toxicities is critical for their resolution.

Periodontitis is an immune-related adverse event associated with immune checkpoint inhibitors: A multi-center cohort study

Postherpes zoster programmed death-1 inhibitor−associated zosteriform granulomatous reactions

Objectives:The study focuses on evaluating the side effects of immune checkpoint inhibitors (ICIs) in cancer patients. ICIs such as CTLA-4 and PD-1 have emerged as a crucial treatment option in...