More than age: Impact of comorbidity and polypharmacy on immune-related adverse events, treatment discontinuation, and toxicity management in older patients receiving immune checkpoint inhibitors.

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

<h3></h3> Immune checkpoint inhibitors have transformed the treatment of various cancers including metastatic melanoma. Immune checkpoints are regulatory mechanisms which modulate the immune system and prevent overwhelming autoimmune attack. This may be exploited by certain tumour types, leading to attenuation of T cell activation and thus expansion and growth of tumour cells. Blockade of pathways including CTLA-4, PD-1 and PDL-1 has emerged as an approach to remove this inhibitory immune checkpoint mechanism and allow host to mount immune responses against tumour cells.^{1 2} Immune related adverse events (irAEs) are important, as high grade toxicities may require corticosteroids and discontinuation of treatment. The incidence of high grade irAEs is greater with CTLA-4 inhibitors (ipilimumab) than PD-1 inhibitors (nivolumab), and risk is increased further in combination (Ipi/Nivo). Ipi/Nivo induced hepatitis is an important irAE occurring in 17.6% patients (any grade) with 8.3% experiencing grade 3/4 hepatitis, based on previous trial data.^3–6 Continued analysis of real-world data is important to better establish the natural history of immunotherapy related hepatitis. Lancashire Teaching Hospitals is the tertiary cancer centre for Lancashire and South Cumbria. Electronic records, biochemistry results and oncology prescribing databases were retrospectively analysed for 68 patients treated with Ipi/Nivo between August 2016 and October 2020. 36 (52.9%) patients experienced hepatotoxicity (any grade) with n= 11 (16.2%) patients developing grade 3 or 4 hepatitis. The median time of onset of hepatotoxicity from the first dose (all grades) was 40 days (range 8–322). Amongst patients who experienced hepatotoxicity, the proportion treated with intravenous, oral or nil corticosteroids was 47.2%, 38.9% and 13.9% respectively. 4 patients required escalation to MMF and 1 patient needed tacrolimus as a third agent. Of patients who developed hepatotoxicity, n=29 had combination treatment discontinued prior to completion of 4 cycles. 15 patients were re-challenged with single agent nivolumab. Of the patients re-challenged, n=9 (60%) did not experience any further hepatotoxicity. This data demonstrated Ipi/nivo induced hepatitis occurring at a higher rate than in reported studies. This highlights the importance in monitoring real world data with novel anti-cancer therapies however, larger collaborative datasets are required. In addition, further comparative effectiveness research regarding treatment with oral vs intravenous corticosteroids will be important. The latter usually requires hospital admission, which has cost, service and patient experience implications. Finally, further analysis of phenotypic and biochemical variables associated with hepatotoxicity may identify important trends to allow better prediction and thus appropriate counselling and informed discussion when planning treatment. <h3>References</h3> Wei S, <i>et al</i>. Fundamental mechanisms of immune checkpoint blockade therapy. <i>Cancer Discov</i> 2018;<b>8</b>(9):1069–1086. Marin-Acevedo JA, <i>et al</i>. Next generation of immune checkpoint therapy in cancer: new developments and challenges. <i>J Haematol Oncol</i> 2018:<b>11</b>:39. Zhou X, et al. Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis. <i>BMC Med</i> 2020;18:87. Larkin J, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. <i>N Eng J Med</i> 2015;373:23–34. Hodi F, et al. Improved survival with ipilimumab in patients with metastatic melanoma. <i>N Eng J Med</i> 2010;363:711–723. Wolchok J, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 2010;11(2):155–64. U.S Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. November 2017. Haanen J, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. <i>Ann Oncol</i> 2017;28(suppl 4):119–142. Cheung V, et al. Immunotherapy-related hepatitis: real-world experience from a tertiary centre. <i>Frontline Gastroenterology</i> 2019;10:364–371. Eun Y, <i>et al</i>. Risk factors for immune-related adverse events associated with anti-PD-1 pembrolizumab. <i>Sci Rep</i> 2019;<b>9</b>:14039. Owen D, <i>et al</i>. Incidence, risk factors, and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer. <i>Clin Lung Cancer</i> 2018;<b>19</b>(6):893–900. Parmanande A, <i>et al</i>. Risk factors for immune related adverse events: a retrospective study. <i>Ann Oncol</i> 2019;<b>30</b>(suppl11). Barata M, <i>et al</i>. Predictors of immunotherapy induced immune-related adverse events. <i>Eur Respir J</i> 2019:<b>54</b>(suppl63). Aimono Y, <i>et al</i>. Evaluation of risk factors for immune-related adverse events associated with treatment with immune checkpoint inhibitors. <i>Gan To Kagaku Ryoho</i> 2021;<b>48</b>(1):57–61. Angum F, <i>et al</i>. The prevalence of autoimmune disorders in women: a narrative review. <i>Cureus</i> 2020;<b>15</b>(5):e8094. Fairweather D, <i>et al</i>. Women and autoimmune diseases. <i>Emerg Infect Dis</i> 2004;<b>10</b>(11):2005–2011. Ozdemir B, <i>et al</i>. Immune-related adverse events of immune checkpoint inhibitors and the impact of sex- what we know and what we need to learn. <i>Ann Oncol</i> 2018;<b>29</b>(4):1067.

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

Atypical Antiglomerular Basement Membrane Nephritis Following Immune Checkpoint Inhibitor

Management of older and frail patients with multiple myeloma in the Portuguese routine clinical practice: Deliberations and recommendations from an expert panel of hematologists

Introduction: Geriatric assessment (GA) is recommended for evaluating an older cancer patient’s fitness for treatment; however, it is underutilized in the community. We sought to define the gaps that exist in community oncology practices in the assessment and management of older MBC patients through implementation and training on the use of GA for the care of older MBC patients. Methods: The first phase evaluated community oncology providers using questionnaires regarding their assessment and management of older MBC patients. The second phase included training through implementation of a patient self-administered GA among patients ≥65-years-old with MBC. The providers were blinded to the results of the GA and provided their assessment. Comparison of the 2 evaluations was conducted. The GA was ultimately shared with the providers, who were questioned about the effect of the results on care recommendations. Results: 43 providers from 10 practices were enrolled. Phase I revealed the majority (77%) of providers recognized the utility of GA, yet only 42% routinely conducted a GA pretreatment. Most providers (77%) reported evaluating various GA domains through patient interview rather than validated assessments. Validated scales were used in low rates to evaluate cognition (23%), psychosocial status (12%), and toxicity risk (9%). The limited use of validated assessment tools was not influenced by the provider’s demographics or their views of GA utility. Eighty patients took part in the training phase of the study to date, with average age 74 (range, 65–90) and 84% Caucasian. The majority of patients had subtype ER/PR+, HER2- (75%) and 46% were on first-line therapy. 277 recommended interventions were identified: 174 immediate interventions and 103 suggested interventions. Following review of these results, providers reported being surprised in 40% of the cases, mainly with lower than expected cognitive or social support scores. The providers reported plans for change in management in 44% of the patients as a result of the GA findings. Conclusion: Despite acknowledgement of the value associated with pretreatment GA, it is rarely used in the community. Furthermore, interview rather than validated assessment tools are used to identify age-related concerns. In our preliminary results, the GA identified a large number of deficient areas that had not been identified through the provider’s assessment, and resulted in management change. Additional updated results will be presented at the conference.

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.

This review article examines the role of orthogeriatric management for frail older patients with a fragility fracture. The history of orthogeriatrics and its application in clinical practice around the world is reported, and an evidence-based evaluation for the effect of orthogeriatric management on patient morbidity and mortality is also provided. It has been more than 50 years since the role of the geriatrician in the management of patients with a hip fracture was first described. The evidence that supports an orthogeriatric model of care has grown exponentially over the last decade. This evidence base is primarily related to hip fractures and demonstrates reduced morbidity and mortality rates amongst patients managed with a recognised model of orthogeriatric care. The societal and economic burden of hip fracture has led to health economic evaluations within this field, many of which have concluded that orthogeriatric management results in cost-effective clinical practice. Based on existing clinical and economic research, national clinical practice guidelines have been developed in several countries which recommend orthogeriatric participation in the management of older patients with a hip fracture. Compliance with such guidance has already demonstrated improved patient outcomes. Although the pathogenesis and prognosis of other types of fragility fracture may be as poor, there is a dearth of clinical research that evaluates the effect of orthogeriatric management on such injuries. Looking to the future, orthogeriatric management is likely to become more widespread, and the robust collection and reporting of patient outcomes from national registries will provide a greater understanding of the impact of orthogeriatric models in the care of all frail older patients with any type of fragility fracture.

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized cancer therapy over the last decade. Despite the efficacy of ICIs, immune-related adverse events (irAEs) occur in over a third of treated patients and...

Background: Immune checkpoint inhibitors (ICI) have tremendously improved outcomes for various cancers but can be associated with immune-related adverse effects (IrAE), which can affect multiple organ systems. For patients with pre-existing autoimmune diseases (AD), there is an added risk of exacerbating autoimmunity, either through a flare of prior IrAEs or the development of de novo IrAEs during ICI therapy. Clinical trials leading up to FDA approval of ICIs excluded patients with pre-existing AD, resulting in a lack of data on the specific risks faced by this patient population. Our study aims to assess whether patients with pre-existing AD are more likely to develop IrAEs when treated with ICIs, and if so, whether these IrAEs are more severe. Methodology: We conducted a retrospective chart review of all patients diagnosed with AD and received ICIs for treatment of a solid tumor malignancy within the Geisinger Health System from January 1, 2017, to December 31, 2023. We analyzed the occurrence, subtype, and severity (grade) of IrAEs based on the Common Terminology Criteria for Adverse Events (CTCAE). Additionally, we assessed steroid use, treatment discontinuation, and hospitalization rates. Results: A total of 250 patient charts were identified using the cancer registry, 105 of them were excluded due to the absence of a pre-existing AD. Of the 145 patients with a pre-existing AD, 59 (40.7%) developed an IrAE, and 21 (14.5%) developed a severe (grade 3/4) IrAE. Additionally, 44 (30.3%) patients required steroids for the treatment of IrAE, and 12 (8.3%) were hospitalized due to an IrAE. The most prevalent IrAEs were colitis, rash, hypothyroidism, transaminitis, and pneumonitis, which occurred in 52 (35%) cases; of these, 13 (8.9%) were severe (grade ¾). Discussion: When comparing our results to those of previous studies, we found that the rates and severity of IrAEs were higher in patients with pre-existing AD compared to historical data on patients without AD. A meta-analysis by de Velasco et al. of 21 studies reported an IrAE incidence of 28% for all grades and 5% for grades 3 and 4. Similarly, Silverstein et al. analyzed 3,137 patients treated with ICIs and found that 3.8% were hospitalized due to IrAEs. These significant differences underscore the need for multidisciplinary collaboration and heightened monitoring for IrAEs in patients with AD. Citation Format: Aseel Saadeh, Pragosh Saini, Favour Nelson, Sumera Khan, Christian Adonizio, Ahmad Hanif. Immune-related adverse effects in patients with autoimmune disorders treated with immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5814.

PORTRET, a more inclusive portrait of the older population with breast cancer

<h3>Background</h3> Immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy can involve multiple organ systems, of which cutaneous irAEs (c-irAEs) are the most common.^1–5 Understanding co-occurrence patterns and...

The incidence of melanoma in older patients is on the rise. Prior studies have shown disparities in surgical management and poor survival of older patients with melanoma. This is a retrospective study of adult patients diagnosed with cutaneous invasive and in situ melanoma between 2000 and 2011 in the National Cancer Data Base. Characteristics and management of older patients (≥60 years) were compared with younger patients (20-59 years) using χ(2) testing. Of 476,623 total cases, 54% (n = 258,153) were diagnosed among older patients. The reported cases in the older patients increased by 1.74-fold between 2000 and 2011. The majority were white (96%), men (65%), with early-stage disease (76% stage 0-II), and superficial spreading melanoma histology (39%). Older patients, compared with younger patients, were more likely to be men (65% versus 49%, p < 0.0001), and have in situ melanoma (28% versus 21%, p < 0.0001); less likely to have nodal metastases (7% versus 9%, p < 0.0001), receive care in academic centers (30% versus 35%, p < 0.0001), undergo wide excision or major amputation for stage I-III disease (68% versus 72%, p < 0.0001) and systemic therapy for stage III (18% versus 45%, p < 0.0001) and IV disease (30% versus 50%, p < 0.0001). Older patients with melanoma are less likely to receive care in academic centers, undergo wide excision for stage I-III disease and receive systemic therapy for stage III-IV disease. Particularly, the utilization of systemic therapy is markedly low. This disparity is particularly important with the availability of less intense more effective therapies.

Characteristics and Outcomes of Older Patients With Classical Hodgkin Lymphoma: An Australasian Lymphoma Alliance, and Lymphoma and Related Diseases Registry Study.

BackgroundImmune checkpoint inhibitors (ICIs) are limited by the high incidence of immune-related adverse events (irAEs) occurring in up to 40% of solid tumor patients on anti-PD-1 monotherapy 1 2 and...