A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease.

BACKGROUND: Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs. METHODS: We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths. RESULTS: A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease. CONCLUSIONS: Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.

Factors Associated With Adherence of Cervical Cancer Screening in Women With Systemic Lupus Erythematosus.

OBJECTIVE: The objective is to determine cervical cancer screening rates and factors associated with decreased cervical cancer screening in women with systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional study that enrolled consecutive women (age 21-64 years) with SLE. We collected demographics, clinical characteristics, constructs of the Health Beliefs Model (HBM) (ie, susceptibility, severity, barriers, benefits, cues to action, and self-efficacy), and self-reported cervical cancer screening (confirmed with the electronic medical record). The primary outcome was adherence to cervical cancer screening according to current guidelines. Multivariable logistic regression models were used to examine the association between SLE disease activity and cervical cancer screening and explore mediation effects from HBM constructs. RESULTS: We enrolled 130 women with SLE. The median age was 42 years (interquartile range 32-52 years). The cervical cancer screening adherence rate was 61.5%. Women with high SLE disease activity were less likely to have cervical cancer screening versus those with low disease activity (odds ratio 0.59, 95% confidence interval [CI] 0.39-0.89; P = 0.01), which remained statistically significant after adjusting for baseline demographics and drug therapy in a multivariable model (odds ratio 0.25, 95% CI 0.08-0.79; P = 0.02). Regarding the HBM constructs, increased perceived barriers to cervical cancer screening (r = -0.30, P < 0.01) and decreased self-efficacy (r = -0.21, P = 0.02) correlated with decreased cervical cancer screening. CONCLUSION: Patients with SLE with high disease activity undergo cervical cancer screening less frequently than those with low disease activity. Perceived barriers to cervical cancer screening are moderately correlated with decreased screening. These data highlight the need to develop strategies to increase cervical cancer screening in this high-risk patient population.

Mimickers of Immune Checkpoint Inhibitor-induced Inflammatory Arthritis.

The differential diagnosis of inflammatory arthritis as an immune-related adverse event can be challenging as patients with cancer can present with musculoskeletal symptoms that can mimic arthritis because of localized or generalized joint pain. In addition, immune checkpoint inhibitors can exacerbate joint conditions such as crystal-induced arthritis or osteoarthritis, or induce systemic disease that can affect the joints such as sarcoidosis. This distinction is important as the treatment of these conditions can be different from that of immune-related inflammatory arthritis.

Immune Checkpoint Inhibitor-induced Myositis.

Myositis induced by immune checkpoint inhibitors (ICIs) is an infrequent, potentially fatal, immune-related adverse event. It has higher incidence in patients who receive combination ICI therapy compared to monotherapy. Patients can present with clinical manifestation symptoms of myositis alone or in combination with myocarditis and/or myasthenia gravis, which significantly worsens the course and prognosis. Diagnosis can generally be made on the basis of clinical presentation, elevation of muscle enzymes, and electromyographic changes, but some patients may require a muscle biopsy. The first line of therapy is high-dose corticosteroids, followed by immunosuppression, plasmapheresis, or intravenous immunoglobulin in patients with severe disease.

Rheumatic adverse events of immune checkpoint inhibitors in cancer immunotherapy.

INTRODUCTION: The advent of immune checkpoint inhibitors (ICIs) in cancer treatment has marked a transformative era, albeit tempered by immune-related adverse events (irAEs), including those impacting the musculoskeletal system. The lack of precise epidemiologic data on rheumatic irAEs is attributed to factors such as potential underrecognition, underreporting in clinical trials, and the tendency to overlook manifestations without immediate life-threatening implications, further complicating the determination of accurate incidence rates, while the complete understanding of the mechanisms driving rheumatic irAEs remains elusive. AREAS COVERED: This literature review comprehensively examines rheumatic irAEs in cancer patients undergoing ICI therapy, encompassing epidemiology, risk factors, mechanisms, clinical manifestations, and current management guidance for prevalent conditions such as inflammatory arthritis, polymyalgia rheumatica, and myositis. Less frequent rheumatic and musculoskeletal irAEs are also explored, alongside insights into ongoing clinical trials testing therapeutic and preventive strategies for irAEs. A thorough literature search on Medline and the National Cancer Institute Clinical Trials Database was conducted up to October 2023 to compile relevant information. EXPERT OPINION: In light of the evolving landscape of cancer immunotherapy, there is a compelling need for prospective longitudinal studies to enhance understanding and inform clinical management strategies for rheumatic irAEs.

Utilization of Biologic Disease-Modifying Antirheumatic Therapy in Patients With Rheumatoid Arthritis and Recently Diagnosed Breast Cancer.

OBJECTIVE: Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis. METHODS: We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after BC. We conducted multivariable logistic regression to evaluate the association of utilization with patient characteristics. RESULTS: A total 1,412 patients were identified in CDM and 1,439 patients in SEER/TCR-Medicare. During the three months before BC diagnosis, 28.2% (CDM) and 26.9% (SEER/TCR-Medicare) patients had received bDMARDs. Within the first three years after diagnosis, 24.1% (CDM) and 26.4% (SEER/TCR-Medicare) were receiving bDMARDs. About 70% of the patients in the two cohorts received glucocorticoids with no significant time trend increases. The largest predictor of bDMARD utilization was prior use before BC (CDM: odds ratio [OR] 27.15, 95% confidence interval [CI] 19.29-38.19; SEER/TCR: OR 18.98, 95% CI 13.72-26.26). Regional and distant BC compared to in situ or localized were also associated with lower bDMARDs utilization in SEER/TCR-Medicare (OR 0.54, 95% CI 0.36-0.82; OR 0.31, 95% CI 0.13-0.77, respectively). CONCLUSION: The utilization of tumor necrosis factor inhibitors and other bDMARDs in patients with RA and recent BC has not increased since 2008. Glucocorticoids utilization remained high. The largest predictor of bDMARD utilization was prior use before BC.

Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases.

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35-3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95-5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

Case Report: Immune checkpoint inhibitor-induced multiorgan vasculitis successfully treated with rituximab.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. ICIs have a unique side effect profile, generally caused by inflammatory tissue damage, with clinical features similar to autoimmune conditions. Acute kidney injury from ICIs has been well studied; incidence ranges from 1% to 5%, with higher incidence when combination ICI therapies are used. Although the overall reported incidence of ICI-associated glomerulonephritis is less than 1%, vasculitis is the most commonly reported ICI-related glomerulonephritis. Other biopsy findings include thrombotic microangiopathy, focal segmental glomerulosclerosis, minimal change disease, and IgA nephropathy with secondary amyloidosis. We report a case in which a woman previously treated with the PD-L1 inhibitor durvalumab for locally advanced non-small cell lung cancer with pre-existing antineutrophil cytoplasmic (anti-PR3) antibody who later developed multi-organ vasculitis after ICI exposure, which was successfully treated with rituximab, with continued cancer remission for 3 years.

Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors.

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee's opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.

Physician Views on the Provision of Information on Immune Checkpoint Inhibitor Therapy to Patients with Cancer and Pre-Existing Autoimmune Disease: A Qualitative Study.

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide information to patients and delivery options; (2) factors to make decisions about whether or not to start ICIs in patients who have cancer and pre-existing autoimmune conditions; (3) learning points for patients to understand; (4) preferences for the delivery of ICI information; and (5) barriers to the implementation of ICI information in clinics. Regarding points to discuss with patients, physicians agreed that the benefits of ICIs, the probability of irAEs, and risks of underlying autoimmune condition flares with the use of ICIs were most important. Non-oncologists were additionally concerned about how ICIs affect the autoimmune disease (e.g., impact on disease activity, need for changes in medications for the autoimmune disease, and monitoring of autoimmune conditions).

Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events.

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs. METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment. RESULTS: We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04). CONCLUSION: Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).

COVID-19 Outcomes in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review.

Introduction: Immune checkpoint inhibitors (ICIs) can cause inflammatory and immune-related adverse events (irAEs) that might worsen the course of COVID-19. We conducted a systematic review (PROSPERO ID: CRD42022307545) to evaluate the clinical course and complications of COVID-19 in patients with cancer receiving ICI. Methods: We searched Medline and Embase through January 5, 2022. We included studies evaluating patients with cancer who received ICI and developed COVID-19. Outcomes included mortality, severe COVID-19, intensive care unit (ICU) and hospital admissions, irAEs, and serious adverse events. We pooled data with random effects meta-analysis. Results: Twenty-five studies met study eligibility (n = 36,532 patients: 15,497 had COVID-19 and 3220 received ICI). Most studies (71.4%) had a high risk of comparability bias. There were no significant differences in mortality (relative risk [RR] 1.29; 95% CI 0.62-2.69), ICU admission (RR 1.20; 95% CI 0.71-2.00), and hospital admission (RR 0.91; 95% CI 0.79-1.06) when comparing patients treated with ICI with patients without cancer treatment. When pooling adjusted odds ratios (ORs), no statistically significant differences were observed in mortality (OR 0.95; 95% CI 0.57-1.60), severe COVID-19 (OR 1.05; 95% CI 0.45-2.46), or hospital admission (OR 2.02; 95% CI 0.96-4.27), when comparing patients treated with ICIs versus patients with cancer without ICI therapy. No significant differences were observed when comparing clinical outcomes in patients receiving ICIs versus patients receiving any of the other anticancer therapies. Conclusion: Although current evidence is limited, COVID-19 clinical outcomes of patients with cancer receiving ICI therapy appear to be similar to those not receiving oncologic treatment or other cancer therapies.

Smoking cessation patterns, usefulness of quitting methods, and tobacco cessation motivators and barriers to quit in patients with rheumatoid arthritis.

OBJECTIVE: Tobacco use is highly discouraged in patients with rheumatoid arthritis (RA) due to related short and long-term health implications. We aimed to evaluate smoking cessation patterns in patients with RA. In addition, we ascertained perceptions on the usefulness of quitting methods, and perceived motivators and barriers to quit. METHODS: We surveyed adults with RA enrolled in the FORWARD Databank who self-identified as former or current tobacco users. RESULTS: Three hundred forty-eight participants completed the survey and responded to the question "do you currently smoke" (former use = 319; current use = 29). Nicotine replacement therapy (NRT) was perceived as extremely/somewhat useful by 31%, followed by individual 27% and group counseling 21%. Experiencing a major health event was the most common motivator to quit. Current users on average smoked 17 cigarettes per day. Six of the 29 current users had used electronic cigarettes in the past 30 days. The most frequent methods used to quit were "cold turkey quitting," NRT, and prescription medicines. Only 8 of the 23 current users had plans to quit or expressed being ready to make changes to quit. Reasons most frequently listed to not quit were using smoking to manage negative emotions, as a pleasurable habit, to manage other addictions, and to provide a sense of control (e.g., to cope with RA). CONCLUSIONS: Current users expressed several negative emotions including coping with the disease and "being a pleasurable habit" when trying to quit. Future cessation programs should address these barriers to support patients with RA. Key Points • First study characterizing the smoking behavior of patients with RA in the USA. Current users were younger, had a shorter disease duration, and worse disease outcomes compared to former smokers. • Former and current users reported similar motivators to quit, with experiencing a major health event being most common. Only about a third of participants who quit or who were still smoking received advice from a health professional. • The most common reasons for not quitting were that smoking help to manage negative emotions and was a pleasurable habit. Future studies should focus on cessation programs that support participants with RA by addressing the unique perceptions about smoking in this population.

Society for Immunotherapy of Cancer (SITC) consensus definitions for immune checkpoint inhibitor-associated immune-related adverse events (irAEs) terminology.

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.

A systematic review and meta-analysis of e-cigarette use among cancer survivors.

PURPOSE: We conducted a systematic review and meta-analysis to determine the use of e-cigarettes among cancer survivors, factors associated with their use, and prevalence of e-cigarette use as a quit attempt. METHODS: We searched five electronic databases until June 2022. Two authors independently selected studies, appraised their quality, and collected data. RESULTS: Twenty-three publications from eight data sources (national surveys) met our eligibility criteria. The pooled rate of lifetime e-cigarette use among cancer survivors was 15% (95% CI 6-27%); current use was 3% (95% CI 0-8%). Among survivors who currently used traditional cigarettes, 63% (95% CI 57-69%) also used e-cigarettes. The reported rates of weighted lifetime e-cigarette use differed between age groups (18-44 years, up to 46.7%; 45-64, up to 27.2%; ≥65, up to 24.8%). Nine publications reported factors associated with lifetime e-cigarette use (i.e., active use of traditional cigarettes; heavy drinking; poor mental health; younger age; being male, non-Hispanic White, or single; having less than high school education or income ≤$25,000 USD; and living in the South regions of the US or urban areas). E-cigarettes were used as a quit resource by 75% of survivors reporting dual use of electronic and traditional cigarettes (95% CI 63%, 85%). CONCLUSION: More than two-thirds of survivors currently using traditional cigarettes also use e-cigarettes. Higher use rates of e-cigarettes were reported among young cancer survivors compared to older survivors. Future studies are needed to assess the impact of e-cigarettes on long-term health and improve screening of smoking behaviors. IMPLICATIONS FOR CANCER SURVIVORS: Our study provides an overview of the prevalence of e-cigarette use and sociodemographic risk factors associated with e-cigarette use among cancer survivors. The findings can assist providers in supporting attempts to quit among cancer survivors.

COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune response that could induce or aggravate irAE. METHODS: The objective of this systematic review is to appraise the efficacy and safety of COVID-19 vaccination in patients with cancer treated with ICI. The literature search was performed in PubMed and Embase in English from December 2019 to February 2022. The review included clinical trials, observational cohort studies, case series, and case reports reporting on the clinical efficacy and safety of COVID-19 vaccines on patients with cancer treated with ICI. Outcomes of interest included seroconversion, SARS-CoV-2 infection rate, severe COVID-19, COVID-19 mortality rate. Incidence of ICI irAEs was also ascertained as well as vaccine adverse events. A meta-analysis was conducted to estimate the pooled effect sizes of the outcomes when possible, using random effects models. RESULTS: Overall, 19 studies were included for the analysis (n=10 865 with 2477 receiving ICI). We analyzed 15 cohort studies, 1 cross-sectional study, and 3 case reports. There were no statistically significant differences in seroconversion rates after the second dose of the vaccine when comparing patients with cancer receiving ICI with patients without cancer (risk ratio, RR 0.97, 95% CI 0.92 to 1.03) or with patients with cancer without active treatment (RR 1.00, 95% CI 0.96 to 1.04). There was a higher probability of seroconversion in patients with cancer treated with ICI compared with patients with cancer treated with chemotherapy (RR 1.09, 95% CI 1.00 to 1.18). In a single study in patients receiving ICI, no differences were observed in risk of irAE between those receiving inactivated vaccine and those unvaccinated (pneumonitis RR 0.88, 95% CI 0.33 to 2.3; rash RR 1.03, 95% CI 0.66 to 1.62; arthralgia RR 0.94, 95% CI 0.51 to 1.75). There were no studies for other types of vaccines comparing vaccinated vs not vaccinated in patients treated with ICI. The most common vaccine-related adverse events were local pain or fatigue. Overall, the quality of evidence was rated as very low. CONCLUSION: COVID-19 vaccination appears to be effective and safe in patients with cancer receiving ICI.

Systemic Lupus Erythematosus and Mortality in Elderly Patients With Early Breast Cancer.

OBJECTIVE: Patients with cancer and systemic lupus erythematosus (SLE) may have worse outcomes than those without SLE, given their comorbidities. We examined survival in elderly women with breast cancer (BC) and SLE and hypothesized that survival would be decreased compared with women with BC but without SLE. METHODS: We identified patients with BC and SLE and patients with BC without SLE in the Texas Cancer Registry and Surveillance, Epidemiology, and End Results, linked to Medicare claims. Overall survival (OS) was estimated after matching (age and cancer stage) and in multivariable Cox proportional hazards models adjusting for other cancer characteristics, treatment, and comorbidities. Two additional cohorts of women without cancer with and without SLE were also studied. RESULTS: We identified 494 BC SLE cases and 145,517 BC non-SLE cases, of whom we matched 9,708. Women with SLE were less likely to receive radiation, breast conserving surgery, or endocrine therapy. The 8-year OS estimate for women with early BC (stages 0-II) with and without SLE was 52% (95% confidence interval [95% CI] 45%-59%) and 74% (95% CI 73%-75%), respectively. In the Cox multivariable model, BC and SLE had increased risk of death (hazard ratio [HR] 1.65, 95% CI 1.38-1.98). Women with BC and SLE also had increased risk of death compared with women with SLE but without cancer (HR 1.42, 95% CI 1.05-1.92) after adjusting for SLE severity. Women with SLE and BC received less glucocorticoids, antimalarials, and immunosuppressants after cancer diagnosis than those without cancer. CONCLUSION: Systemic lupus is a risk factor for increased mortality in women with early BC.

Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group.

INTRODUCTION: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains. METHODS: As the initial step of the core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter. RESULTS: We identified 69 publications, over a third of which utilized non-specific diagnoses of "arthritis," "arthralgia," and/or "PMR". Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 subsequent response, as well as 32 tumor response. CONCLUSION: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. There were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use.

A systematic review with meta-analysis of the effects of smoking cessation strategies in patients with rheumatoid arthritis.

OBJECTIVE: Smoking rates among patients with rheumatoid arthritis (RA) exceed those in the general population. This study identified smoking cessation strategies used in patients with RA and synthesized data on their effects. METHODS: We conducted a systematic review of studies that reported effects of interventions for smoking cessation in patients with RA. We searched 5 electronic databases until March 2022. Screening, quality appraisal, and data collection were done independently by 2 reviewers. RESULTS: We included 18 studies reporting interventions for patients or providers: 14 evaluated strategies for patients (5 education on cardiovascular risk factors including smoking, 3 educational interventions on smoking cessation alone, 3 education with nicotine replacement and counseling, and 1 study each: education with nicotine replacement, counseling sessions alone, and a social marketing campaign). Smoking cessation rates ranged from 4% (95% CI: 2%-6%, 24 to 48 weeks) for cardiovascular risk education to 43% (95% CI: 21%-67%, 104 weeks) for counseling sessions alone. The pooled cessation rate for all interventions was 22% (95% CI: 8%-41%, 4 weeks to 104 weeks; 9 studies). Four interventions trained providers to ascertain smoking status and provide referrals for smoking cessation. The pooled rates of referrals to quit services increased from 5% in pre-implementation populations to 70% in post-implementation populations. CONCLUSION: Studies varied in patient characteristics, the interventions used, and their implementation structure. Only 3 studies were controlled clinical trials. Additional controlled studies are needed to determine best practices for smoking cessation for patients with RA.