Maria Suarez-Almazor's research while affiliated with University of Texas MD Anderson Cancer Center and other places

Simple Summary Our results can be used in clinical settings to facilitate patient–provider discussion. They can also be used to develop educational interventions to increase knowledge and decrease uncertainty. We identified seven key informational needs: (1) possible adverse events; (2) benefits of ICI; (3) ICI mechanism of action in the context of autoimmune disease; (4) management of flare-ups while receiving ICI; (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 adverse events. Abstract 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.

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.

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.

Background Managing immune-related adverse events (irAEs) has become a critical challenge with the increasing implementation of immune-checkpoint inhibitors (ICIs) in cancer treatment. IrAEs may cause treatment interruption or discontinuation, the rate of which is higher with multi-agent ICI regimen needed to overcome resistant tumor microenvironment. Herein, we describe our clinical experience using interleukin-6 receptor antagonists (IL-6RA) to manage irAEs in cancer patients receiving ICIs. Methods We conducted a retrospective, multi-center study to evaluate the safety and efficacy of IL-6RA for irAE management. Eligible patients were identified from the institutional databases (pharmacy records, tumor registries, oncology and specialty clinic records for diagnosis and management of irAEs). The primary objective was assessing changes in irAE symptoms. The secondary objective was assessing overall response rate (ORR) before and after IL-6RA treatment. Results A total of 81 patients received an IL-6RA (tocilizumab or sarilumab); median age was 66 years, 41% were females, 70% received single-agent anti-PD-1 and 23% received nivolumab plus ipilimumab. Cancer types were primarily melanoma (44%), genitourinary cancer (37%), and lung cancer (8.6%). Indications for using IL-6RA were inflammatory arthritis (74%), polymyalgia rheumatica (6%), myositis/myocarditis/myasthenia gravis (5%) encephalitis (5%), and 1% each with pneumonitis, colitis, hepatitis, central nervous system vasculitis, oral mucositis, and flare of pre-existing myasthenia gravis, psoriasis, and Crohn's disease. Notably, 83 % of patients received corticosteroids as first-line therapy, and 29% received disease-modifying antirheumatic drugs, without improvement. After initiation of IL-6RA, improvement of irAEs was observed in 78% after a median of 2.1 months. Of evaluable patients with inflammatory arthritis, the median clinical disease activity index (CDAI) at IL-6RA initiation was 28, indicating high disease activity, and dropped to 6 after treatment, indicating low disease activity. The median CRP level at IL-6RA initiation was 59.5 mg/L and dropped to 1.5 mg/L within 10 weeks of treatment. Seventy-two patients tolerated IL-6RA, and nine stopped treatment due to side effects. Thirty-eight patients were evaluated for tumor response by RECIST 1.1 criteria; the ORR was 58% prior to IL-6RA and 66% after treatment. Of 21 evaluable melanoma patients, the ORR was 62% prior to IL-6RA compared to 71% after treatment (figure 1). Conclusions Our study demonstrated that targeting IL-6R could be an effective approach to mitigate autoimmunity while maintaining and possibly boosting tumor immunity. Clinical trials are currently evaluating the safety and efficacy of tocilizumab in combination with ICIs in patients with melanoma, non-small cell lung cancer, and urothelial carcinoma ( NCT04940299 , NCT03999749 ). Ethics Approval The study was approved by The University of Texas MD Anderson Cancer Center intuition's Ethics Board, approval number PA19-0089 Abstract 816 Figure 1 A patient with sinonasal malignant melanoma involving the ethmoid air cells. (A) Baseline maximum intensity projection (MIP) PET image at 1 month before initiation of ICI (ipilimumab and nivolumab) shows avid FDG uptake of the tumor at the ethmoid air cells (arrow). (B) MIP PET image at 7 months after ICI initiation shows resolution of the FDG uptake at the site of the tumor, consistent with complete response. (C) Concurrent MIP PET and corresponding fused PET-CT images 7 months after initiation of ICI show avid radiotracer uptake at the knee joints, suggestive of arthritis. (D) MIP PET image at 10 months after concomitant therapy with IL6R antagonist and nivolumab shows persistent absence of hypermetabolic radiotracer activity at the paranasal sinuses, consistent with complete response. (E) Concurrent MIP PET and corresponding fused PET-CT images show physiologic radiotracer uptake at the knee joints, consistent with resolving arthritis.

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy. METHODS A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021. RESULTS The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell–related toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell–associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell–associated neurotoxicity syndrome should be managed with corticosteroids and supportive care. Additional information is available at www.asco.org/supportive-care-guidelines .

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitor (ICPi) therapy. METHODS A multidisciplinary panel of medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to update the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 through 2021. RESULTS A total of 175 studies met the eligibility criteria of the systematic review and were pertinent to the development of the recommendations. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS Recommendations for specific organ system–based toxicity diagnosis and management are presented. While management varies according to the organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert ≤ grade 1. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids. Corticosteroids should be tapered over the course of at least 4-6 weeks. Some refractory cases may require other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines .

As the use of cancer immunotherapy expands, a personalized benefit-risk profile of these agents needs to be considered in special populations at higher risk of experiencing adverse events with these agents. Cancer patients with preexisting autoimmune conditions or those who experience rheumatic adverse events with immunotherapy are faced with difficult decisions regarding their treatment. Often, therapeutic gains in survival need to be balanced with a deleterious impact on quality of life. Risk consideration should include types of potential benefits and harms, magnitude of effects, alternative therapeutic options, and, most importantly, patient values and preferences. Future research should aim to quantify risks in these special populations to ensure evidence-based decision-making that considers patient trade-offs between quality of life and survival.

Women with estrogen receptor‐positive breast cancer who receive an aromatase inhibitor (AI) are at risk for fractures. We aim to determine if dual‐energy X‐ray absorptiometry (DXA) scans made at the time of AI initiation are associated with decreased fractures. We retrospectively identified 25,158 women with local or regional breast cancer diagnosed between 2005 and 2013, who received AI therapy between 2007 and 2013, from the Medicare‐linked Surveillance, Epidemiology and End Results Program and Texas Cancer Registry databases. We defined baseline DXA screening using claims made between 1 year prior and 6 months after each patient's first AI claim, to examine determinants of baseline screening using a multivariable GENMOD model. We included a propensity score adjustment in Cox proportional hazard models to assess the association between time‐varying DXA screening and the risk of fractures. Additionally, we compared the use of anti‐resorptive therapies drugs between the two groups. Of the study cohort, 14,738 (58.6%) received DXA screening. The screening rates increased annually from 52.1% in 2007 to 61.7% in 2013. Higher screening rates were observed in patients with younger age, married status, non‐Hispanic white race, localized disease, fewer comorbidities, more than one type of aromatase inhibitor drug claim, no state buy‐in (surrogate for low socioeconomic status), higher education level, and prior osteoporosis diagnosis. Baseline DXA screening was associated with decreased risk of subsequent fractures (hazard ratio = 0.91; 95% confidence interval, 0.86‐0.97, P < 0.001) after multivariable and propensity score adjustment. Bone‐modifying drugs were prescribed to 4,440 (30.1%) patients with screening compared with 1,766 (16.9%) without (P < 0.001). Of the 4,440 patients who received treatment, 95% received bisphosphonates. Our study demonstrated baseline DXA screening was associated with a decreased risk of fractures and a higher likelihood of receiving anti‐resorptive therapies. Improvement of the baseline DXA screening is still needed in practice.

With the increasing use of immune checkpoint inhibitors (ICI) across various cancers, the trends for indication at earlier stages, and the use of combination immunotherapy, the frequency of ICI-induced immune-related adverse events (irAE) is expected to grow substantially. Management of these irAE is challenging as it requires not only consideration of the toxicity but also risk-benefit ratios with respect to the primary cancer. Several rheumatic irAE have been reported with ICI therapy including arthritis, myositis, polymyalgia-like syndromes, sicca/Sjogren-like manifestations, and several other less common systemic autoimmune features commonly associated with connective tissue disease. This handbook provides clinicians with a comprehensive overview of the management of rheumatic irAE that develop from cancer immunotherapy. It focuses on the irAE seen with ICI, the most frequently used agents in treating cancer. It provides an overview of cancer immunology, immunotoxicity, and immunotherapies such as ICI, cytokine-based therapy, and CART. It examines the epidemiology, clinical manifestations, diagnosis, differential diagnosis, and treatment of a variety of rheumatic immune-related adverse events arising from these therapies. Chapters also cover cancer immunotherapy in patients with preexisting rheumatic diseases such as inflammatory arthritis and other connective tissue disorders. The book helps clinicians to distinguish the current types of cancer immunotherapy and general toxicity patterns, recognize and diagnose rheumatic clinical syndromes, understand the pathogenesis of irAE, and consider risk–benefit ratios when managing patients with rheumatic irAE. Rheumatic Diseases and Syndromes Induced by Cancer Immunotherapy is an essential resource for physicians and related professionals, residents, fellows, graduate students and nurses alike in rheumatology, clinical immunology, oncology, and internal medicine.