Interruption Of Immunotherapy Research Articles

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

Immunotherapy-Associated Immune Thrombocytopenia: Treatment Paradigms

Introduction: Immune cytopenias are a rare but potentially serious complication of immunotherapy (IO) used in the treatment of cancer. Immunotherapy-associated Immune Thrombocytopenia (IO-ITP) is a diagnosis of exclusion and often under recognized in the setting of cancer-directed multidrug regimens. In general it is managed with interruption of IO and disease-specific therapies based on management of the corresponding primary hematologic disorder. Our goal was to identify and characterize IO-ITP and to compare treatment approaches with primary immune thrombocytopenia (p-ITP). Methods: Data was obtained from TriNetX, a de-identified national health research network with data sourced from 76 health care organizations (HCOs) with over 107 million patients located in the United States. We identified all adults (≥18 years) with diagnosis of ITP (ICD-10: D69.3) between 2015-2023. We categorized patients into two cohorts: IO-ITP, those with a diagnosis of ITP after IO use (pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab) and a diagnosis of neoplasm (ICD-10: C00-D49); and p-ITP: those with ITP without neoplasm nor IO use. For both cohorts, we collected demographic, laboratory and treatment characteristics. To compare treatment approaches, we subcategorized cohorts by platelet count to identify patients who would qualify for ITP-directed therapy, using a platelet count ≤75x10 3/µL in IO-ITP and ≤50x10 3/µL in p-ITP. Platelet count cutoffs were defined based on current guidelines recommendations. We investigated the use of first-line and rescue therapies: glucocorticoids and IVIG; second-line therapies: thrombopoietin agonists (TPO-RAs: romiplostim and eltrombopag) and rituximab; third-line therapies: cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, bortezomib, avatrombopag and fostamatinib; and splenectomy, based on guidelines for management of p-ITP. For continuous data, we performed independent t-tests and for categorical data, chi-square tests. All tests were two-tailed with alpha level of .05. Results: In total, we identified 241 individuals with IO-ITP and 14,717 with p-ITP. Individuals with IO-ITP had a mean age of 64 years (21-86) and were predominantly male (57.3%), whereas those with p-ITP, were younger, (mean age 48 years,18-89) and predominantly female (63.2%) (Table). Both groups were mostly white and had similar mean platelet counts. Cancer of the respiratory system (40.7%) followed by skin malignancies (26.1%) were the most common subtypes in those with IO-ITP. Pembrolizumab was the IO most frequently used (52.7%). Within first-line and rescue therapies, a higher proportion of patients with IO-ITP required steroids as compared to those with p-ITP (81.4% vs 58.6%, p value &amp;lt;0.001). There was no significant difference between the groups in the utilization of IVIG. With respect to second-line therapies, in IO-ITP, a greater proportion received TPO-RAs (27.9%) compared to rituximab (6%). More patients with p-ITP received rituximab as compared to IO-ITP (14.9% vs 6%, p value &amp;lt; 0.001). Among TPO-RAs, romiplostim was more commonly used in IO-ITP (19.7% vs 10.9%), whereas eltrombopag was preferred in p-ITP (15.5% vs 10.6%). Similar to p-ITP, the use of third line therapies was infrequent in IO-ITP. No patients with IO-ITP underwent splenectomy, which was also rarely used in p-ITP. Conclusions: Our study describes treatment patterns in IO-ITP, an uncommon but challenging disease. We found that individuals with IO-ITP are generally younger and predominantly male as compared to p-ITP, highlighting different patient profiles. We further demonstrated some distinctions in the management of these two conditions, possibly suggesting variable response to therapy. Prospective studies are needed to better understand the determinants of such therapeutic choices and outcomes.

Ultra-Hypofractionated Re-Irradiation with Anti-PD-1 Immunotherapy for Locoregionally Recurrent (after Radical Chemo-Radiotherapy) Non-Small Cell Lung Cancer.

Large fractions of radiotherapy of 8 Gy (ultra-hypofractionated RT, ultra-hypoRT) promote anti-tumor immune responses that have been clinically substantiated in combination trials with immune checkpoint inhibitors (ICIs). In the current study, we postulated that ultra-hypoRT in combination with ICIs may enhance tumor clearance in NSCLC patients with locoregional relapse after radical chemo-RT. Between 2019 and 2021, eleven patients received re-irradiation with one or two fractions of 8 Gy concurrently with anti-PD1 immunotherapy (nivolumab or pembrolizumab). RT-related toxicities were negligible, while immune-related adverse events enforced immunotherapy interruption in 36% of patients. The overall response rate was 81.8%. Tumor reduction between 80 and 100% was noted in 63.5% of patients. Within a median follow-up of 22 months, the locoregional relapse-free rate was 54.5%, while the projected 2-year disease-specific overall survival was 62%. The results were independent of PD-L1 status. The current report provides encouraging evidence that a relatively low biological dose of RT delivered with 8 Gy fractions is feasible and can be safely combined with anti-PD-1 immunotherapy. Despite the low number of patients, the significant tumor regression achieved and the long-lasting locoregional control and overall progression-free intervals provide a basis to pursue immuno-RT trials with U-hypoRT schemes in this group of NSCLC patients of poor prognosis.

Comorbidities and Their Impact on Treatment Tolerance and Outcome in Elderly NSCLC Patients Treated with Concurrent Chemoradiation Using Proton or Photon Followed by Immunotherapy

To investigate comorbidities and their impact on treatment tolerance and survival for elderly NSCLC patients treated with concurrent chemoradiation using proton beam therapy (PBT) or intensity modulated radiation therapy (IMRT) followed by immunotherapy (IO). This is a retrospective study in senior patients (≥ 65 years) with inoperable locally advanced- NSCLC (LA-NSCLC) who received concurrent chemoradiation (CRT) therapy followed by adjuvant IO. Comorbidities are listed in table 1 and scored according to hazard ratios (HRs) of death. Treatment tolerance and comorbidities were compared between modalities using Fisher's exact test. Association between comorbidities and treatment tolerance was analyzed using logistic regression; association between comorbidities and survival was analyzed by Cox proportional hazards regression. Total 218 patients were included with median age of 72 (range 65-86) years. Fifty-three (24.3%) were PBT and 165 (75.7%) were IMRT. Majority patients were white ethnics, had stage III adenocarcinoma disease and good performance score, and received RT dose 60-66 Gy. The median follow-up time for the whole group was 23 months. A 97% of patients had ≥1, and 62% had ≥4 comorbidities. The combined comorbidity scores ranged from 0 to 25. No significant difference in comorbidities between modalities except IMRT had more patients with COPD (36% vs. 51%, p = 0.047). Rates of hospitalization and ER visit during CRT+IO were 28% and 5%, respectively. Rates of IO discontinuation and interruption were 55% and 8%, respectively. Patients received >6 months IO had significantly lower risk of death (HR: 0.25, p<0.001). No significant difference in treatment tolerance between modalities. In multivariable analysis, atrial fibrillation, pulmonary disease, and depression were the comorbidities associated with hospitalization during CRT+IO (p<0.05); dementia was the comorbidity associated with IO interruption (p = 0.042); heart failure, COPD, asthma, osteoporosis and HIV were the comorbidities associated with poor OS (p<0.05). Combined comorbidity score was associated with OS with HR of 1.13 (p<0.001) with adjustment of race, GTV and induction chemotherapy. Comorbidities were associated with hospitalization and IO interruption during the whole course of CRT and IO therapy, with increased IO discontinuation which negatively impacted survival. Evaluating and scoring comorbidities at diagnosis could be a useful method to predict risk of death before treatment start.

Pembrolizumab-induced erosive lichenoid reaction in a patient with metastatic lung adenocarcinoma: A case report

Introduction: Immune-related adverse events induced by immune checkpoint inhibitors are quite common. Cutaneous lichenoid immune-related adverse events are among the most frequent. However, oral lichenoid adverse reactions are extremely rare. We herein describe a patient who was treated with pembrolizumab for metastatic lung cancer and developed an erosive oral lichenoid reaction induced by immunotherapy. Case presentation: An 87-year-old man treated with pembrolizumab for metastatic lung adenocarcinoma (stage IVa based on AJCC 2018) developed multifocal erosions of the oral mucosa mainly located on the buccal mucosa, palate, and inner portion of the lips with multiple small, irregular, hyperkeratotic areas. Histopathological examination showed epithelial necrosis and a dense band-like layer of an inflammatory infiltrate of lymphocytes and histiocytes within the upper dermis. Direct immunofluorescence was negative for both IgG and C3. A diagnosis of erosive oral lichenoid reaction of the mucosa induced by immunotherapy was established. Given the severity of the condition, pembrolizumab treatment was withheld and concomitant topical and systemic steroids were started. After 1 month, the drug-related toxicity was ameliorated and immunotherapy was re-introduced. Discussion: Only one other case of pembrolizumab-induced erosive lichen planus of the oral mucosa has been described to date. Previously reported drug-induced lichenoid rashes were mainly localized on the skin. Clinically, the main differential diagnoses of lichenoid erosive lesions are bullous immune-related disorders and should be excluded. In our patient, histological examination combined with negative results of both direct immunofluorescence and enzyme-linked immunosorbent assays confirmed the diagnosis of erosive lichenoid drug reaction. Conclusion: Clinicians should be aware of lichenoid involvement of the oral mucosa because related pain and food intake difficulties may seriously compromise treatment compliance. Prompt treatment of oral drug-related reactions may prevent interruption of immunotherapy and improve patients’ quality of life.

1139P A CT-based radiomic readout on the differential diagnosis of pneumonitis in stage IV non-small cell lung cancer patients treated with immune checkpoint inhibitors

About 4-10% patients who receive immunotherapy are subjected to Immunotherapy-Induced Pneumonitis (IIP) which is a lethal complication that requires immediate interruption of immunotherapy as well as corticosteroid administration. Less than 10% of the patients also develop other types of pneumonitis (OP), (e.g. infection or radiation-induced). Making the differential diagnosis of pneumonitis (IIP vs. OP) is a challenging task due to similar radiological patterns and low incidence rates. This study was performed to develop and evaluate a prediction model using handcrafted radiomic features and their associated clinical metadata to estimate the risk of IIP in patients with stage IV Non-Small Cell Lung Cancer (NSCLC) who developed pneumonitis after immunotherapy.

Impact of the COVID-19 national lockdown in the allergic rhinitis symptoms in patients treated with immunotherapy at two allergy referral centers in Bogotá, Colombia.

BackgroundCoronavirus disease‐19 (COVID‐19) “lockdowns” caused an abruptly restricted access to health care services such as immunotherapy for allergic rhinitis (AR) and led to higher exposure to indoor allergens. This study aimed to assess the impact of COVID‐19 lockdowns on AR symptoms reported by the patients treated with immunotherapy who attended the Hospital Fundación Santa Fe de Bogotá and Unidad Médico Quirúrgica de Otorrinolaringología, Colombia.MethodsPre–post study that included patients with AR confirmed diagnosis (prick test), treated with immunotherapy before and after COVID‐19 lockdowns on March–June 2020. Visual analog scales (VAS) and sociodemographic questionnaires were applied to assess AR symptoms (nasal obstruction, pruritus, rhinorrhea, and ocular symptoms) and their associated factors.ResultsA total of 318 participants were included, and their mean age was 18.9 years (SD: 12.8). The median number of immunotherapy doses applied before isolation was 11 (interquartile range [IQR]: 6–19), and the median number of immunotherapy doses missed during isolation was three doses (IQR: 2–3). Up to 38.4% of the AR patients reported that their symptoms got worse during lockdowns. A pre–post mean difference in the VAS score of 0.5 was found for nasal obstruction (p = .01), 0.7 for pruritus (p < .001), 0.7 points for rhinorrhea (p < .001), and 0.8 for ocular symptoms (p < .001). Factors associated with worsening of AR symptom scores were pet ownership, atopic dermatitis, lower educational level, and a low number of immunotherapy doses applied before lockdowns.ConclusionA large proportion of patients reported worsening of their AR symptoms, probably due to higher exposure to indoor AR allergens and interruption of immunotherapy during COVID‐19 lockdowns.

Investigating the impact of immune related adverse events, glucocorticoids use and immunotherapy interruption on long-term survival outcomes.

e14551 Background: It remains unclear whether immune related adverse events (irAEs) and glucocorticoids use could impact long term-outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). Methods: All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective multicentric study. Objectives were to assess the impact of grade 3+ irAEs, glucocorticoids use and interruption of immunotherapy on progression free survival (PFS) and overall survival (OS). Data collection was performed retrospectively using a standardized data collection form. Adverse events were categorized as irAEs based on the judgement of the treating physicians, based on the common Terminology Criteria for Adverse Events, version 4.0. Only grade 3 and more irAEs were considered in this study. As irAEs might happen late during the follow-up and progression event or death might happen early, an immortal-time bias might occur as patients responding to ICI will receive the ICI and then be exposed to irAE for a longer period of time. The first occurrence of an irAE was then included in Cox models, as a time-varying covariate. Similar methods were used to evaluate the impact of glucocorticoids introduction or ICI interruption. Results: In this 828 patients’ cohort, 78 patients presented at least one grade 3+ irAE. The first occurrence of grade 3+ irAEs had no significant impact on PFS (HR 0,94; 95%CI 0.7-1.26; p = 0,70) or OS (HR 0.82; 95%CI 0.6-1,12; p = 0,21). 65% of patients with anti CTLA4 and 55% of patients with anti PD(L)1 requested glucocorticoids, which was associated with a significant shorter PFS (adjusted HR 3.0; 95%CI 1.6-5.4; p = 0.00040) and a trend toward shorter OS. Grade 3+ irAEs led to interruption of the ICI in 82 % of patients, which was associated with a significant shorter PFS (adjusted HR 3.5; 95%CI 1.7-6.0; p &lt; 0.00043) and shorter OS (HR 4.5; 95%CI 1.7-12.1; p = 0.0027). The use of glucocorticoids was statistically associated with immunotherapy interruption. Conclusions: In our population of patients treated with single agent ICI, grade 3+ irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade 3+ irAEs reported in other studies might then be explained by the management of the irAEs.

Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Simple SummaryImmunotherapy has modified our clinical practices for the treatment of various solid cancers. Many studies have been done but it remains unclear whether adverse events induced by immunotherapy and the corticoids used for their management could impact long-term outcomes in patients treated by immunotherapy. A data collection of 828 patients was made to assess the impact of adverse events, immunotherapy interruption and the use of corticoids in long-term outcomes. In this cohort, we did not find any association between adverse events and survival outcomes. However, corticoid use was associated with a significantly shorter time before disease progression. Immunotherapy interruption was associated with a significantly shorter time before progression and survival. The impact of severe adverse events related to immunotherapy reported in other studies might be explained by their management. The use of corticoids must be careful, and resuming immunotherapy after adverse events may be important for long-term prognosis and should be considered as often as possible.It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

Pembrolizumab in MSI-high Pancreatic Sarcomatoid Carcinoma

We report the outcome of a patient with MSI-high metastatic pancreatic sarcomatoid carcinoma refractory to multiple lines of chemotherapy treated successfully with pembrolizumab. In November 2015, our patient presented with epigastric pain leading to radiologic workup. A lesion in the pancreas as well as liver metastasis were diagnosed; liver biopsy revealed a poorly differentiated sarcomatoid carcinoma. After having received every approved chemotherapy for pancreatic cancer his disease eventually progressed so that we reached out for novel therapeutic strategies. Because of the tumor being MSI high, treatment with pembrolizumab was commenced in May 2017. Clinical response with better overall quality of life was soon reported and repeated CT scans showed an ongoing partial response leading to a near complete remission in the latest scan obtained. Adverse events during the course of therapy included immune mediated arthralgia grade 1, colitis grade 2 and pneumonitis grade 1 which were managed by administration of glucocorticoids without interruption of immunotherapy. To our knowledge, this is the first case of a patient with MSI high metastatic sarcomatoid carcinoma of the pancreas successfully treated with immunotherapy for more than three years.

Novel dose-adjustment protocol for subcutaneous immunotherapy interruption

Though recommended by the practice parameters, to date, there is no standardized protocol for dose adjustment following interruption of subcutaneous immunotherapy (SCIT). Following the COVID19 pandemic, immunotherapy was stopped for all our patients (n=664) for nearly 3 months. In this study we describe the development and implementation of a novel dose adjustment protocol.

A case of durvalumab-induced lichenoid eruption evolving to bullous eruption after phototherapy: A case report

Immune checkpoint inhibitor therapy nowadays became a treatment for a wide range of cancers, and may be responsible for various dermatologic adverse effects, including bullous eruptions. In our report, we present a case of late-onset immunotherapy-induced eruption in a 62-year-old woman treated with anti-programmed cell death-L1 agent durvalumab for metastatic squamous cell carcinoma. Diagnosed as lichenoid dermatitis upon initial presentation, this eruption evolved into necrotic bullous dermatitis after several weeks of phototherapy, with histology and direct immunofluorescence study favoring lichen planus pemphigoides. Thus, this case may be regarded as durvalumab-induced lichenoid dermatitis with phototherapy-triggered progression to necrotic lichen planus pemphigoides-like eruption. The patient’s eruption responded to oral prednisone and immunotherapy interruption. Interestingly, durvalumab reintroduction in this patient led to recurrent lichenoid dermatitis without bullous component. This case of immunotherapy skin toxicity is rather distinctive by its clinical and histopathologic features, with phototherapy as an additional triggering factor.

Bullous Pemphigoid Associated with Anti-programmed Cell Death Protein 1 and Anti-programmed Cell Death Ligand 1 Therapy: A Review of the Literature.

Bullous pemphigoid constitutes a rare dermatological immune-related adverse event of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Herein, we review all published cases of anti-PD-1/PD-L1 related bullous pemphigoid and discuss current knowledge on this condition. Clinical and diagnostic findings were found to resemble those of classic bullous pemphigoid. A delayed onset of bullous pemphigoid after commencement of immunotherapy as well as a frequent precendence of a refractory pruritic eruption prior to blister development was oberved, both posing diagnostic challenges. In addition to topical and systemic treatment, most patients required either discontinuation or permanent interruption of immunotherapy. Assessment of tumour outcome did not reveal improved survival in patients developing bullous pemphigoid during immunotherapy, as suggested for other types of skin toxicity, including vitiligo. Better understanding of the pathogenetic mechanism and prognostic implications of this increasingly-reported adverse event is essential in order to establish optimal diagnostic and therapeutic management of these patients.

Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis.

e15228 Background: Immune checkpoint inhibitors (ICI) have transformed the standard care in cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal potential which lead to permanent interruption of immunotherapy. We aim to characterize ICI-mediated myocarditis and re-introduction to immunotherapy. Methods: We retrospectively evaluated the presentation, severity, and prognosis of patients diagnosed with ICI-mediated myocarditis during 2019, and presented the clinical course and outcomes of patients that were chosen for re-introduction. Results: Among seven patients, only one patient had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody (57%). All patients were treated with single agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical magnetic resonance imaging; however only 43% had reduced ejection fraction. Five patients were defined as grade I-II and two as grade III-IV. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I/II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden, while the one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and therefore therapy was interrupted permanently. Overall, survival was higher among the re-introduction patients (67% vs. 25%). Conclusions: ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life saving cancer therapy. We imply that re-introduction may be considered in low grade patients; however, better definition of the diagnosis and grading is needed.

Optimization of screening tools in patients eligible to receive immune-checkpoint inhibitors.

e14139 Background: The management of immune-related adverse events (irAEs) produced by immune-checkpoint inhibitors can be challenging, considering differences with the toxicity of classical chemotherapy. In this study, we explored the limitations in the preventions and diagnosis of irAEs at our institution and developed a strategic plan to solve them according to guidelines of the European Society for Medical Oncology and the American Society of Clinical Oncology. Methods: This is a two-phase, single center, exploratory study. In the first phase, we analyzed a random sample of 20 patients (pts) treated with nivolumab or pembrolizumab in the years 2017-2018. A Pareto chart was designed to identify issues in the baseline screening, as well as potential ways to improve the management of irAEs. After that, we implemented corrective measures based on educational lectures, early identification of patients eligible for immunotherapy, standardized protocols, and a profile of screening tests in the electronic medical records. We applied the new strategy on 15 pts treated from January-April 2019. To compare the impact of the implemented measures we used a run chart, frequencies/percentages for categorical variables, and medians/ranges for continuous variables. Adverse events were assessed according to CTCAEv5.0. Results: In the first phase, 38% of the required tests were done before the start of immunotherapy. We identified a deficit in the evaluation of cardiac and pulmonary function, chronic infections, and skin disorders. 45% of pts had some irAEs (15% G1, 15% G2 and 15% G3). Due to toxicity, 33% of pts had delays in the administration of treatment, and 11% required early interruption. After applying corrective measures, 81% of tests were requested before treatment initiation. However, screening for tuberculosis infection and echocardiogram continued to be deficient. We identified irAEs in 53% of pts (16% G1, 50% G2 and 25% G3), and 37% of them presented two or more different irAEs during the period of treatment. 37,5% and 12,5% of pts had delays or early interruption of immunotherapy, respectively. All of pts with irAEs had presented any basal alterations in screening tests. The most frequent basal alterations were found in pancreatic (66%) and thyroid activity (50%). Conclusions: Simple improvement strategies such as education programs, standardized protocols, and an electronic profile can improve the basal screening for potential irAEs. The basal alterations found in some pts can be related to the development of side effects or interactions with the immunotherapy.

EARLY STAGE Follicular Lymphoma: First Results of the FIL “Miro” Study, a Multicenter Phase II Trial Combining Local Radiotherapy and MRD-Driven Immunotherapy

EARLY STAGE Follicular Lymphoma: First Results of the FIL “Miro” Study, a Multicenter Phase II Trial Combining Local Radiotherapy and MRD-Driven Immunotherapy

Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management

There is increasing recognition of distinct inflammatory eruptions associated with checkpoint inhibitors. A better understanding of their severity, therapeutic response, and impact on cancer treatment is needed. To analyze the different rashes associated with immunotherapy referred to our institution's oncodermatology clinic and inpatient consultative service and to evaluate their therapeutic response and impact on immunotherapy. We retrospectively reviewed the medical records of patients referred to the oncodermatology clinic or inpatient dermatology service during 2016-2018 at Yale-New Haven Hospital for eruptions that developed during immunotherapy. In total, 98 patients (51 men, 47 women) treated with checkpoint inhibitors developed 103 inflammatory eruptions, with a range of mean latency of 0.2-17.7months. A minority of patients (25/103; 24.3%) required immunotherapy interruption; most of these cases involved immunobullous (7/8; 87.5%), lichenoid (8/26; 30.8%), maculopapular (6/18; 33.3%), and Stevens-Johnson syndrome-like (2/2, 100%) reactions. Only 3 of 16 (18.8%) patients who had their immunotherapy interrupted had a grade 2 or 3 flare on rechallenge. Most reactions (93/103; 90.3%) responded to dermatologic therapy or immunotherapy interruption. This was a retrospective study from a single tertiary care center. A variety of inflammatory reactions might occur from immunotherapy with differing degrees of severity. While most rashes responded to topical treatment, immunobullous and exfoliative presentations frequently interrupted immunotherapy. Increased awareness and early recognition could reduce the need for unnecessary immunotherapy interruption.

Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy

Bullous disorders associated with anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy are increasingly reported and may pose distinct therapeutic challenges. Their frequency and impact on cancer therapy are not well established. To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti-PD-1/PD-L1 therapy. We retrospectively reviewed the medical records of patients evaluated by the oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018. We identified 9 of 853 patients who developed bullous eruptions (∼1%) that were treated with an-PD-1/PD-L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. In all, 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression. This was a retrospective study from a single tertiary care center. Bullous disorders developed in approximately 1% of patients treated with anti-PD-1/PD-L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid-sparing agents.