Objective. To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes.Methods. We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available.Results. A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICImyositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection.Conclusion. ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined. PATIENTS AND METHODSPatients. We conducted a retrospective cohort study of patients seen at our institution between March 2016 and September 2019 who had received ≥1 of the following ICIs:

Currently, treatment of small bowel adenocarcinoma (SBA) mirrors that of colorectal cancer (CRC). Recent genomic data have demonstrated SBA to be a genetically unique entity, suggesting that therapies not traditionally utilized in CRC should be explored. In order to further characterize the activity of taxanes in this rare cancer, we completed a single‐center retrospective study. Twenty patients were found to have been treated with taxane‐based regimens (monotherapy in 3, combination therapy in 17). Median time to progression was 3.8 months (95% confidence interval [CI] 2.9–4.6), and median overall survival was 10.7 months (95% CI: 3.1–18.3). The results of this study demonstrate clinical activity from taxane‐based therapy in advanced SBA and support further clinical trial investigation.

Background: Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML.Methods: We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)based induction/consolidation regimen. Negative qRTPCR (CMR) was defined as fusion transcript <0.01%.Results: Thirty-one patients with CBF-AML including 14 with t(8;21) and 17 with inv(16) received parenteral DAC as maintenance therapy. Fifteen patients (48.3%) had completed FLAG-based induction/consolidation but with positive MRD (0.35%, range = 0.01%-0.91%) (Group 1). Sixteen patients (51.7%) could not complete recommended consolidations with FLAG-based regimen (due to older age or complications) and were switched to DAC maintenance (Group 2). In Group 2, eight patients (50%) had undetectable MRD (Group 2A) (all had qRTPCR ≤ 0.01%) and the other eight patients (50%) had residual fusion product by qRTPCR (0.1%, range = 0.02%-0.36%) (Group 2B) prior to starting DAC. Amongst the 23 patients who had a PCR ≥ 0.01% before maintenance therapy (Groups 1 and 2B), 12 patients (52%) attained a CMR as their best response (responders). The median pre-DAC qRTPCR amongst responders were 0.03% compared to 0.14% in nonresponders (p = .002). The median estimated molecular RFS amongst responders were 93.9 months. At a median

Background:Myositis is a rare immune checkpoint inhibitor (ICI)-related adverse event frequently associated with myasthenia gravis (MG) and myocarditis (MC) leading to mortality rates up to 52%.1Objectives:To characterize the presentation, course and outcomes of patients with ICI-related myositis alone or with overlap syndrome (myositis with MG or MC or both).Methods:We retrospectively identified a cohort of patients treated with ICI at MD Anderson Cancer Center between 2016 and 2019. Suspected myositis was identified using International Classification of Disease version 10 codes and confirmed by electronic medical record review of muscle enzymes, pathology, and other tests, when available. Patients with myositis alone or with overlap syndrome were compared using Fischer’s exact tests and t tests.Results:During the study period 8,636 patients received ICI, of which 31 (0.36%) were diagnosed with myositis: 14 (45%) with myositis alone and 17 (55%) with overlap (MG in 5, MC in 4, MG and MC in 8). Twenty patients received programmed death-1 (PD-1) or programmed death-ligand-1 (PDL-1) inhibitors, and 10 received combination PD-1/PDL-1 inhibitor with a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor. One patient received single agent CTLA-4 inhibitor (excluded from pooled data). For the entire cohort the median age at diagnosis was 69 years (range: 40-95 years); the most common presenting symptoms were fatigue in 27 (90%) patients, weakness in 24 (80%), and myalgia in 23 (77%); median CK was 2,236 U/L (range: 23-19,794 U/L). For treatment, 22 of 30 (73%) patients received at least one therapy in addition to steroids: plasmapheresis in 15 (50%) patients, intravenous immune globulin (IVIG) in 12 (40%), biologics in 9 (30%) (rituximab in 6, infliximab in 5, tocilizumab in 3), tacrolimus in 6 (20%), and mycophenolate mofetil in 4 (13%). Median length of exposure to steroids was 47 days (range: 1-250 days). Five (17%) patients were rechallenged with ICI after myositis resolution (3 with myositis alone, 2 with overlap), of which 1 (20%) patient experienced a myositis flare. Twenty-five (83%) patients were not rechallenged on ICI and 3 (12%) of those patients had a flare. Differences between patients with myositis alone compared to those with overlap are shown in Table 1. Patients with overlap more often received a second therapy, specifically plasmapheresis and IVIG, had longer hospitalizations and greater symptom burden at discharge. Overall death between groups was similar; however death attributed to the adverse event occurred only in those with overlap.Table 1.Myositis alone vs. OverlapMyositis alone(N=13)Overlap(N=17)PvalueN(%)/median days [range]Time to symptom onset42 [10-161]22 [9-149]0.234Initial steroid dose (mg/kg day)1.71.80.187Second therapy7 (54)15 (88)0.049 Plasmapheresis3 (23)12 (71)0.025 IVIG1 (8)11 (65)0.002Outcomes Hospitalization length5 [2-50]24 [7-92]0.019 Respiratory failure0 (0)13 (76) Symptoms at discharge0.047 Improved8 (62)6 (35) Resolved3 (23)1 (6)Death Overall8 (62)12 (71)0.706 Adverse event0 (0)7 (41)Conclusion:Our results represent the largest cohort of ICI-related myositis to date. Patients with overlap syndrome are treated more aggressively and have worse outcomes than those with myositis alone. Prospective studies are warranted to determine risk factors for developing myositis or overlap syndrome and to determine optimal treatment.References:[1]Anquetil BC, Salem LJ-E, Lebrun-Vignes JB, et al. Immune Checkpoint Inhibitor–Associated Myositis: Expanding the Spectrum of Cardiac Complications of the Immunotherapy Revolution.Circulation. 2018;138(7):743-745.Disclosure of Interests:None declared

e15128 Background: Data from immune checkpoint inhibitor (ICI) clinical trials show a higher incidence of ICI-related myositis with single agent ICI compared to combination therapy, but the true frequency in clinical practice is unknown. We sought to determine the incidence and clinical course of patients with ICI-related myositis at our institution. Methods: We performed a retrospective cohort study of patients treated with ICIs at MD Anderson Cancer Center between 2016 and 2019. Suspected cases of ICI-related myositis were identified using International Classification of Disease version 10 codes and confirmed by reviewing medical records, muscle enzymes and pathology. Patients treated with single agent anti-programmed death-1/ligand-1 (monotherapy) were compared to patients treated with nivolumab and ipilimumab (combination therapy) with Fischer’s exact tests, t tests, and Kaplan Meier analysis. Results: A total of 8,705 patients received ICI (7,428 monotherapy and 1,277 combination therapy), of which 31 (0.36%) were diagnosed with myositis. Estimated incidence of myositis was 0.28% and 0.78% (p=0.004), in the monotherapy and combination therapy groups, respectively. One patient was treated with ipilimumab alone (excluded from pooled data). Overall median age was 69 years (range: 40-95) with median follow up of 4 months after presentation for myositis. Thirteen (43%) patients had myositis alone and 17 (57%) had overlap with myasthenia gravis or myocarditis or both. After myositis resolution, 5 (17%) patients were rechallenged on ICI, of which 1 (20%) patient experienced a myositis flare. Differences between combination and monotherapy are summarized in the table. Patients treated with combination had shorter time to symptoms, but similar symptom grade at presentation, median length of hospitalization, and initial tumor response, compared to patients given monotherapy. Median overall survival (OS) was longer in combination vs monotherapy. Conclusions: Patients receiving combination ICI therapy had higher incidence of myositis with earlier onset than monotherapy; however, no differences in cancer outcomes or hospitalizations were observed between groups. Creation of multi-center databases are needed to develop treatment guidelines for ICI-related adverse events that will improve outcomes. [Table: see text]