BACKGROUND:With the shift to immunotherapy (IO) in first-line (1L) treatment for patients with advanced non-small cell lung cancer (aNSCLC), this study aims to describe second-line (2L) treatment patterns and outcomes. METHODS:This retrospective study examined 2L outcomes in patients with stage IIIB-IV, epidermal growth factor receptor (EGFR)-/anaplastic lymphoma kinase (ALK) wild-type aNSCLC who started 1L therapy between 2016 and 2019 and received subsequent 2L therapy. Follow-up continued through November 2020. Subgroups included: 2L IO, 2L non-IO, and IO re-challenge (1L and 2L). RESULTS:A total of 194 patients initiated 2L therapy; 93 received IO (12 also in 1L), and 101 did not. For IO and non-IO, respectively: overall response rate (ORR) was 28.0% and 25.7%; median follow-up was 23.7 and 20.0 months; median realworld progression-free survival (rwPFS) was 8.4 and 5.1 months (p = 0.0006); median overall survival (OS) was 13.5 and 7.7 months (p = 0.0021). No deaths occurred in the IO re-challenge cohort after a median follow-up of 35.0 months. CONCLUSIONS:rwPFS and OS were consistent with clinical trials of 2L IO regimens. The few patients who received IO in 1L and 2L had favorable rwPFS and OS. Future research on sequential IO therapies in 1L and 2L aNSCLC is warranted.

Real-world patient characteristics and outcomes were assessed in 150 patients with intermediate- or highrisk primary myelofibrosis (MF) who received fedratinib (a Janus kinase 2 inhibitor) following ruxolitinib failure. Fedratinib was associated with significant reductions in spleen size and reported number of MF-related symptoms, illustrating the benefit of fedratinib following ruxolitinib discontinuation. Background: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice. Patients and Methods: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. Results: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved >= 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01). Conclusion: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

OBJECTIVES:Recent advances have created options for first-line (1L) treatment of advanced/metastatic non-small cell lung cancer (aNSCLC). The study objectives were to describe the utilization of 3 classes of 1L treatment-chemotherapy (CT), immunotherapy (IO), and chemoimmunotherapy (IO+CT)-and the total, third-party payer, direct health care costs.STUDY DESIGN:Retrospective, administrative claims database analysis of patients with aNSCLC who initiated 1L treatment between January 1, 2017, and May 31, 2019, with IO, CT, or IO+CT.METHODS:Microcosting enumerated health care resource utilization, including antineoplastic drug costs, using standardized costs. Generalized linear models estimated per-patient per-month (PPPM) costs during 1L treatment, and adjusted cost differences in 1L among treatment cohorts were calculated using recycled predictions.RESULTS:A total of 1317 IO-, 5315 CT-, and 1522 IO+CT-treated patients were identified. Utilization of CT declined from 72.3% to 47.6% between 2017 and 2019, replaced by use of IO+CT, which increased from 1.8% to 29.8%. Total PPPM costs in 1L were highest with IO+CT at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT vs IO cohort (P < .001) and IO costs were $1024 (95% CI, $67-$1980) lower than CT (P = .04).CONCLUSIONS:IO+CT accounts for almost one-third of 1L aNSCLC treatment modalities, coinciding with a reduction in treatment with CT. Costs for patients treated with IO were lower than those for patients treated with both IO+CT and CT alone, driven primarily by antineoplastic drug and associated medical costs.

e18896 Background: Since 2017, 6 CAR-t therapies have been approved to treat pediatric and adult hematologic malignancies (HM). Due to the complexity of administration and severe toxicity including cytokine release syndrome (CRS), CAR-t is usually administered in an inpatient setting. We sought to provide the first pan-cancer, U.S. based analysis of duration of hospitalization during CAR-t overall and for patients who experience CRS. Methods: Patients were identified from a large, US based EMR database including more >40M patients, >500 hospitals and 30 healthcare systems including both community/academic health systems. Patients with ≥1 procedure code for general administration of CAR-t therapy (e.g.: XW033C3, introduction of engineered autologous chimeric antigen receptor t-cell immunotherapy into peripheral vein) or a specific approved CAR-T (XW033K7, introduction of idecabtagene vicleucel immunotherapy into peripheral vein) between 2017 and 2022 and a diagnosis of a HM were selected. CRS was identified as the presence of any ICD-10 diagnosis code of D89.83X post-administration. Time from the date of CAR-t administration to hospital discharge was calculated overall, by cancer type, and for patients with and without a confirmed diagnosis of CRS. Results: A total of 212 patients (multiple myeloma [MM] = 64, b-cell lymphoma = 77, follicular lymphoma = 47, mantle cell lymphoma [MCL] = 13, acute lymphoblastic leukemia = 11) meeting selection criteria were identified. Cohort characteristics are shown in Table 1. Median duration of hospitalization was 12 days (range 1-56); shortest at 10 days for MM and longest at 15 days for MCL. Mean duration of hospitalization decreased slightly from 12.3 days (sd = 11) for patients treated in 2019 or earlier to 11.9 days (sd = 4.2) for patients treated in 2022 Median duration of hospitalization for patients with a CRS diagnosis (n = 100) was 12 (range 1-30) versus 11 days (range 1-56) for those without CRS (n = 112). Conclusions: CAR-t poses a unique set of administrative, logistical and clinical challenges. This study provides the first contemporaneous estimates of the length of hospital stays during CAR-t infusion which was found to be 12 days. Differences in length of hospitalizations did not decline significantly over time or were significantly different between those with and without CRS however further research to examine health system factors and patient factors (i.e., severity of CRS) are needed. [Table: see text]

Talazoparib was approved by the FDA for use in adult patients with germline BRCA mutated HER2-negative breast cancer based on results from the EMBRACA trial. This article reports the results of a study conducted in the real-world in a U.S. population. Background Talazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting. Patients and Methods Characteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics. Results Among 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of >= 2 and 19.0% had brain metastasis. Mutations in gBRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS >= 2 at talazoparib initiation were associated with treatment failure and progression or mortality. Conclusion Overall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA.

Abstract Introduction/Objective Myeloid/lymphoid neoplasms (MLN) with fibroblast growth factor receptor 1 gene (FGFR1) rearrangement (MLNFGFR1) is a rare and aggressive hematologic malignancy characterized by molecular disruption of FGFR1 at the 8p11 locus. This real-world study describes demographic and clinical characteristics, diagnostic testing, and clinical outcomes in patients with MLNFGFR1 in the US. Methods/Case Report Probable MLNFGFR1 cases (n=51) were identified from a retrospective, physician-abstracted (5/29/2020-6/23/2020) chart review of patients within the US Cardinal Health Oncology Provider Extended Network (feasibility survey). In a subsequent full chart review (12/29/2020-3/4/2021), 33 of these probable MLNFGFR1 cases were considered to be confirmed based on additional 8p11/FGFR1 testing result data collected. Descriptive analyses of demographic/clinical characteristics, diagnostic testing, and clinical outcomes of patients with confirmed MLN FGFR1 were performed. Results (if a Case Study enter NA) The mean age at initial MLNFGFR1 diagnosis was 65.9 (SD 13.5) years, 60.6% patients were male, and 63.6% were white. Patients were managed by 12 physicians,10 in community practices. FGFR1 translocations were identified by karyotyping in 72.7% of patients. Rearrangements in FGFR1 were detected by fluorescence in situ hybridization, next generation sequencing, and/or real-time polymerase chain reaction in 66.7%, 21.2% and 6.1% of patients, respectively. FGFR1 rearrangement was detected in bone marrow aspirate and peripheral blood in 90.9% and 9.1% of patients, respectively. Fusion partners ZMYM2 and CPSF6 were reported in 46.2% and 15.4% of patients, respectively, and BCR, CUX1, RANBP2, TPR, and MYO18A were reported in 7.7% of patients each. Conclusion Although rare, patients with MLNFGFR1 do present in US community practice settings. Conventional cytogenetics can identify FGFR1 translocations which can be confirmed by FISH with FGFR1 break-apart probes. NGS can be used to identify cryptic rearrangements when clinical suspicion is high but no rearrangement is present on FISH. In addition to diagnosis, RT-PCR is also useful to assess molecular response.

e18891 Background: CAR-T therapy represents the most significant advancement in the treatment of HM in the past 5 years. Life-threatening complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may occur leading to significant morbidity and mortality. We aimed to describes the frequency of CRS and ICANS and the time to onset of each post CAR-T therapy administration in real-world, U.S. patients. Methods: Patients (pts) with HM who received any FDA-approved CAR-T therapy were identified from a U.S. EMR database containing de-identified healthcare data for > 40M patients from > 500 hospitals and 30 healthcare systems (including academic centers). Confirmation of CAR-t treatment was based on ≥1 procedure code for general administration of CAR-T therapy (e.g., XW033C3, introduction of engineered autologous chimeric antigen receptor t-cell immunotherapy into peripheral vein) or a specific approved CAR-T (I.e., XW033K7, introduction of idecabtagene vicleucel immunotherapy into peripheral vein) between 2017 and 2022. Diagnosis of CRS or any ICAN was based ≥1 related ICD-10 diagnosis code (e.g., CRS = D89.83X). Frequency of occurrence of CRS, symptoms of CRS, ICANS symptoms, and severity of CRS or ICANS is described (severity based on validated clinical algorithm). Time to CRS and ICANS was calculated as the interval from CAR-T administration to first reported diagnosis, respectively. Results: 212 pts met the study criteria including 77 b-cell lymphoma, 64 multiple myeloma, 47 follicular lymphoma, 13 mantle cell lymphoma and 11 acute lymphoblastic leukemia pts. The majority were male (54.7%); median age was 60 years. Overall, 100 (47.2%) pts were diagnosed with CRS (any grade) while 82 (38.7%) pts experienced any ICAN symptoms. The top three CRS symptoms were fever (57.5%), hypotension (31.1%) and tachycardia (21.2%). The top three ICANS symptoms were obtundation (18.4%), confusion (12.7%), and delirium (12.7%). Of CRS pts, 25.0% experienced severe symptoms, including renal insufficiency (10.0%), atrial fibrillation (9.0%), ventricular tachycardia (7.0%), and cardiac failure (2.0%). The median time to development of CRS was 2 days (range 0-23 days). Of pts. experiencing ICANS, 72.0% experienced any mild symptom and 53.7% experienced any severe symptom, including obtundation (47.6%), aphasia (13.4%), and seizures (1.2%). The median time to development of ICANS post CAR-T therapy was 6 days (range 0-26 days). Conclusions: Our study is the first real-world, U.S. evaluation of the frequency and time to toxicities associated with CAR-t therapy across multiple hematologic malignancies. While well-described in RCTs these data highlight the need for the continued development of clinical and therapeutic approaches to minimize their impact on the effectiveness of CAR-T.

Introduction: Diabetic gastroparesis (DGP) is a chronic disorder marked by significant morbidity and healthcare utilization. DGP patients experience 3x greater emergency department (ED) and inpatient hospitalization (IH) costs, and 2x greater hospital outpatient (HO) costs compared to patients with diabetes without GP. Nasal metoclopramide (NMCP) was approved in 2020 for acute and recurrent DGP. We sought to compare real-world healthcare costs (from a US, third-party payer perspective) between patients treated with NMCP vs oral MCP (OMCP) to assess if an alternate route could improve outcomes. Methods: NMCP and OMCP treated DGP patients were retrospectively identified in the IBM MarketScan Research Database. Patients ≥18 years dispensed NMCP or OMCP between June 2020 and December 2022, with ≥6 months of pre-index (dispense date) and post-index data were selected. Using the near-neighbor method of propensity score (PS) matching, 4 OMCP patients were selected for every 1 NMCP patient. Total costs (medical and pharmacy) during the 6 months following treatment initiation were calculated for each cohort along with total costs by setting of care: IH, ED, HO, physician office (PO), clinic, lab/home/telehealth (LHT). Mean differences in cost along with 95% confidence internal (CI) were obtained using Tweedie generalized linear model (GLM) with Gamma distribution and identity link. Results: Forty-five NMCP patients were matched to 180 OMCP patients across demographic and disease severity, with standardized mean differences <0.10. NMCP-treated patients incurred lower cost across care sites: IH = -$10,021 (95%CI: -17,666, -2,376; P-value=.01), ED = -$926 (-1,371, -481; P-value< .001), HO= -$3,247 (-5,428, -1,066; P-value=.004), and LHT = -$472 (-846, -98; P-value =.014). Total medical cost (sum of all sites) was $16,808 (8,196, 25,420; P-value< .001) lower in the NMCP cohort. NMCP pharmacy cost was $1,581 (-1,269, 4,431) higher, but not statistically significant (P-value=0.276). Total healthcare cost was $15,227 lower in NMCP versus OMCP cohort (4,615, 25,839; P-value=.005). Conclusion: Total all-cause healthcare cost and specifically for inpatient, outpatient and ED visits were significantly reduced during the 6 months following treatment initiation with NMCP compared to OMCP confirming the superiority of the NMCP route for treating DGP patients. We observed similar results for DGP symptom-related outcomes.

Background: With advanced or metastatic non-small cell lung cancer (aNSCLC) being treated with immunotherapy (IO) in first line, little data exists on treatment patterns and outcomes in second line (2L), which this study describes.Methods: This retrospective, multisite cohort study examined outcomes in 2L with and without prior IO treatment, using data for patients with stage IIIB-IV, EGFR-/ALK wild-type aNSCLC who initiated 1L therapy from 01/01/2016-12/31/2019 and initiated 2L therapy following disease progression. Three subgroups included: 1) 2L IO, 2) 2L non-IO, and 3) 1L and 2L IO (IO rechallenge- a subgroup of cohort 1). Demographics, clinical characteristics, treatment patterns, disease response, and overall survival (OS) were collected. Overall response rate (ORR) per line of therapy (LOT) was guided by RECIST v1.1. Real-world progression-free survival (rwPFS) and OS were calculated from 2L initiation.Results: 194 initiated 2L. 93 received 2L IO (12 received IO in 1L and 2L) and 101 did not. ORR was 28.0% for 2L IO and 25.7% for non-IO. Median follow-up was 23.7 months for 2L IO and 20.0 months for non-IO. Median rwPFS was 8.4 months for 2L IO and 5.1 months for 2L non-IO. Median OS was 13.5 months for IO and 7.7 months for non-IO. In the 1L and 2L IO cohort, no deaths occurred after a median follow-up of 35.0 months.Conclusions: rwPFS and OS were consistent with PFS and OS in clinical trials of 2L IO regimens. Those few who received IO in 1L and 2L had favorable rwPFS and OS.

Background: Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLNFGFR1), also known as 8p11 myeloproliferative syndrome, is an aggressive hematologic malignancy comprising a range of presentations that share a characteristic FGFR1 rearrangement at the 8p11 locus. Currently, 16 known FGFR1 fusion partners account for the phenotypic diversity. Presentations include bone marrow (BM) involvement by chronic phase myeloid disease or blast phase (BP) myeloid, lymphoid, or mixed lineage disease, which may be accompanied by extramedullary BP disease; patients (pts) may also have extramedullary involvement only. 8p11 translocations are usually detected by karyotyping, and FGFR1 rearrangement is confirmed with fluorescent in situ hybridization (FISH) using break-apart probes for FGFR1. FGFR1 rearrangements may also be detected with next-generation sequencing (NGS) or real-time polymerase chain reaction (RT-PCR). Eosinophilia is not required for diagnosis, but its presence can be a diagnostic clue. MLNFGFR1 is associated with poor clinical outcomes, with allogeneic stem cell transplant (ASCT) the only potential cure. This real-world study describes baseline characteristics, treatment patterns, and clinical outcomes of 33 confirmed cases in US community practices. Methods: This was a retrospective, multisite, physician-abstracted chart review conducted in 2 phases within the Cardinal Health Oncology Provider Extended Network (OPEN; data collection: phase 1, 5/29/2020-6/23/2020; phase 2, 12/29/2020-3/4/2021). Eligible pts had to be ≥18 y old at diagnosis; diagnosed with myeloproliferative neoplasm (MPN) unclassified, myelodysplastic syndrome (MDS)/MPN, precursor T- or B-cell lymphoblastic leukemia/lymphoma, post-MPN acute myeloid leukemia (AML), or mixed-phenotype acute leukemia; had BM results available and cytogenetic testing performed. In phase 1, physicians abstracted medical records from eligible pts. Cases were considered probable MLNFGFR1 if physicians reported detection of an FGFR1-associated translocation and/or FGFR1 rearrangement. In phase 2, demographic/clinical characteristics, treatment, outcomes, and diagnostic/genetic testing results of probable cases were collected. Based on data abstracted from karyotyping, break-apart FISH testing, NGS, and/or RT-PCR testing reports, a subset of probable cases was confirmed as MLNFGFR1. Cases with inconclusive tests and/or without detection of an 8p11 translocation or FGFR1 rearrangement were excluded. Results: 560 cases with myeloid/lymphoid malignancies were reviewed and 51 probable cases were identified in phase 1. Among probable cases, 33 pts managed by 12 physicians were confirmed as MLNFGFR1 in phase 2. Among the 33 confirmed cases, mean (SD) age at initial MLN diagnosis was 65.9 (13.5) y; 60.6% were male; 63.6% were White, 18.2% Asian, and 15.2% Black. FGFR1-associated translocations were detected by karyotyping in 72.7% of pts and FGFR1 rearrangement was detected by break-apart FISH, NGS, and/or RT-PCR in 66.7%, 21.2%, and 6.1% of pts, respectively. Rearrangement was detected in BM aspirate in 90.9% of pts and in peripheral blood in 9.1%. The most commonly reported partner fusion gene was ZMYM2, observed in 18.2% of pts. Median (IQR) follow-up since MLN diagnosis was 11.7 (7.9-26.6) mo. Overall, 97.0% of pts initiated therapy, 96.9% of whom received a total of 1 line of therapy at last encounter. Median (IQR) time from initial diagnosis to treatment initiation was 1.9 (1.0-3.0) wk; median (IQR) duration of first-line therapy was 33.4 (23.5-42.1) wk. Only 3 pts underwent ASCT; one had disease relapse after 54.4 wk. Disease progression/transformation to AML was reported in 1 of 18 pts with initial MPN unclassified or MDS/MPN diagnoses. Among 23 pts alive at last encounter, 69.6% remained on active therapy, 17.4% had received palliative treatment, and 8.7% were in remission. Among 10 pts who were deceased at end of study, median (IQR) survival from initial MLN diagnosis was 8.3 (5.4-9.2) mo. Conclusions: This retrospective chart review demonstrated that, although MLNFGFR1 is rare, pts with this malignancy will present in US community practice settings. As effective targeted therapies become available, this diagnosis should be considered in pts with congruent presentations and 8p11 translocations on conventional cytogenetics and/or evidence of FGFR1 rearrangement on other molecular testing.

Purpose:Most patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with a complement protein 5 (C5) inhibitor achieve full control of terminal complement activity and intravascular hemolysis. The minority remains anemic and transfusion dependent despite this control. Etiology for ongoing anemia is multifactorial and includes bone marrow failure, breakthrough hemolysis, extravascular hemolysis (EVH) and nutritional deficiencies.Patients and Methods:To evaluate the potential etiologies of hemoglobin levels <10 g/dL despite receiving C5 inhibitor therapy, we performed a retrospective US chart review of adult patients with PNH and treated for at least 12 months with eculizumab (n=53), ravulizumab (n=32), or eculizumab followed by ravulizumab (n=15). Clinically evident EVH was defined as at least one transfusion, reticulocyte count ≥120×109/L and hemoglobin level ≤9.5 g/dL. Safety data were not collected. Mean treatment duration was 26.5±17.2 months.Results:Treatment with C5 inhibitors significantly improved hemoglobin, lactate dehydrogenase, and number of transfusions versus baseline. Among the patients with hemoglobin <10 g/dL during the last 6 months of treatment (n=38), one patient (eculizumab) had clinically evident EVH, and 10 patients had active concomitant bone marrow failure. Bone marrow failure was a major contributor to hemoglobin <10 g/dL and transfusion dependence; clinically evident EVH was uncommon.Conclusion:A range of hematologic causes need to be considered when evaluating anemia in the presence of treatment with a C5 inhibitor.

1036 Background: Trastuzumab Deruxtecan (T-DXd) was associated with an increased risk of interstitial lung disease (ILD)/pneumonitis (P) in metastatic breast cancer (mBC) patients (pts) in clinical trials, leading to ILD/P monitoring and management guidelines in the product label. This study aims to describe the monitoring and management of ILD/P during T-DXd therapy among US community oncology practices. Methods: Oncologists in the Cardinal Health Oncology Provider Extended Network (OPEN) participated in a cross-sectional survey on monitoring approaches for ILD/P among mBC pts. Participating physicians provided data from medical charts of up to 10 pts who were treated with T-DXd regarding presence of ILD/P symptoms, management, and outcomes of ILD/P symptoms. Results: Twenty-eight physicians from across the U.S participated and provided data on 149 T-DXd pts. Nearly all physicians reported they were monitoring ILD/P after T-DXd initiation by physical examination (n = 27), symptoms checklist (n = 25) and pulse oximetry (n = 23) at every visit, whereas fewer reported performing lung CT scan (n = 18), echocardiogram (n = 13), chest X-ray (n = 12), lung PET scan (n = 10), pulmonary function tests (n = 8) and diffusion testing (n = 7) on a less frequent basis. Among 149 T-DXd pts, 4 pts were diagnosed with ILD/P over an average T-DXd treatment duration of 5.5 months. All 4 cases initiated T-DXd treatment at 5.4mg/kg every 3 weeks, experienced ILD/P within the first 5 cycles of T-DXd, were diagnosed with lung CT scan and initially presented with Grade 2 symptomology (2 cases progressed to Grade 3). For both cases that remained as Grade 2, ILD/P completely resolved within 23 days. One case received IV methylprednisolone (1000mg daily; duration of therapy (DOT): 3 days) during hospitalization, oxygen therapy and T-DXd was permanently discontinued; whereas the other one received oral prednisone (started at 40mg daily and tapered to 5mg daily; DOT: 7 days) and T-DXd dose was held. For the two grade 3 cases, one received IV methylprednisolone (125mg daily; DOT: 7 days) during hospitalization, T-DXd dose was held, and ILD/P completely resolved within 11 days; whereas the other case received oral prednisone (started at 80mg daily and tapered to 5mg daily; DOT: 63 days), oxygen therapy, T-DXd was permanently discontinued, and ILD/P resolved with sequela within 46 days. Conclusions: ILD/P incidence in this small study sample of patients receiving T-DXd treatment was 2.7%. Although general awareness of ILD and routine screening by pulse oximetry and physical exam were common, management approaches for ILD/P were not always consistent with T-DXd prescribing information. Further physician education may be needed to improve appropriate management of ILD/P and outcomes for T-DXd pts.

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57-391, OPEN) and 110 (37-148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54-553) and 166 (108-262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.

311 Background: The immuno-oncology (IO) therapy combination nivolumab + ipilimumab, and the IO-tyrosine kinase inhibitor (TKI) combination pembrolizumab + axitinib, received US FDA approvals in 2018 and 2019, respectively, as first-line (1L) therapy for advanced renal cell carcinoma (aRCC). We examined physician perceptions of concerns about and barriers to 1L treatment by class of regimen (IO-IO, IO-TKI, and single-agent TKI [SA-TKI]) in the United States. Methods: US-based oncologists treating ≥ 5 aRCC patients in the prior 12 months were identified from the Cardinal Health network, a community of > 800 oncologists. Physicians were surveyed about concerns in prescribing and barriers to treating by class (scale of 1–5; 1 = no concern/not a barrier, 5 = most concerning/major barrier); mean scores are reported. Adverse events (AEs) of concern were selected from a prespecified list and respondents rank-ordered from most to least concerning by class. Physicians were also asked to gauge affordability and to rank-order 13 characteristics to identify key factors in prescribing preference. The impact of COVID-19 on aRCC care in practice was also assessed. Results: A total of 49 providers (84% community, 16% academic) treating a median of 20 (IQR 14–30) aRCC patients from across the United States participated. For IO-IO, the top 3 concerns in prescribing were AEs (4.3), patient out-of-pocket costs (OOP; 3.7), and unexpected late AEs (3.6), whereas patient OOP (4.3), AEs (4.1), and patient adherence (3.9) were of most concern for IO-TKI. For SA-TKIs, the top 3 concerns were patient adherence (3.9), patient OOP (3.9), and AEs (3.6). High patient OOP and impact on quality of life were the top 2 barriers in using IO-TKI therapy. The most concerning AEs were colitis, pneumonitis, and hypertension for IO-IO or IO-TKI, and diarrhea, fatigue, hand-foot syndrome, and hypertension for SA-TKI. Overall survival (OS), progression-free survival (PFS), and complete response (CR) were ranked 1st, 2nd, and 3rd factors in prescribing preferences while patient compliance, patient preference, and practice reimbursement ranked 11th, 12th, and 13th. Patient OOP and drug acquisition costs (DAC) were the most important factors when considering the affordability of treatment, with the perception that IO-IO was the most expensive among the classes of therapy. The overall impact of COVID-19 on caring for aRCC patients was very limited, with a moderate increased use of telemedicine and a slight impact on the timing and number of routine care visits. Conclusions: OS, PFS, and CR ranked highest among the most important factors influencing selection of 1L treatment for aRCC. Factors of concern and barriers varied by class of treatment, with patient adherence and OOP affecting use of TKI or IO-TKI therapies, and AEs affecting the use of IO-based therapy. This study revealed perceptions of high patient OOP and DAC of IO-IO therapy, in contrast to our expectations.

OBJECTIVES:Antiviral treatments for early intervention in patients with mild-to-moderate COVID-19 are needed as a complement to vaccination. We sought to estimate the impact on COVID-19 cases, deaths, and direct healthcare costs over 12 months following introduction of a novel, antiviral treatment, RD-X19, a light-based, at-home intervention designed for the treatment of mild-to-moderate COVID-19 infection. METHODS:A time-dependent, state transition (semi-Markov) cohort model was developed to simulate infection progression in individuals with COVID-19 in 3 US states with varying levels of vaccine uptake (Alabama, North Carolina, and Massachusetts) and at the national level between 1 June 2020 and 31 May 2021. The hypothetical cohort of patients entering the model progressed through subsequent health states after infection. Costs were assigned to each health state. Number of infections/vaccinations per day were incorporated into the model. Simulations were run to estimate outcomes (cases by severity, deaths, and direct healthcare costs) at various levels of adoption of RD-X19 (5%, 10%, 25%) in eligible infected individuals at the state and national levels and across three levels of clinical benefit based on the results from an early feasibility study of RD-X19. The clinical benefit reflects a decline in the duration of symptomatic disease by 1.2, 2.4 (base case), and 3.6 days. RESULTS:In the base case analysis with 10% adoption, simulated infections/deaths/direct healthcare costs were reduced by 10,059/275/$69 million in Alabama, 21,092/545/$135 million in North Carolina, and 16,670/415/$102 million in Massachusetts over 12 months. At the national level, 10% adoption reduced total infections/deaths/direct healthcare costs by 686,722/17,748/$4.41 billion. CONCLUSION:At-home, antiviral treatment with RD-X19 or other interventions with similar efficacy that decrease both symptomatic days and transmission probabilities can be used in concert with vaccines to reduce COVID-19 cases, deaths, and direct healthcare costs.

Background: Relief of symptoms and splenomegaly is an important treatment (Tx) goal for patients with myelofibrosis (MF). Fedratinib (FEDR) and ruxolitinib (RUX) are approved in the USA for Intermediate (Int)- or High-risk (HR) primary or secondary MF. Aims: To describe spleen size, and hematologic and MF-specific symptoms, during the first 6 months of FEDR therapy after prior Tx with RUX in US clinical practices. Methods: Adults with Int- or HR MF who initiated FEDR on or after August 16, 2019 (FEDR approval date) and with ≥90 days of follow-up were identified from community oncology practices. Eligible patients were those treated with RUX and then FEDR, who had spleen palpation at FEDR initiation, and who had completed ≥1 cycle of FEDR. Treating physicians completed electronic case report forms for the selected eligible patients, extracting patient characteristics, Tx pattern data, and clinical outcomes such as spleen size, MF-related symptoms per the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0), hemoglobin (Hb), and platelet and white blood cell (WBC) counts, at each visit in the first 6 months of FEDR Tx. Data were collected from February to March 2021. Mean spleen size, symptom count, Hb, and platelet and WBC counts at FEDR initiation vs at 3 and 6 months post-FEDR were compared via paired 2-sided t-test. Percentage reduction in spleen size and proportion of transfusion-dependent patients between FEDR initiation and 3 and 6 months post-FEDR were compared via 1-sided chi-square test. Only patients assessed at FEDR initiation (with palpable spleen or complete blood count available) and with a corresponding assessment at 3 or 6 months were included in the comparative analysis. Results: Among 150 eligible patients, the mean age at FEDR initiation was 68 years (range, 36–85). Median duration of RUX Tx prior to FEDR was 7.6 months (range, 0.7–65.5). At FEDR initiation, MF risk was categorized as International Prognostic Scoring System (IPSS)/Dynamic IPSS HR in 43% of patients, Int-2 in 37%, Int-1 in 9%, and unknown in 10%. A total of 74% of patients started FEDR at the recommended dosage of 400 mg daily. Median duration of post-FEDR follow-up was 5.1 months (IQR, 3.0–17.3) for patients initiated at FEDR 400 mg daily and 4.4 months (IQR, 3.0–14.3) for those initiating at <400 mg daily. At data cutoff, 55% of patients were still on FEDR. The primary reason for FEDR discontinuation was disease progression (43%). Mean duration of FEDR Tx was 4.7 months. Of 67 patients who discontinued FEDR, 44 were deceased at data cutoff. At FEDR initiation, 88% of patients had palpable spleen; mean spleen size was 16.0 cm (standard deviation [SD] 5.8) above the costal margin, which decreased to 13.2 cm (SD 7.9) at 3 months (P=0.0001) and 7.2 cm (SD 7.4) at 6 months (P=0.012). Mean number of MF-related symptoms declined significantly at 3 and 6 months; mean platelet count increased significantly at 6 months, from 160×109/L to 186×109/L (Table). Overall, 65.2% of patients experienced spleen size reduction, 18.8% had no change, and 16.0% had an increase. Mean best percentage change in spleen size was −29.2% (median −9.8%); complete resolution of palpable spleen occurred in 21% of patients. Image:Summary/Conclusion: This study illustrates the real-world effectiveness of FEDR after RUX failure in patients with Int- or HR MF. FEDR provided significant reductions in spleen size and reported number of MF-related symptoms after 3 months of Tx, including complete spleen responses. Greater benefits were observed with longer Tx duration.

Background: Treatment for recurrent or advanced/metastatic non-small cell lung cancer (aNSCLC) has advanced in the past 5 years with immunotherapy (IO). This study sought to describe first-line (1L) aNSCLC treatment patterns and clinical outcomes. Methods: In this retrospective, multisite cohort study, community oncologists reported data for randomly selected stage IIIB/IV, EGFR-/ALK wild-type aNSCLC patients who initiated 1L systemic therapy from 01/01/2016 to 12/31/2019. Follow-up was through November 2020. Demographics, clinical characteristics, treatment patterns, disease response, progression, and death/last follow-up date were described. Overall response rate (ORR) was calculated using tumor measurements applying RECIST v1.1 guidelines. Progression-free survival (PFS) and overall survival (OS) were calculated from 1L initiation by Kaplan-Meier method. Results: 497 patients from 46 sites were included. The most common 1L regimens (%) were platinum-doublet chemotherapy plus IO (PDC+IO) (40.6%), PDC (29.4%), IO monotherapy (20.7%), and PDC+bevacizumab (6.2%). From 2016 to 2019, 1L PDC declined from 63% to 10%, whereas 1L PDC+IO increased from 14% to 58%. The ORRs were 64.9%, 32.9%, 60.2%, and 61.3% for 1L PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab, respectively. Median 1L PFS/OS (months) was 15.6/26.5, 5.3/13.7, 17.8/not reached, 10.8/18.6, respectively, for PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab. Among patients who received only 1L treatment (n = 299), 41.5% had no further therapy and were deceased. Conclusions: Although the 1L treatment paradigm has recently shifted to IO-based regimens, 41.5% did not survive past 1L. Median 1L PFS did not exceed 1.5 years and median OS remained limited across all 1L treatment groups, illustrating continued unmet aNSCLC therapeutic needs.

e19065 Background: ESAs are used in first-line treatment for symptomatic or transfusion-dependent anemia in patients (pts) with LR-MDS. Ultimately, the majority of pts with LR-MDS who receive an ESA will experience ESA treatment failure. This real-world (RW) study aims to describe pt characteristics, treatment patterns including ESA use, and outcomes in pts with LR-MDS. Methods: A retrospective, observational, US multisite, cohort chart review of adult pts diagnosed with LR-MDS between January 1, 2015 and June 24, 2020 was conducted. Eligible pts had not received luspatercept or participated in a clinical trial and had ≥ 1 year of follow-up after LR-MDS diagnosis, unless follow-up was < 1 year due to death during this interval. Demographics, clinical characteristics, treatment patterns, and outcomes were summarized using descriptive statistics. Median duration of therapy (DOT) was estimated using the Kaplan-Meier method. Results: Among 338 eligible pts, median age at LR-MDS diagnosis was 70 years (range: 19–100), 55% were female, 71% were White, 17% had known detection of del(5q), and ring sideroblast status was known to be positive for 7%. Transfusion independence within the 8 weeks prior to diagnosis (TI8) was reported for 48% of eligible pts and 17% had intermediate-1/ intermediate disease risk by IPSS/ IPSS-R risk classification. Within the study follow-up time (median of 28.3 months from diagnosis), 76% of pts had received systemic therapy for MDS (median DOT: 29.2 months). An ESA was used in 56% (n = 190) of pts, of whom 38% received red blood cell (RBC) transfusions during ESA treatment. Of those receiving systemic treatment for LR-MDS, 11% were hospitalized for reasons that physicians reported were related to MDS treatment complications. At the time of data collection, 30% of pts had died. Among 38 pts determined to have failed ESA treatment by abstracting physicians, 11% had TI8, 34% had intermediate-1/ intermediate disease risk, 82% received RBC transfusions during ESA treatment, 26% required hospitalization that abstracting physicians reported was related to MDS treatment complications, 32% continued to receive ESA post-failure, and 53% were deceased at data collection. Conclusions: Results from this RW study indicate that a higher proportion of pts with LR-MDS who experienced ESA treatment failure according to abstracting physicians had intermediate-1/ intermediate disease risk at diagnosis, were transfusion dependent at diagnosis, required RBC transfusions during ESA treatment, were hospitalized for reasons related to MDS treatment complications, and had poor short-term survival. Nearly a third of pts who experienced ESA treatment failure still received an ESA after initial failure. In summary, findings from this study indicate that pts with LR-MDS who experience ESA treatment failure are likely to have worse outcomes.

Aim: To demonstrate the efficacy of pomalidomide for relapsed/refractory multiple myeloma (RRMM) following treatment in real-world, community practice using retrospective database analysis. Materials & methods: US-based community oncologists identified patients with RRMM treated with or without pomalidomide following first-line lenalidomide. Disease response (≥ very good partial response) and progression-free survival were compared. Results: Disease response was 78.6 and 51.7% for pomalidomide (n = 126) and nonpomalidomide cohorts (n = 174), respectively (p < 0.0001). Multivariate adjusted odds of response were 4.5-times greater for pomalidomide cohort (p < 0.0001). Median progression-free survival was not reached for pomalidomide cohort and 16.7 months for nonpomalidomide cohort (log-rank p < 0.01). Conclusion: Following lenalidomide induction in RRMM, pomalidomide is an effective treatment.