2nd Line Therapy Research Articles

P40.16 Real-World Data and Racial Outcomes for NSCLC in The Chemo-Immunotherapy Era

Lung cancer remains the leading cause of cancer death among both men and women. Recent pivotal trials established combination chemo-immunotherapy (IO) as the standard of care for advanced non-small cell lung cancer (NSCLC) without any targetable mutations. Unfortunately, minorities continue to make up less than 10% of patients enrolled in clinical trials. This means that the survival data reported in trials may or may not accurately reflect outcomes in a racially heterogenous population such as the state of Louisiana. We retrospectively collected data from patients with advanced NSCLC treated with chemo-IO between January 2014 and January 2020 through our healthcare system Ochsner Health. Primary objectives were overall survival (OS) and progression free survival (PFS). Progression was defined per RECIST v1.1. Kaplan-Meier survival analysis was utilized to estimate PFS and OS. Survival curves were compared between the race strata using the log-rank test. We identified 264 patients with stage IV NSCLC who received chemo-IO. Median age was 65. 70% were white and 27% were black. 77% had adenocarcinoma and 20% had squamous cell carcinoma. 20% had brain metastases at diagnosis. 35%, 28% and 22% had a tumor proportion score of <1%, 1-49% and >50%, respectively. Probability of PFS at 12 and at 24 months was 0.61 (0.54-0.67) and 0.40 (0.32-0.48) respectively. Median PFS was 15.3 (13.2-18.9) months. Probability of OS at 12 and at 24 months was 0.61 (0.55-0.67) and 0.37 (0.29-0.44) with a median OS of 16.8 months (14.7-20.2). Median PFS among black and white patients was 21.9 (12.3-not estimable (NE)) and 15 (12.4-17.5) months, respectively (p= 0.135). Median OS among black and white patients was 20.2 (13.4-NE) and 16.2 (12.2-19.9) months, respectively (p= 0.114). Only 45 patients (17%) were able to receive 2nd line therapy. PFS and OS data for patients with stage IV NSCLC treated with chemo-IO reported in this study were not widely different from that data reported in prospective clinical trials. In the real world, delta between PFS and OS was much closer than in the clinical trials for stage IV NSCLC, with minority of patients going on to second line. Both PFS and OS were numerically superior in black patients compared to white patients, although the difference was not statistically significant. Further prospective studies with increased minority enrollment should be conducted to further evaluate any potential racial differences for patients with NSCLC on a larger scale.

P-125: An interim analysis of the Turkish Myeloma Registry among patients who have received up to two lines of therapy

<h3>Background</h3> To investigate the demographics and treatment details of the myeloma patients who were diagnosed and followed up in Turkey and received up to two lines of therapy. <h3>Methods</h3> Patients who were recorded on the database of Turkish Myeloma Registry project were included in this study if they had only received one or two lines of therapy. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. <h3>Results</h3> A total of 532 patients were included in the study 44% of the patients were female. Median age at the time of diagnosis was 63 (30-106). 47.7% of the patients were diagnosed with IgG myeloma. According to the ISS risk stratification, 20.4% of patients had ISS 1, 34.7% of patients had ISS 2 and remaining 44.9% had ISS 3 disease. Defining high risk disease as harboring one or more of these following cytogenetic abnormalities; del 17p, t(4;14), t(14;16) or t(14;20); 7.1% of the patients were classified as having a high risk disease. Most commonly used frontline therapy approach was bortezomib cyclophosphamide dexamethasone (VCD) (76.5%) and followed by bortezomib dexamethasone (VD) (8.8%), VRd (7.1%). Overall response rates (a better response than stable disease) were 87.6% in VCD induced patients; 63.3% in VD induced patients and 92% in VRd induced patients. The PFS obtained by these frontline approaches was 17.8 months in patients who were able to proceed with high dose chemotherapy with ASCT support and 8.4 in patients who were not able to (p<0.01), with an overall PFS of 15.3 months. With regard to the induction approach, PFS was 21.1 months for VRD, 15.3 months for VCD and 7.6 months for VD (p=0.08). Regarding maintenance, 23.6% of patients were maintained by lenalidomide alone, 62.7% of patients were maintained by a combination of lenalidomide and dexamethasone or bortezomib alone (2.7%). PFS after the first line of the treatment was 22.2 months in maintained patients and 12.2 in un-maintained patients (HR: 0.532, p=0.001, CI95% 0.359-0.790). Regarding the second line therapy Rd was the leading option (34.8%) and VRd (17.8%), Carfilzomib based (16.3%), VCD (8.1%) were the followings. <h3>Conclusion</h3> As the main concern of this study was to document the demographic features and clinical parameters of a Turkish Myeloma population and to give an idea about the treatment patterns and outcomes in frontline setting and first relapse an overall survival was not calculated. Progression free survival obtained after frontline therapy was relatively shorter than the ones which were presented by other real-world registries. Outcomes of second line therapy will be presented as follow up after 2nd line therapy exceeds a certain threshold. We hope, the results obtained from this study can have a role in the approval and reimbursement of the current standard of care options.

Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice.

We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6weeks could be a predictor of disease progression.

Retrospective analysis of chronic myeloid leukemia patients treated in the Department of Internal Medicine and Oncology, Semmelweis University, between 2003 and 2019

As a result of advances in diagnostic techniques and the introduction of tyrosine kinase inhibitors, the prognosis of chronic myeloid leukemia has improved over the last decades. Most of our knowledge about chronic myeloid leukemia results from clinical trials, therefore data derived from non-selected patient population is substantial. Data of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors at the Department of Internal Medicine and Oncology, Semmelweis University, between 2003 and 2019 were analysed retrospectively. 88 patients received treatment, 73 patients were on therapy at the time of the analysis. Overall survival at 5 years was 86%, progression-free survival at 5 years was 70%. 9 patients died, 2 of them due to progressive disease. 38 patients needed 2nd line therapy, the main reason of treatment change was failure of therapy. Subsequent treatment modifications were conducted mostly because of intolerance. More than half of the patients on 1st line treatment reached major molecular response and 85% of the patients on treatment at the end of the analysis are in major molecular response. Based on our data, survival and therapeutic response of patients in our center are similar to the international results. This analysis provides real-world data about treatment results of chronic myeloid leukemia in the tyrosine kinase inhibitor era. Orv Hetil. 2021; 162(32): 1297-1302.

Abstract 376: Prognostic significance of Glasgow prognostic score in NSCLC patients treated with immunotherapy after platinum-based cytotoxic chemotherapy

Abstract Introduction: The Glasgow prognostic score (GPS) reflects the host systemic inflammatory response and is validated prognostic factor in lung cancer. However, little is known about the prognostic role in non-small cell lung cancer (NSCLC) patients treated with immunotherapy after platinum-based cytotoxic chemotherapy. Patient and Methods: This study used a lung cancer cohort of the Catholic Medical Center of Korea between January 2018 and June 2020. We included the patients who were diagnosed with unresectable advanced stage NSCLC or recurrent disease after pulmonary resection and had received at least one regimen of platinum-based chemotherapy before being administered immunotherapy. The patients with NSCLC treated with anti-PD1 or anti-PD-L1 (pembrolizumab, nivolumab, or atezolizumab) and assessed the prognostic value of the GPS. The GPS was calculated using C-reactive protein and albumin concentrations within 1 week before starting anti-PD1 or anti-PD-L1 treatment. Results: A total of 78 patients with NSCLC treated with immunotherapy as 2nd or 3rd line therapy after platinum-based chemotherapy. Kaplan-Meier analyses revealed that higher GPS was significant predictors of shorter progression free survival (PFS) (Log rank &amp;lt; 0.001) and overall survival (OS) (Log rank &amp;lt; 0.001). In cox-regression multivariate analysis, the hazard ratios for disease progression were 2.146 (95% CI: 0.814-5.656; P = 0.123) for a GPS of 1 and 9.73 (95% CI: 2.931-32.298, P &amp;lt; 0.001) for a GPS of 2 relative to a GPS of 0. Older age (P = 0.033), lower PD-L1 expression (P = 0.036) and higher GPS (P = 0.007) were independently associated with shorter OS. Conclusion: Higher GPS were identified as one of poor prognostic factor for OS and PFS in NSCLC patients received immunotherapy as 2nd or 3rd line therapy after platinum-based chemotherapy. Citation Format: Hye Seon Kang, In Kyoung Kim, Jin Woo Kim. Prognostic significance of Glasgow prognostic score in NSCLC patients treated with immunotherapy after platinum-based cytotoxic chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 376.

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV.

BackgroundChemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI.MethodsRetrospective data were collected during routine care from German thoracic oncology centers. Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint.ResultsSeventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis.ConclusionsD+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS and will require further investigations.

Convulsive Status Epilepticus in a Cohort of Patients from a Peruvian Academic Hospital.

Background and PurposeStatus epilepticus is a neurologic emergency whose epidemiology, etiology and management are scarcely known in developing countries. Our objective was to describe the demographic and clinical features as well as the management of generalized convulsive status epilepticus (GCSE) in adult patients admitted to the emergency department of an academic hospital in Peru, between March 2019 and March 2020.MethodsObservational study of a prospective cohort in which patients were assessed by the emergency and neurology department on the first day of hospitalization, at discharge and at 30 days post-discharge in a follow-up visit. Relevant demographics and clinical data were collected. After being encoded and sorted, univariate statistical analysis was carried out.ResultsOf the sample of 59 patients, 62.7% were males, 57.6% were unemployed, 89.8% did not finish high school, and 55.9% had intermittent GCSE with no seizure at arrival. The total calculated median times were: 60 minutes from GCSE onset to hospital arrival, 110 minutes from GCSE onset to 1st line therapy, and 7 minutes from hospital arrival to 1st line therapy. The most frequently used antiepileptic drugs were one dose of benzodiazepine (41.7%), phenytoin (76.9%), and additional doses of benzodiazepines (60%) for 1st, 2nd, and 3rd line therapies, respectively. The most frequent etiologies were antiepileptic drug suspension (27.1%), undetermined (25.4%) and acute stroke (11.8%). 62.71% had 0–2 modified Rankin score at discharge.ConclusionsIn this cohort of patients, GCSE was mainly intermittent. Management times differed from the guidelines’ recommendations.

Treatment Patterns and Survival Outcomes in Latin American Patients with Newly Diagnosed Multiple Myeloma: A Retrospective Medical Chart Review Study, 2008-2016

Background: Recent advances in multiple myeloma (MM) treatment have led to overall improvement in patient outcomes around the world, although the incorporation of novel therapies is generally slow in Latin American countries. Currently, there is limited real-world evidence on available therapies and associated patient outcomes in this region.Objective: To evaluate the treatment landscape by examining up to 3 lines of therapy (LOTs) in Latin American patients with MM diagnosis and the impact of therapies on outcomes of progression-free survival (PFS) and overall survival (OS).Methods: Medical chart review was performed for patients with newly diagnosed MM at 30 participating clinical sites in 7 Latin American countries: Argentina, Brazil, Chile, Colombia, Mexico, Panama and Guatemala. All patients were followed from initiation of 1st LOT to the earliest of end of follow-up or death date (OS). PFS in each LOT was determined from initiation of each LOT until the earliest of end of follow-up, relapse date or death date. A multivariable Cox proportional hazard regression model was used to assess the association of therapy choice in 1st and 2nd LOTs with risk for disease progression or death, comparing patients with bortezomib (V)-based therapy against patients with other therapies. Patients receiving stem cell transplant were excluded from the analysis.Results: We identified1104 MM patients at initiation of 1st LOT with median age at diagnosis of 61 years. Median follow-up was 27 months; 48% patients had a history of cardio-related disease and 12% had a history of renal impairment. During the follow-up, 504 (46%) patients subsequently received a 2nd LOT, and 133 (12%) patients received additional 3rd LOT.Across all 1st, 2nd and 3rd LOTs, the 3 most commonly used regimens were thalidomide (T)-based regimen (excluding bortezomib), V-based regimen (excluding immunomodulators), and chemotherapy alone, accounting for 94%, 84% and 74% of 1st, 2nd and 3rd LOTs, respectively. T-based therapy was predominantly used in the 1st LOT and less often in subsequent LOTs, whereas use of V-based regimen and chemotherapy remained constant across the 3 LOTs (Table 1). Only a small proportion of patients were retreated by the same therapy, with 92 (18%) T-based patients, 28 (6%) V-based patients and 14 (3%) chemotherapy patients in both 1st and 2nd LOTs.With a median PFS time of 19 months in the 1st LOT, landmark PFS at year 1, 2, and 3 was 62%, 31% and 16%, respectively. Patients with T-based or chemo-therapy in their 1st LOT had ≥41% increased risk for relapse during 1st LOT than those with V-based therapy (p<0.01, Table 2a). In 2nd LOT, the median PFS was 10 months; landmark PFS at year 1, 2 and 3 was 36%, 13% and 5%, respectively. No statistical differences in landmark PFS for 2nd LOT were observed among the 3 treatments (p≥0.09, Table 2b).Following initiation of 1st LOT, 357 (32%) patients died. In 1st LOT, OS rate at year 1, 2, and 3 was 84%, 55% and 35%. There was no difference in mortality risk between patients using T- and V-based therapy (p=0.95), although chemotherapy patients had 43% increased mortality relative to V-based patients (p<0.05, Table 2c). Similar association was also observed in 2nd LOT (Table 2d), with median OS time of 17 months.When individual countries were assessed in 1st LOT, Brazilian patients, relative to those in other 6 countries, had shorter median PFS (10 months) and median OS time (23 months). Common treatments in Brazil across the 3 LOTs were similar to those in other countries. Also, a somewhat stronger association between treatment choice and outcomes of PFS and OS was seen in Brazil (Table 3).Conclusion: This study shows the latest findings of treatment patterns and associated outcomes in MM patients from 7 Latin American countries. The continued high prevalence of T-based therapy use after 2008 in these patients suggests that several Latin American countries have limited treatment options. Following initiation of 1st LOT, ~70% patients experienced 1st disease progression within 2 years and >40% of patients died from the disease. Brazilian patients appear to have worse PFS and OS in 1st LOT than patients from other countries, likely attributable to treatment choice. Better management of care for MM, such as increased use of novel agents and new treatment sequence are needed to prolong PFS and OS in these patients. [Display omitted] DisclosuresHungria:Celgene, Roche, Takeda, Janssen, Amgen: Honoraria. Miguel:Janssen: Speakers Bureau. Silvana Cugliari:Roche, Raffo, Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Santos:Janssen: Employment. Santos:Janssen: Employment. Machnicki:Janssen: Employment. Lin:Janssen: Employment. Chen:Janssen: Employment. Barreyro:Janssen: Employment.

Sequencing Therapy in Chronic Lymphocytic Leukemia (CLL): Treatment Patterns and Associated Outcomes in Community Practice for Patients with Relapsed/Refractory CLL in the United States

Background: CLL is the most common type of leukemia in adults in the US. Traditionally, chemotherapy (CT) and chemoimmunotherapy (CIT) have been the treatment mainstay, with new oral-targeted options recently becoming available. CLL patients (pts) who relapse and/or are refractory to their initial treatment have poorer outcomes compared with pts who are treatment naive, especially if they harbor high-risk genetic features (eg, 17p deletion [del(17p)]). As oral-targeted therapies became available in the US for pts with CLL, including those positive for del(17p), treatment patterns have changed. However, questions about how to sequence new therapies and traditional CIT/immunotherapy (IT) remain.Aims: This study used an electronic health record database to characterize treatment sequencing and associated outcomes in relapsed/refractory (R/R) CLL pts. The association between treatment choices and outcomes stratified by del(17p) status and previous line of therapy (LoT) was also explored.Methods: This was a retrospective observational study in CLL utilizing a large, longitudinal, demographically and geographically diverse database of US cancer pts (Flatiron Health 06/2017). An analytic cohort of pts treated mostly at community practice sites who initiated a LoT after Jan 2014 was developed. Time to next LoT or death (TTNLD), defined as the start date of a LoT to the start date of next LoT or death or the date of data cut, whichever comes first, was analyzed by Kaplan-Meier method. A Cox proportional hazard model was used for unadjusted and adjusted analyses including hazard ratios (HR) estimation.Results: The analytic cohorts included 1,457 and 613 pts who initiated 2nd and 3rd LoT with either B-cell receptor or B-cell lymphoma 2 (BCR/BCL2) inhibitor or CT/CIT/IT after Jan 2014. Average age at CLL diagnosis was 64.8 years (64.0 years); 61.6% (60.7%) of pts were male; and 72.2% (71.8%) were Caucasian (2nd LoT, 3rd LoT, respectively). A subcohort included 374 pts who received either BCR/BCL2 or CT/CIT/IT as 2nd LoT following initial CT/CIT/IT. Among these 374 pts, 161 (43.0%) were treated with a BCR/BCL2 inhibitor; 213 (57.0%) were treated with CT/CIT/IT for the 2nd LoT. The rate of del(17p)-specific testing before initiation of 2nd LoT was 67.1%, and 68.4% before the initiation of 3rd LoT.Median TTNLD in del(17p)-negative pts who initiated 2nd LoT with a BCR/BCL2 inhibitor was not reached (proportion of pts who experienced TTNLD at 06/2017 was less than 50%; Figure 1) vs 21.5 months in pts who initiated 2nd LoT with CT/CIT/IT; similarly, for del(17p)-positive pts: 28.3 months with BCR/BCL2 inhibitors vs 9.8 months for CT/CIT/IT. Pts treated with a BCR/BCL2 inhibitor had a lower risk of advancing to subsequent LoT than pts treated with CT/CIT/IT (HR 0.56; 95% CI: 0.47-0.67 [Figure 1, Table]).Median TTNLD in del(17p)-negative pts who initiated 3rd LoT with a BCR/BCL2 inhibitor was 31.6 vs 12.2 months in pts who initiated 3rd LoT with CT/CIT/IT; similarly, for del(17p)-positive pts: 12.6 months with BCR/BCL2 inhibitors vs 5.5 months for CT/CIT/IT. The HR for advancing from 3rd LoT to subsequent LoT was 0.46 (95% CI: 0.36-0.58) for pts treated with a BCR/BCL2 inhibitor compared with CT/CIT/IT (Figure 2, Table).Pts who were treated with 2nd-line BCR/BCL2 inhibitor following CT/CIT/IT had a median TTNLD that was not reached, significantly longer than the median TTNLD in pts who had CT/CIT/IT after initial CT/CIT/IT (median 26.6 months; HR 0.52; 95% CI: 0.35-0.78).Conclusion: In this real-world analysis of treatment pattern of CLL pts, regardless of del(17p) status or LoT (2nd or 3rd), R/R CLL pts receiving an oral-targeted therapy had a longer TTNLD compared with pts receiving CT/CIT/IT. In particular, pts receiving a BCR/BCL2 inhibitor as subsequent LoT to initial treatment with CT/CIT/IT had a longer TTNLD than pts receiving CT/CIT/IT following CT/CIT/IT. [Display omitted] DisclosuresKapustyan:AbbVie Inc.: Employment, Equity Ownership. Keim:AbbVie Inc.: Employment, Equity Ownership, Other: I am an employee of AbbVie, Inc and may own AbbVie and/or Abbott stock. Meissner:AbbVie Inc.: Employment, Equity Ownership, Other: I am an employee of AbbVie, Inc and may own AbbVie and/or Abbott stock. Nielsen:AbbVie Inc.: Employment, Equity Ownership. Zhang:AbbVie Inc.: Employment, Equity Ownership. Jiang:AbbVie Inc.: Employment, Equity Ownership.

Cost Offsets in the Treatment Journeys of Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

BackgroundMultiple new regimens combining different mechanisms of action and routes of administration are available for the treatment of RRMM. It is increasingly important to understand the differential costs of these regimens, including patient and caregiver burden of treatment and associated indirect costs. The objectives of this study were to determine the costs associated with treating RRMM with 2nd-line therapy and cost offsets associated with frequently used regimens in this setting.MethodsA 12-month (mo) treatment journey for RRMM was developed to reflect real-world clinical practice based on current treatment guidelines and input from hematologists/oncologists. Regimens used as 2nd- or 3rd-line therapy were included, incorporating thalidomide (T), lenalidomide (R), pomalidomide (Pom), bortezomib (V), carfilzomib (K), ixazomib (I), elotuzumab (E), daratumumab (D), panobinostat (Pa), cyclophosphamide (C), melphalan-prednisone (MP), and dexamethasone (d/dex). Specific regimens were: Rd, Vd, VRd, VCd, Pom-dex, Kd, MPT, VMP, KRd, IRd, ERd, DVd, and PaVd. Data on DRd were not available when the model was developed. A cost model was constructed to determine costs associated with 2nd-line treatment with these regimens, including direct (medical/laboratory [lab], drug, administration, pre-medication, prophylaxes, adverse event [AE]-related) and indirect (productivity loss, transportation, caregiving) costs incurred at the initiation of and during 2nd-line therapy, and for a subsequent line of therapy among patients who discontinued 2nd-line therapy due to disease progression or AEs.ResultsDrug cost represented the primary cost component of the total cost of 2nd-line therapy across all regimens; analyses excluding these costs highlight additional direct and indirect drivers of treatment journey costs. Total costs excluding drug costs (Fig 1) appeared highest with regimens with substantial rates of discontinuation due to AEs, such as MPT, and with triplet regimens in which one or more of the agents was administered by intravenous (IV) or subcutaneous (SC) infusion, such as DVd, KRd, PaVd, VRd, and ERd. Compared to other recently approved doublet or triplet regimens, excluding drug costs, IRd appeared less expensive than Kd, KRd, ERd, DVd, and PaVd, driven by lower administration costs, AE-related costs, and indirect costs. Direct medical costs, including medical visits, lab tests, administration costs, and costs for prophylaxes, were $140.97 for the all-oral regimens IRd, Rd, and Pom-dex (12-mo cost: $1,691.61). Direct medical costs were higher for V-containing regimens, such as Vd ($707.75; 12-mo cost: $8,493.01), VRd ($708.29; 12-mo cost: $8,499.50), and VCd ($561.72; 12-mo cost: $6,740.69), compared to all-oral regimens, driven by higher administration and lab test costs. Similarly, compared to all-oral regimens, direct medical costs were higher for regimens containing novel drugs requiring clinic administration, such as Kd ($1,009.65; 12-mo cost: $12,115.75), KRd ($1,010.19; 12-mo cost: $12,122.24), ERd ($795.00; 12-mo cost: $9,539.99), DVd ($1,122.63; 12-mo cost: $13,471.61), and PaVd ($707.75; 12-mo cost: $8,493.01). AE management costs were estimated on average (all regimens) to be $243.37 per 28-day cycle (12-mo cost: $2,920.42), and were lower with Vd ($103.58; 12-mo cost: $1242.91) and higher with Pom-dex ($395.58; 12-mo cost: $4,747.00) and PaVd ($306.02; 12-mo cost: $3,672.20). Indirect costs (Fig 2) were higher for regimens requiring more frequent or longer drug administration, such as DVd ($702.78; 12-mo cost: $8,433.33), Kd, and KRd ($511.26; 12-mo cost: $6,135.06), and lowest for all-oral regimens ($78.19; 12-mo cost: $938.30). Adjusted cost offsets will be reported for subgroups with high unmet need, including frail patients, patients with barriers to physician access, and patients with pre-existing cardiac disease or other comorbidities.ConclusionsExcluding drug acquisition costs, differences in total costs between regimens for RRMM were driven primarily by administration costs, AE-related costs, and indirect costs. The results of this study of costs accrued over 12 mos for specified regimens demonstrate the lower treatment burden (direct medical costs) and indirect costs associated with administering all-oral regimens compared to the specified regimens requiring frequent and/or lengthy IV or SC administration. [Display omitted] DisclosuresAilawadhi:Takeda: Consultancy, Honoraria; Pharmacyclics: Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. DerSarkissian:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding; Novartis Pharmaceuticals Corporation: Employment. Duh:Novartis Pharmaceuticals Corporation: Research Funding; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding. Lafeuille:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd: Research Funding; Janssen Scientific Affairs, LLC: Research Funding. Posner:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding. Ralston:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding. Zagadailov:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Ba-Mancini:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Rifkin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; McKesson Specialty Health: Employment; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

The Evolving Impact on Survival Outcomes in Multiple Myeloma with Greater Access to Novel Treatment Regimens: Experience in a Real-World Cohort

The Evolving Impact on Survival Outcomes in Multiple Myeloma with Greater Access to Novel Treatment Regimens: Experience in a Real-World Cohort

What's Next in CML - a Prospective Study Evaluating Sanger Sequencing and Next Generation Sequencing (NGS) for BCR-ABL1 Kinase Domain (KD) Mutation Screening

What's Next in CML - a Prospective Study Evaluating Sanger Sequencing and Next Generation Sequencing (NGS) for BCR-ABL1 Kinase Domain (KD) Mutation Screening

Multicenter Retrospective Study of Features and Outcomes of Patients with Intravascular DLBCL Treated at Academic Institutions within the United States

Multicenter Retrospective Study of Features and Outcomes of Patients with Intravascular DLBCL Treated at Academic Institutions within the United States

Sirolimus Is Effective in Refractory Immune Thrombocytopenia: Results of an Open-Label Prospective Multicenter Trial in China

Background: Immune thrombocytopenia (ITP) is an autoimmune disease mainly due to increased destruction of platelets and decreased platelet production. Prednisone 1 mg/kg/d for 2 to 4 weeks has been the standard first-line treatment for many years. Splenectomy, rituximab and cyclosporine were commonly used second-line therapies. About 20-30% ITP patients have no response to both first-line and second-line therapies or cannot maintain the response and are diagnosed with refractory ITP. There is limited evidence for the treatment of refractory ITP. The international guideline for management of ITP suggested combined therapies but about half of the patients still fail to respond. In addition, thrombopoietin-receptor agonists are not available in China. Therefore, we investigated in alternative therapeutic options for the management refractory ITP in China.Sirolimus (rapamycin) is an immunosuppressive compound that targets the mammalian target of rapamycin (mTOR) and has been shown to induce apoptosis of both normal and abnormal lymphocytes. Recently, it has been demonstrated that treatment with sirolimus could induce complete responses (CR) in patients with corticosteroid refractory autoimmune cytopenias, including four refractory ITP patients. Based on those studies, we initiated an open-label prospective multi-institutional clinical trial (ChiCTR-ONC-17012126) using sirolimus for patients with refractory ITP in Southwest China.Methods: Refractory ITP was defined as platelet count <50 X109/L without other complications that may cause thrombocytopenia and patient has failed prednisone therapy and at least one 2nd-line therapy (prednisone + cyclosporine / splenectomy / rituximab). Sirolimus was given at a dose of 2 mg per day orally (maximum initial dose of 4 mg/day) and target a trough level of 4-15 ng/ml in circulation. The anticipated length of treatment with sirolimus was 3 months, and then taped down 0.5mg per two weeks. Patients were followed up every week for 1 year. Platelet count was measured once a week. Complete response is defined as platelet count > 100×109/L and partial response (PR) is defined as platelet count > 100×109/L or increased more than two times. Side effects were evaluated during every visit.Results: Between 01/2016 and 06/2016, 73 patients were included in the trial and 66 patients completed the trial and follow-up. In 66 patients, the median age was 47 (16-68) years; 77.3% were female; 48.5% ITP patients treated with prednisone + cyclosporine, 30.3% treated with prednisone + rituximab, 13.6% treated with prednisone + splenectomy, and 7.65% treated with prednisone + two of the four second-line treatments. Fourty-six of 66 patients responded to the therapy (30 CR and 16 PR) within 3 months of sirolimus therapy. So the response rate and CR rate are 69.7% and 45.5% respectively. In patients with CR, the median duration of platelet recovery to 100×109/L was 4 weeks (Figure 1). Risk factor analysis involving age, sex, previous treatment and platelet count before sirolimus treatment were undertaken to identify whether any factor might have an effect on the outcome of sirolimus treatment. As a result, platelet count prior to treatment was the only factor that affects the efficacy of sirolimus. During sirolimus treatment and reduction, 6 patients developed oral ulcers, 8 patients with hypertriglyceridemia, 6 patients with diarrhea and 2 patients with interstitial pneumonia. All side effects were grade 1-2 according to CTCAE 4.0.Conclusion: In summary, in our current study, more than half of the patients with refractory ITP responded to sirolimus. While the response rate is promising, there is limited evidence of side effects and long-term follow-up. Despite of this, it may worthwhile further investigations for larger scale randomized clinical trials for the evaluation of sirolimus in refractory ITP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Navigating the Changing Multiple Myeloma (MM) Treatment Landscape: Real-World Data on Clinical Practice Patterns in 287 MM Patients Treated in and Outside German DSMM (Deutsche Studiengruppe Multiples Myelom) Study Group Trials

Introduction: Over the last decade MM diagnosis and therapy have greatly improved; notably due to an increasing number of “novel agents” (NA; e.g. PIs, IMiDs, mAbs, HDAC-, PD1/PD-L1-inhibitors). Anti-MM-therapy has gained complexity; orientation towards “state of the art” chemotherapy (CTx) protocols and international guidelines, as well as their continuous evaluation is highly important. According to the international literature, analyses of CTx management and particularly the use of novel substances have mainly been performed in the context of clinical trials (CT), therefore in a selected minority of patients (pts). In order to determine, whether guideline recommendations on MM therapy are thoroughly implemented in- and outside CT settings, we performed a real-world data analysis on clinical MM practice patterns. Substance use was analyzed in view of treatment lines and evaluated for “MM-pathway conformity”.Methods: We performed a detailed analysis of 287 myeloma pts treated at our University Medical Center, part of the DSMM study group in 2014/15. The pt cohort was defined using the hospital pharmacy and tumor documentation (TBD) databases. TBD analysis enabled the detailed acquisition of pt characteristics, such as age at initial diagnosis (ID), gender, Durie and Salmon (D&S) and International Staging System stage (ISS). Status of transplantation (Tx), comorbidity (via Revised Myeloma Comorbidity Index [R-MCI]), CT data, treatment line/cycle and the year of CTx application were collected using electronic medical records, TBD and CTx management tools. Basic data on therapy composition was collected for the years 2005 to 2017, separating two treatment periods for 1st, 2nd and 3rd-line therapy of 2005-2012 and 2013-2017. This cut-off was carefully chosen to discriminate best between NA- and non-NA-based regimens, and between first generation PI- (bortezomib (BOR) and IMiD-use (thalidomide (THAL), lenalidomide (LEN)) and second generation NA.Results: Pt characteristics were representative for tertiary centers with a median age of 63 years (27-89), 54% were 60-79 and 14% >80 years old. The male:female gender ratio was 58%:42% and ISS predominantly advanced (II/III:62%). Pts showed substantial comorbidities and were classified as fit, intermediate-fit and frail according to R-MCI in 33%, 56% and 11%, respectively. Of interest, 33% of pts could be enrolled in CTs and 88% received 1st line treatment at our center. 275 pts received 1st-line, 149 pts 2nd-line and 97 pts 3rd-line treatment (Fig.1). As expected, numbers of pts decreased with subsequent lines of treatment, albeit the median time to 2nd line therapy due to progression amounted to 2 years. As depicted in Fig.1, 1st line conventional CTx (cCTx) alone was rare and substantially declined over time from 12% 2005-2012 to 1% in 2013-2017. 200 pts (73%) were treated with BOR in 1st line, 63 of 106 reinduced pts received BOR in 2nd or 3rd line. IMiD 2nd and 3rd line treatment was also common within different regimens and the combination of 2 NA of both PI+IMiD increased over time (BOR+THAL, BOR+LEN). The use of second generation NA in 2nd and 3rd line treatment notably increased in 2013 to 2017 in line with their approval. Our analysis revealed that 44% of second generation NA protocols were administered outside CT settings, mainly due to tight inclusion and wide CT exclusion criteria. Maintenance was performed in 57% of pts, predominantly with LEN (60%) and within DSMM CT protocols.Conclusion: Our analyses demonstrate that NA combinations are used predominantly today, whereas the use of cCTx alone is substantially declining. While BOR plays an important role in induction, LEN was subsequently used for maintenance and in outpatient-regimens. BOR-reinduction as a validated treatment option is also reflecting the substantial amount of BOR-based protocols worldwide. A significant percentage of second generation NA are administered outside CT settings, representing the fast and effective implementation of guideline recommendations into the real-world clinical practice at our and other MM centers. Currently, we are assessing the percentage of pts discussed in our weekly MM tumorboard, the evidence level of therapeutic interventions, PFS and OS. Results will be shown at the meeting, including the comparison of our data with others in a detailed review of the literature. [Display omitted] DisclosuresEngelhardt:German Cancer Aid (#11424): Other: Educational Grant; Janssen Cilag GmbH: Other: Educational Grant; Celgene GmbH: Other: Educational Grant; Amgen GmbH: Other: Educational Grant.

Early Relapse Post Autologous Transplantation Is Associated with Very Poor Survival and Identifies an Ultra High Risk Group of Myeloma Patients

Treatment with high dose melphalan (HDM) and autologous stem cell transplantation (ASCT) improves progression free survival (PFS) and overall survival (OS) of myeloma patients and is a standard therapy for eligible patients. Furthermore, the use of maintenance therapy after ASCT is beneficial. However, a subset of patients relapses early after HDM, and there is a paucity of data about their outcomes and characteristics, especially regarding their identification at diagnosis or early in the course of the disease. The aim of the current study was to describe the characteristics, the management and outcomes of patients relapsing within 12 months from HDM.The study included 297 consecutive patients treated in the Department of Clinical Therapeutics, Athens, Greece, which received HDM-ASCT as part of first line therapy from 1995 until June 2016. Median age was 55 years (range 22-67); 38% were ISS-1, 31% ISS-2 and 30% ISS-3. Induction was bortezomib-based in 47%, thalidomide-based in 13%, lenalidomide-based in 6%, high dose dexamethasone-based in 25% and contained both bortezomib and an IMiD in 9%. After ASCT, 35% received consolidation and 30% maintenance.Median follow up for all patients is 5 years, 183 (62%) have relapsed, the median PFS post HDM was 36 months and 43 (13.5%) patients have progressed within <12 months post HDM. In univariate analysis, the baseline LDH ≥250 IU/L (37% vs 15%, p<0.001), eGFR <30 ml/min (22% vs 12%, p=0.055), hypercalcemia (26% vs 16%, p=0.069) and high-risk cytogenetics (available in 138 patients) (39% vs 23%, p=0.084) were associated with early relapse. Response to induction therapy was not predictive of early relapse but less than sCR/CR post HDM (day 100) was associated with early progression (p=0.1). The use of consolidation therapy post HDM was associated with lower rates of early relapses (4% vs 14% for maintenance and 26% for no post-HDM therapy, p<0.001). In multivariate analysis, LDH ≥250 IU/L (HR: 3.4, p=0.01) and hypercalcemia (HR: 3, p=0.006) at diagnosis increased while the use of consolidation reduced the risk of early relapse (HR: 0.23, p=0.012). Due to the limited number of patients with cytogenetics this parameter was not included in the multivariate model.Baseline characteristics that were associated with PFS post HDM included high-risk cytogenetics (HR: 2.1, p=0.003), ISS-3 (HR: 1.4, p=0.03), hemoglobin <10 g/dl (HR: 1.6, p=0.001), hypercalcemia (HR: 1.6, p=0.014) and achievement of sCR/CR after HDM (HR: 0.8 vs VGPR, p=0.18 and HR: 0.67 vs PR, p=0.06). The use of maintenance therapy (HR: 0.54, p=0.01) was also associated with better PFS. In multivariate analysis, the use of maintenance therapy (HR: 0.58, p=0.032) and sCR/CR post HDM (HR: 0.64 vs PR, p=0.06 and HR: 0.9 vs VGPR, p=0.17) were independently associated with PFS. In further analysis, PFS to 2nd line therapy was 14 months for all patients, but only 5 months for those with an early relapse vs 19 months for the other patients (P<0.001). Median PFS2 was 15.5 months for patients with a relapse <12 months post HDM vs 57% at 5 years for the other patients (p<0.001).The 5-years OS is 67%, but, median post HDM OS was 18 months for those with an early relapse vs 71% at 5 years for those with post HDM PFS ≥ 12 months (p<0.001; Figure). In univariate analysis prognostic factors for OS after HDM included high risk cytogenetics (HR: 3, p<0.001), ISS-3 (HR: 2.2, p<0.001), hypercalcemia (HR: 2.8, p<0.001), anemia (HR:1.9, p=0.001), LDH ≥250 IU/L (HR: 1.7, p=0.054) and sCR/CR after HDM (HR: 0.7, p=0.082), use of maintenance (HR: 0.5, p=0.014) or consolidation (HR: 0.61, p=0.017) after HDM. In multivariate analysis PFS post ASCT <12 months (HR: 14, p<0.001) was the most important prognostic factor; other factors included post-HDM sCR/CR (HR: 0.48 vs PR, p=0.021 and HR: 0.54 vs VGPR, p=0.054), hypercalcemia at diagnosis (HR:2.1, p=0.005) but not maintenance (p=0.1) or consolidation therapy (p=0.54) post ASCT.In conclusion, 13% of patients with newly diagnosed MM that receive HDM at first remission relapse within 12 months after ASCT and they have very poor outcomes. These patients should be considered as an ultra high-risk group that urgently needs more effective therapies and innovative approaches through targeted clinical trials. The use of consolidation in patients at high risk for early relapse, such as those with high LDH and hypercalcemia at diagnosis, may reduce early relapses, and maintenance may prolong PFS. [Display omitted] DisclosuresKastritis:Janssen: Honoraria, Research Funding; Gebesis/Celgene: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria. Terpos:Abbvie: Honoraria; BMS: Honoraria; Amgen: Honoraria, Other: SC member, Research Funding; Janssen: Honoraria, Research Funding; Genesis/Celgene: Honoraria, Other: DMC member, Research Funding; Takeda: Honoraria, Other: SC member; GSK: Honoraria. Dimopoulos:Novartis: Consultancy, Honoraria; Genesis Pharma: Research Funding; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology.

324-OR: Global Use of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Type 2 Diabetes: Results from DISCOVER

Background: Despite strong evidence of benefit, uptake of newer glucose-lowering medications that reduce cardiovascular risk has been poor. We examined global trends and predictors of use of SGLT2i and GLP-1 RA in patients with T2D. Methods: DISCOVER is a global, prospective, observational study of patients with T2D enrolled from 2014-16 at initiation of 2nd-line glucose-lowering therapy and followed for 3 years. We used hierarchical logistic regression to examine factors associated with use of either SGLT2i or GLP-1 RA at 3 years. Results: Among 14,576 patients from 37 countries, 1579 (10.8%) were started on an SGLT2i (8.7%) or GLP-1 RA (2.2%) at enrollment as 2nd-line therapy. This increased to 16.1% at end of follow-up (13.5% SGLT2i, 3.3% GLP-1 RA). Median use across the 37 countries at 3 years was 19.4% (IQR 8.7-30.6%; range 0-62.7%). Younger age, male sex, higher BMI, and coronary disease were associated with higher use of SGLT2i/GLP-1 RA while peripheral artery disease and kidney disease were associated with lower use. Conclusions: Global use of glucose-lowering medications with cardiovascular benefits has increased over time (particularly SGLT2i) but remains suboptimal, particularly in sub-groups most likely to benefit. Substantial country-level variability exists independent of patient factors, suggesting structural barriers may limit more widespread use of these medications. Disclosure S. V. Arnold: None. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Berlin-Chemie AG, Lilly Diabetes, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novo Nordisk, Roche Pharma, Sanofi-Aventis. M. N. Kosiborod: Consultant; Self; Amgen Inc., Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk, Sanofi, Vifor Pharma Management Ltd., Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. F. Tang: Other Relationship; Self; AstraZeneca. A. Cooper: Employee; Self; AstraZeneca. H. Chen: None. M. B. Gomes: None. W. Rathmann: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk. I. Shimomura: Advisory Panel; Self; AstraZeneca K. K., Daiichi Sankyo, Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., Consultant; Self; MSD K. K., Novo Nordisk Pharma Ltd., Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Novartis Pharma K. K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca K. K., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho, Taiho Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. J. Vora: Advisory Panel; Self; Bayer Inc., Other Relationship; Self; AstraZeneca. H. Watada: Research Support; Self; Abbott Japan Co., Ltd., Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Kyowa Kirin Co., Ltd., Lilly Diabetes, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation. Funding AstraZeneca

PCN13 Quality-of-Life (QOL) Results from the Phase 3 Rainbow-ASIA Study of Ramucirumab PLUS paclitaxel (RAM/PTX) Versus Placebo PLUS paclitaxel (PBO/PTX) in Patients with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (AGC)

In RAINBOW-Asia study (NCT02898077), a bridging study of RAINBOW, RAM/PTX compared with PBO/PTX demonstrated consistent efficacy benefit [PFS: 4.14 vs. 3.15 months, Hazard ratio (HR)=0.765, p=0.0184; OS: 8.71 vs. 7.92 months, HR=0.963] and safety profile with RAINBOW study in a predominantly Chinese population with AGC as 2nd-line therapy. Here we will present results of QoL of the study. Patients with AGC who previously received fluoropyrimidine- and platinum-based therapy were randomized at 2:1 ratio to receive RAM/PTX or PBO/PTX. Patients completed the EORTC QLQ-C30 (v3) at baseline, first day of each 4-week cycle and at discontinuation. Scores were classified as improved or deteriorated if changed by ≥10 points (on 100-point scale) relative to baseline, otherwise classified as stable. Time to deterioration in QoL parameters was defined as duration from randomization to first deterioration. HRs and 95% confidence interval (CI) were estimated using stratified Cox proportional hazard model. Of 440 patients randomized, 272/294 (92.5%) of RAM/PTX and 133/146 (91.1%) of PBO/PTX patients provided both baseline and post-baseline data. Percentage of compliance was high (>95% in most cycles) and similar between arms. For all QoL parameters, the proportion of patients reporting improved or stable scores was generally similar between arms at all on-therapy assessment times. For time to deterioration, HRs for 11 of the 15 QoL scales had 95% CI that included 1, indicating no significant difference in those scales between arms. HRs for 4 symptom scales including dyspnea, insomnia, appetite loss, and diarrhea did not favor RAM/PTX arm, which was consistent with slightly higher incidence of all-grade (primarily low-grade) treatment-emergent adverse events in this arm. Similar proportion of patients reported improved or stable QoL scores between arms and no evidence of detriment to QoL in majority of scales by treatment with RAM/PTX as 2nd-line therapy in this population.

P453 The use of immunosuppresants is associated with high treatment persistence rates for infliximab and adalimumab as first or second line anti-TNF therapy in patients with inflammatory bowel disease

Abstract Background The aim of this study was to investigate the factors associated with treatment persistence for infliximab and adalimumab, as 1st or 2nd line anti-TNF therapy, in patients with inflammatory bowel disease (IBD). Methods A retrospective study of patients with IBD from the registry of our department who received infliximab (IFX) or adalimumab (ADA), during the period of 2002–2019 was performed. The persistence rate of IFX and ADA at 1 and 3 years from treatment initiation as 1st and 2nd line anti-TNF therapy respectively was calculated. In addition, possible related factors were analyzed. Results We included 185 patients with IBD, naive to biologics, who initiated with anti-TNF treatment [105 men (57%), mean age (± SD) 44.5 ± 14.7 years, Crohn’s disease 144 (78%), median disease duration (IQR) 13 (7–20) years, 120 (65%) under IFX, 100 (55%) in combination with immunosuppressive therapy for at least 6 months]. In 59 patients [Crohn’s disease 47 (80%)] IFX or ADA was used as 2nd line anti-TNF therapy. The duration of administration and persistence rate of IFX and ADA as 1st and 2nd line treatment are shown in Table 1. In univariate analysis statistically significant associations between the persistence rates of anti-TNF therapy as first-line therapy, with the use of immunosuppressants (P = 0.04) and treatment intensification (P = 0.01) in both 1st and 3rd year (P = 0.01 and 0.04 respectively) were found. No other significant association between demographic, disease type and clinical parameters and treatment persistence was found. Regarding the 2nd line anti-TNF treatment, persistence of therapy in the 1st year was associated with treatment intensification (P = 0.02) and in the 3rd year of administration with the combination with immunosuppressants (P = 0.05). In multivariate analysis only the use of immunosuppresants remained statistically significant associated both in 1st and 3rd year of treatment in 1st line therapy (P=0.05 and P=0.003 respectively). This was also the case in 2nd line therapy but only in the 3rd year of treatment (P=0.05). Conclusion The persistence rates of IFX and ADA used both as a 1st and 2nd line therapy in IBD patients are significantly associated with the combined use of immunosuppressants.

Treatment patterns and outcomes among patients with microsatellite stable (MSS) advanced endometrial cancer in the United States: Endometrial Cancer Health Outcomes (ECHO) retrospective chart review Study.

5581 Background: Traditional platinum-based systemic chemotherapy continue to be the SOC for aEC in the first line. Phase 2 clinical trials of chemotherapy (GOG 129 series) and some targeted therapies (229 series) for second line advanced endometrial cancer (aEC) have proved disappointing. Recently the treatment landscape for aEC patients has significantly changed with newer targeted therapies focusing on the microsatellite instability (MSI) status of endometrial tumors. The objective of the ECHO study was to describe real-world treatment patterns and outcomes in non-MSI-high or DNA mismatch repair proficient (pMMR) aEC patients in clinical practice in the United States (US) prior to 2019. Methods: The ECHO study is a multicenter, retrospective chart review study in women diagnosed with aEC in the US. Data were obtained from medical records of adult women (≥18 years) diagnosed with advanced or inoperable aEC (stages III or IV) with known MSI status, who had received at least one prior systemic therapy and progressed between July 1, 2016 – June 30, 2019. De-identified patient data extracted by treating oncologists included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed to estimate real-world progression-free survival (rwPFS) and overall survival (OS). Results: A total of 124 non-MSI-high or pMMR aEC patients who had progression following first line therapy were included in this interim analysis. Average age was 63 years, 62.9% White/Caucasian, 16.9% Hispanic/Latino, and 86% had ECOG ≤1. Metastases were observed in 70% of patients at diagnosis, with the most common metastatic sites being lung (47.6%), liver (32.3%), and distant lymph nodes (29%). As 2nd line therapy, 69% of patients received mono or combination chemotherapy (primarily with doxorubicin), 13% hormonal therapy, and 18% targeted therapy ± chemotherapy. Median duration of 2nd line therapy was 4 months. The majority (86.3%) discontinued 2nd line therapy, with disease progression the most common reason (66.4%). A quarter (26.6%) of patients initiated an additional line of therapy. Median rwPFS from initiation of 2nd line therapy was 5 months (95% confidence interval [CI]: 4-9). Median OS from initiation of 2nd line therapy was 12 months (95%CI: 9-18). Estimated OS rates from initiation of 2nd line therapy at 6, 12, and 24 months were 66%, 47%, and 30%, respectively. Conclusions: In this retrospective, chart review study, patients with non-MSI-high/pMMR aEC in the US who failed at least one systemic therapy had poor prognosis on subsequent therapies. There continues to be a significant unmet need in this group of women. Novel therapies are needed that delay progression and/or improve overall survival and further research is indicated to explore this.