Treatment-emergent Adverse Events Of Interest Research Articles

Resolution of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with Defibrotide Following HCT in Adult and Pediatric Patients: Pooled Analysis of Defifrance and EBMT PASS Registries

Introduction Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT). Defibrotide is approved for the treatment of severe VOD/SOS post-HCT in patients aged >1 month in the European Union and for VOD/SOS with renal or pulmonary dysfunction post-HCT in the United States. Outcomes from two real-world observational studies were pooled for analysis of treatment duration and time to resolution of VOD/SOS in patients given defibrotide for the treatment of severe or nonsevere VOD/SOS post-HCT. Methods DEFIFrance was an observational study that collected retrospective and prospective data on patients receiving defibrotide at 53 French transplant centers from July 2014 to March 2020. VOD/SOS severity was categorized retrospectively/prospectively using adult European Group for Blood and Marrow Transplantation (EBMT) criteria in patients aged ≥18 years, and in patients aged <18 years using pediatric EBMT criteria. EBMT PASS was a multinational, prospective, observational study that enrolled defibrotide-treated patients from April 2015 to July 2018. VOD/SOS severity was graded based on investigators' clinical expertise. For this pooled analysis, mild/moderate and severe/very severe cases in DEFIFrance were combined with nonsevere and severe cases in EBMT PASS, respectively. Investigators in both registries diagnosed VOD/SOS using classical/standard criteria. Results Overall, 414 defibrotide-treated patients with VOD/SOS post-HCT were included (336 from DEFIFrance and 78 from EBMT PASS). The median (interquartile range [IQR]) time from HCT to VOD/SOS diagnosis was 13 (IQR: 8, 21) and 14 (IQR: 8, 22) days in patients with severe and nonsevere VOD/SOS, respectively. Overall, 299/410 patients (73%) had resolution of VOD/SOS. Disease severity data was missing from 4 patients. Among 275 adult patients, VOD/SOS resolution was achieved in 44/60 (73.3%) with nonsevere and 128/215 (59.5%) with severe VOD/SOS. Median treatment duration was 15.5 days (IQR: 13, 22) for nonsevere and 18.5 days (IQR: 13.5, 22) for severe VOD/SOS. Of 135 pediatric patients, VOD/SOS resolution occurred in 47/48 (98%) with nonsevere and 80/87 (92%) with severe VOD/SOS. Median treatment duration was 16 days (IQR: 13, 21) in nonsevere and 21 days (IQR: 12.5, 29) in severe VOD/SOS. Among adult patients with resolution of VOD/SOS, symptoms resolved after day 21 in 32% of patients with nonsevere and 31% of patients with severe VOD/SOS. A higher proportion of pediatric patients with severe (44%) compared with nonsevere VOD/SOS (15%) required >21 days of treatment for resolution of symptoms; correspondingly, 85% of pediatric patients with nonsevere and 56% with severe VOD/SOS had resolution with ≤21 days of defibrotide treatment. Kaplan-Meier (KM)-estimated survival at day 100 post-HCT among patients with severe VOD/SOS was 84% (95% confidence interval [CI]: 78%, 88%) in those who achieved VOD/SOS resolution and 14% (95% CI: 8%, 22%) in those who did not; among patients with nonsevere VOD/SOS, this was 94% (95% CI: 87%, 98%) and 35% (95% CI: 15%, 57%), respectively. Serious treatment-emergent adverse events (TEAEs) of interest occurred in 25% of patients with VOD/SOS resolution. In patients treated for ≤21 days and >21 days, respectively, the most common serious TEAEs of interest by category were infection (14% and 15%) and hemorrhage (12% and 13%). Among patients with VOD/SOS resolution, the most common causes of death were infection (severe: 11%; nonsevere: 2%) and graft-versus-host disease (severe: 6%; nonsevere: 2%). Conclusion Time to resolution of VOD/SOS tended to be longer in patients with severe versus nonsevere VOD/SOS, with many patients requiring >21 days of therapy to achieve resolution. A higher proportion of adult vs pediatric patients attained a CR >21 days after initiation of defibrotide treatment. Day 100 survival was higher in patients with VOD/SOS resolution versus without, regardless of severity, highlighting the importance of VOD/SOS resolution. The safety profile of defibrotide in the real-world setting was consistent with reports from previous studies, supporting the utility of defibrotide treatment per the prescribing information.

Bimekizumab safety in patients with moderate-to-severe plaque psoriasis: pooled data from up to 3 years of treatment in randomized phase III trials.

Patients with psoriasis require long-term management; therefore, understanding the long-term safety of new treatments, such as bimekizumab (BKZ), is crucial. To evaluate BKZ's 3-year safety profile in patients with moderate-to-severe plaque psoriasis. Three years of safety data were pooled from three phase III trials (BE VIVID, BE READY and BE SURE) and their ongoing open-label extension (BE BRIGHT). Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). In total, 1495 patients received at least one BKZ dose; total BKZ exposure was 3876.4 PY. The overall EAIR of TEAEs was 175.5/100 PY and decreased with longer exposure to BKZ. The most commonly reported TEAEs were nasopharyngitis, oral candidiasis and upper respiratory tract infection (EAIRs of 15.0/100 PY, 10.1/100 PY and 6.5/100 PY, respectively); 99.3% of oral candidiasis events were mild or moderate in severity, none were serious and few led to discontinuation. EAIRs of other TEAEs of interest were low, including serious infections (1.2/100 PY), adjudicated inflammatory bowel disease (0.2/100 PY) and laboratory elevations in aspartate aminotransferase or alanine aminotransferase (> 5 × upper limit of normal: 0.6/100 PY). In these analyses pooled across 3 years, no new safety signals were observed with longer exposure to BKZ. The vast majority of oral candidiasis events were mild or moderate in severity, as reported previously.

43978 Treatment-Emergent Adverse Events of Interest for Janus Kinase Inhibitors: Pooled Analysis of the 52-Week TRuE-V Phase 3 Studies of Ruxolitinib Cream Treatment for Vitiligo

43978 Treatment-Emergent Adverse Events of Interest for Janus Kinase Inhibitors: Pooled Analysis of the 52-Week TRuE-V Phase 3 Studies of Ruxolitinib Cream Treatment for Vitiligo

FDA analysis of toxicity profiles of oral TKIs recently approved for non-small cell lung cancer based on receipt of prior immune checkpoint inhibitor therapy.

9119 Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 are standard front-line therapy for advanced non-small cell lung cancer (NSCLC). Molecularly targeted tyrosine kinase inhibitors (TKIs) are standard of care for subsets of oncogene-driven NSCLC. Published literature suggests the possibility of increased toxicity in patients who receive ICIs followed by EGFR or ALK TKI treatment. However, the toxicity profile in patients who receive ICIs followed by TKIs with other genomic targets has not been well described. Methods: Marketing applications for TKIs in patients with NSCLC submitted to the Office of Oncologic Diseases between Jan 2019 to Dec 2022 were reviewed. Datasets were analyzed for demographics, treatment-emergent adverse events (TEAE), and prior anti-cancer therapies for TKI-treated patients in the primary efficacy population. Drug classes for which < 5% of patients received prior ICI were excluded. Grade 3-4 TEAE, serious adverse events (SAE), discontinuation TEAE and TEAE of interest (hepatotoxicity, rash, and interstitial lung disease [ILD]) were summarized. Results: 9 applications were identified and 2 were excluded. The remaining applications involved TKIs targeting EGFR exon 20 insertion, KRAS G12C, MET exon 14 skipping, and RET fusion alterations. Analyses included 867 patients; 61% received prior ICI therapy. Patient characteristics and results of analyses are presented in the table. In our pooled analysis, the incidence of Grade 3-4 AEs, SAEs, and hepatotoxicity were slightly higher in the prior ICI group, while the incidence of discontinuation TEAE, ILD, and rash were similar between groups. Analysis for hepatotoxicity was limited to reported AEs (did not include analysis of laboratory data). Review of toxicity data across individual drug classes did not show major differences compared to the overall results. Conclusions: Our analysis of safety data for newer TKIs with varied genomic targets does not appear to show excessive toxicity in patients with NSCLC who received prior ICI compared to those who did not. In future clinical trials evaluating TKIs in this population, inclusion of patients who have received prior ICI therapy should be considered when appropriate. [Table: see text]

OP35 Efficacy and safety outcomes up to ~4 years of treatment with filgotinib 200 mg among patients with Ulcerative Colitis: Results from the SELECTIONLTE study

Abstract Background Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). FIL 200 mg (FIL200) was effective in inducing and maintaining clinical remission vs placebo (PBO) and well tolerated in patients with UC in the randomized, phase 2b/3 SELECTION trial (NCT02914522).1 The efficacy and safety of continued FIL200 therapy are being assessed in the continuing SELECTION long-term extension (LTE) study. Methods The SELECTION programme comprises SELECTION and the associated LTE study (SELECTIONLTE; NCT02914535). In SELECTION, adults with moderately to severely active UC received induction (IND) FIL200, FIL 100 mg (FIL100) or PBO once daily for 11 weeks. Patients in clinical remission or with a Mayo Clinic Score (MCS) response at week 10 (responders) could enter the 47-week Maintenance (MNT) Study. SELECTIONLTE enrolled patients who completed IND and MNT (completers), patients who were not responders at IND week 10 (non-responders), and patients with disease worsening during MNT. This interim analysis assessed the efficacy and safety of open-label FIL200 through LTE week 144 in completers and LTE week 192 in non-responders, respectively, representing a total of 3.9 years of treatment each (completers: 58 + 144 weeks; non-responders 10 + 192 weeks). The cut-off date was 24 February 2022. Continuous measures of partial MCS (pMCS) and proportions of patients achieving the minimal clinically important difference (MCID) in total IBDQ score (≥16-point increase vs baseline) were assessed without imputation (as observed). Safety was assessed by the exposure-adjusted incidence rate per 100 patient-years of exposure (PYE) for treatment-emergent adverse events (TEAEs) and TEAEs of interest. Results This analysis included 148 completers and 372 non-responders (IND FIL100, n=212; IND FIL200, n=160). Among completers, the reductions in mean pMCS in SELECTION over weeks 0–10 were maintained up to LTE week 144 (Figure 1). In non-responders, mean pMCS decreased from LTE baseline to week 192 (Figure 2). High proportions of completers (>90%) and non-responders (>60%) achieved the MCID in IBDQ score; proportions were maintained over time (Table 1). Safety events among all patients treated with open-label FIL200 in the LTE study (total PYE=2055.5) are reported in Table 2. Conclusion: FIL200 was effective in maintaining symptomatic remission and health-related quality of life for up to ~4 years. No new safety signals were observed over ~4 years of treatment, and safety events were comparable with those seen in previous analyses.2 1. Feagan BG et al. Lancet 2021;397:2372–84. 2. Feagan BG et al. J Crohns Colitis 2022;16(Suppl1):i456–7.

Overall and Subgroup Results from the Third Interim Analysis of FIRE, a Real-World Study of Ibrutinib Treatment for CLL/SLL in France

Background: FIRE is a noninterventional, multicenter, observational study of patients with a confirmed diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with ibrutinib in France. Aim: The aim of the study is to collect real-world data to describe ibrutinib treatment patterns and assess its effectiveness and safety in CLL/SLL. Methods: This retrospective (ret) and prospective (pro) study started on May 12, 2016, and is planned to complete after ~6 years. Eligible patients were ≥ 18 years, with a confirmed diagnosis of CLL/SLL, and who initiated ibrutinib therapy on or after November 21, 2014, (date of ibrutinib commercialization) either in previously untreated patients with del17p and/or TP53 mutation, or in patients with relapsed or refractory disease R/R. Pro patients initiated ibrutinib treatment within 30 days of study start. Ret patients initiated ibrutinib treatment more than 30 days before inclusion in the study. Primary outcome measure was progression-free survival (PFS); secondary outcome measures included overall response rate (ORR), overall survival (OS), time to next treatment (TTNT), and safety. Ret-collected adverse events (AEs) included only those considered related to ibrutinib, whereas pro-collected AEs included all treatment-emergent AEs (TEAEs). Therefore, AEs are reported separately for each cohort. Total population effectiveness results were adjusted with left truncation. Patients were treated according to usual local clinical practice. Results: We report results from the third interim analysis for patients with previously untreated and R/R CLL/SLL, with a median follow-up of 47.2 months, and with a focus on subgroup analysis. The effectiveness and safety populations comprised 394 patients (pro, n = 200; ret, n = 194) and 400 patients (pro, n = 202; ret, n = 198), respectively. Median age at ibrutinib initiation was 72 years (range, 39.0-93.0); 66.2% were male; median time from diagnosis to ibrutinib initiation was 7 years (range, 0.0-35.0). Patients received 0 (15.0%), 1 (36.3%), 2 (28.2%), or ≥ 3 (20.6%) prior lines of therapy (LOT). At baseline, complete response (CR; 50.0%) or partial response (PR; 36.2%) were recorded with the last prior therapy. Most patients (87.4%) progressed following last prior therapy, and median time from progression to initiation of ibrutinib was 2.1 months (range, 0.0-100.1). Of reported patients (n = 399), massive or symptomatic lymphadenopathy and/or splenomegaly was the most common reason (42.6%) for initiating ibrutinib treatment. Median PFS was 47.5 months (48.5/51.6 months in pro/ret). LOT and age (≤ 75 vs > 75 years) were statistically significant predictive factors for PFS. In patients with 0, 1, 2, and ≥ 3 prior LOT, median PFS was: not estimable (NE), 53.9 months, 47.5 months, and 33.5 months, respectively (Figure). At 48 months’ follow-up, ORR was 91.4%. Median TTNT was 54.6 months (NE/54.8 months in pro/ret). Median OS was NE overall and in pro/ret cohorts. Main effectiveness outcomes according to prior LOT and age are presented in the Table. Serious TEAEs related to ibrutinib were reported in 25.8% and 28.2/23.2% in pro/ret cohorts, respectively. AEs led to dose interruption (37.6/29.8%), withdrawal (30.2/22.7%), or reduction (26.7/11.1%) in the pro/ret cohorts. TEAEs of interest in the pro/ret cohorts were infection (68.8/57.1%), diarrhea (27.2/15.7%), arthralgia/myalgia (25.2/13.1%), arrhythmia (15.8/13.6% [including atrial fibrillation {9.4%/7.1%}]), hypertension (14.9/14.6%), rash (10.4/8.1%), and major bleeding (7.9/1.5%). Ibrutinib was permanently discontinued in 234 patients (58.5%); reported reasons (n = 212) were mostly due to AEs (36.8%) and disease progression (31.1%). Conclusions: In this longer follow-up of the real-world FIRE study reflecting clinical practice in France, ibrutinib was shown to be an effective treatment for patients with CLL/SLL, and patients who received ibrutinib in earlier LOT achieved better PFS. The effectiveness and adverse event profiles are consistent with observations from clinical trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2–3 trial

SummaryBackgroundFexinidazole has been reported as an effective oral monotherapy against non-severe gambiense human African trypanosomiasis in a recent trial in adults. We aimed to assess the safety and efficacy of fexinidazole in children across all disease stages of gambiense human African trypanosomiasis.MethodsWe did a multicentre, single-arm, open-label, phase 2–3 trial at eight district hospitals in the Democratic Republic of the Congo. We recruited children with a Karnofsky score of more than 50, those aged 6 years to younger than 15 years, weighing 20 kg or more, and with confirmed gambiense human African trypanosomiasis (any stage). Children weighing 20 kg or more and less than 35 kg received oral fexinidazole of 1200 mg (two × 600 mg tablets) once per day for 4 days (days 1–4) followed by 600 mg (one × 600 mg tablet) once per day for 6 days (days 5–10). Children weighing 35 kg or more received oral fexinidazole of 1800 mg (three × 600 mg tablets) once per day for 4 days (days 1–4), followed by 1200 mg (two × 600 mg tablets) once per day for 6 days (days 5–10). The primary endpoint was fexinidazole treatment success rate 12 months after end of treatment. A rate greater than 80% was deemed acceptable and a target value of 92% was aimed for. Safety was assessed through routine monitoring. This study is completed and registered with ClinicalTrials.gov, number NCT02184689.FindingsBetween May 3, 2014, and Nov 22, 2016, we screened a total of 130 paediatric patients, of whom 125 (96%) received at least one dose of fexinidazole. All 125 patients (69 [55%] patients with stage 1, 19 [15%] with early stage 2, and 37 [30%] with late stage 2 gambiense human African trypanosomiasis) completed the 10-day treatment. Treatment success rate at 12 months was 97·6% (95% CI 93·1–99·5; 122 of 125 patients). The primary endpoint was met and the targeted value of 92% was exceeded. Treatment success at 12 months was elevated across all disease stages: 98·6% (95% CI 92·2–99·9; 68 of 69 patients) in stage 1, 94·7% (74·0–99·9; 18 of 19 patients) in early stage 2, and 97·3% (85·8–99·9; 36 of 37 patients) in late stage 2 gambiense human African trypanosomiasis. No new safety issues were observed beyond those found in adult trials. Overall, 116 (93%) of 125 patients reported 586 treatment-emergent adverse events, mainly mild or moderate. The most frequently reported treatment-emergent adverse events of interest during hospital admission were vomiting (86 [69%] of 125) and headache (41 [33%]). Seven (6%) of 125 patients had severe malaria, which was often accompanied by anaemia that was unrelated to fexinidazole. One patient died following dyspnoea and injury due to traumatic aggression 172 days after end of treatment, which was considered unrelated to fexinidazole or gambiense human African trypanosomiasis.InterpretationOral fexinidazole is a safe and effective first-line treatment option across all gambiense human African trypanosomiasis disease stages in paediatric patients.FundingThrough the Drugs for Neglected Diseases initiative: the Bill & Melinda Gates Foundation (USA), the Republic and Canton of Geneva (Switzerland), the Dutch Ministry of Foreign Affairs (Netherlands), the Norwegian Agency for Development Cooperation (Norway), the Federal Ministry of Education and Research through KfW (Germany), the Brian Mercer Charitable Trust (UK), and other private foundations and individuals from the human African trypanosomiasis campaign.TranslationFor the French translation of the abstract see Supplementary Materials section.

FIRE Study: Real-World Effectiveness and Safety of Ibrutinib in Clinical Practice in Patients with CLL and MCL

The FIRE study investigated the real-world effectiveness and safety of ibrutinib in prospectively observed patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) in France. Patients were mostly relapsed/refractory with high-risk features. First-line CLL/SLL patients had del17p and/or TP53 mutations. In this interim analysis, the median follow-up time for patients with CLL/SLL and MCL was 17.7 and 15.1 months, respectively. In the effectiveness populations for CLL/SLL (n = 200) and MCL (n = 59), the median progression-free survival was not estimable and 12.4 months, respectively; the 12-month overall survival rates were 88.5% and 65.8%, respectively. Treatment-emergent adverse events of interest for patients with CLL/SLL (n = 202) and MCL (n = 59) included: infections and infestations (53.5% and 32.2%), major bleeding (5.0% and 5.1%), and atrial fibrillation (5.9% and 8.5%); 135 (66.8%) and 20 (33.9%) patients were continuing treatment at the time of data cutoff. Future analyses will report on longer-term follow-up (Trial registration: ClinicalTrials.gov, NCT03425591. Registered 1 February 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03425591).

P907: CARFILZOMIB, DEXAMETHASONE, AND DARATUMUMAB (KDD) VS CARFILZOMIB AND DEXAMETHASONE (KD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): FRAILTY SUBGROUP ANALYSIS OF THE CANDOR STUDY

Background: Frailty scores based on age, comorbidities, and functional status can help identify frail patients (pts) at risk of higher rates of treatment-related toxicity or poor outcomes. An analysis of carfilzomib-treated pts in ASPIRE, ENDEAVOR, and ARROW found that efficacy and safety of carfilzomib regimens is consistent regardless of frailty status (Facon Blood Adv 2020). Aims: To compare efficacy and safety across frailty subgroups in pts with RRMM treated with KdD vs Kd in the phase 3 CANDOR study. Methods: This post hoc analysis used a planned interim readout (June 15, 2020) of CANDOR (NCT03158688). Pts were categorized as fit, intermediate (int), or frail based on a frailty score of 0, 1, or ≥2. Scoring used an algorithm based on the International Myeloma Working Group (IMWG) frailty index: the final score is based on age (0 if ≤75 years, 1 if 76-80 years, 2 if >80 years), modified Charlson Comorbidity Index (CCI [Facon Blood Adv 2020]) (0 if CCI ≤1, 1 if CCI >1), and Eastern Cooperative Oncology Group performance status (ECOG PS) (0 if ECOG PS=0, 1 if ECOG PS=1, and 2 if ECOG PS=2). Progression-free survival (PFS) was summarized descriptively, with hazard ratio (HR) and 95% CI estimated by stratified Cox proportional hazards model. Overall response rate (ORR) was summarized descriptively, with odds ratio (OR) and 95% CI estimated by Mantel-Haenszel method. Response and progression were assessed by the Onyx Response Computer Algorithm using IMWG criteria. Results: Frailty status was generally proportional between arms, with 27% and 35% classified as fit, 43% and 36% int, 25% and 27% frail, and 5% and 2% unknown for KdD and Kd, respectively. Although baseline characteristics of the overall population were generally balanced, more pts had prior transplant in the KdD vs Kd arm for int (65% vs 36%) and frail (41% vs 27%) subgroups, and in the frail subgroup fewer pts were lenalidomide exposed (37% vs 61%)/refractory (25% vs 46%) in the KdD vs Kd arm. Median duration of treatment for KdD vs Kd was 99 weeks (wks) vs 68 wks for fit pts, 82 wks vs 31 wks for int pts, and 51 wks vs 21 wks for frail pts. Median PFS in KdD vs Kd arms was not reached (NR) vs 17.6 months (HR 0.64, 95% CI 0.38–1.07) for fit, NR vs 11.1 months (HR 0.44, 95% CI 0.28–0.69) for int, and 18.5 vs 9.3 months (HR 0.66, 95% CI 0.38–1.14) for frail pts. ORR for KdD vs Kd arms was 89% vs 89% (OR 1.09, 95% CI 0.35–3.38) for fit pts, 87% vs 70% (OR 2.95, 95% CI 1.31–6.62) for int pts, and 75% vs 54% (OR 2.39, 95% CI 1.09–5.22) for frail pts (Figure). Any grade treatment-emergent adverse events (TEAEs) occurred in >95% of pts across arms and subgroups. Grade ≥3 TEAEs occurred in 87% (KdD) and 70% (Kd) of fit pts, 84% and 71% of int pts, and 91% and 90% of frail pts. Fatal TEAEs occurred in 4% and 2% of fit pts, 11% and 9% of int pts, and 16% and 8% of frail pts in the KdD and Kd arms. Carfilzomib was discontinued due to TEAEs in 25% vs 17% of fit pts, 22% vs 29% of int pts, and 35% vs 23% of frail pts. Among TEAEs of interest, acute renal failure occurred in 0 fit pts, 3% vs 14% of int pts, and 8% vs 5% of frail pts, and infusion reactions occurred in 16% vs 2% of fit pts, 13% vs 4% of int pts, and 14% vs 13% of frail pts in the KdD vs Kd arms (Table). Image:Summary/Conclusion: Consistent with previous findings of the efficacy and safety benefits of KdD, a PFS benefit with KdD vs Kd was observed across frailty subgroups, without increased toxicity. The clinically meaningful ORR benefit in the frail subgroup may help physicians evaluate treatment options in this challenging group.

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study.

Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in the pivotal ZUMA-2 study of KTE-X19 in relapsed/refractory MCL are reported, including for subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics. Patients with relapsed/refractory MCL (one to five prior therapies, including prior BTKi exposure) received a single infusion of KTE-X19 (2 × 106 CAR T cells/kg). After a median follow-up of 35.6 months, the objective response rate among all 68 treated patients was 91% (95% CI, 81.8 to 96.7) with 68% complete responses (95% CI, 55.2 to 78.5); medians for duration of response, progression-free survival, and overall survival were 28.2 months (95% CI, 13.5 to 47.1), 25.8 months (95% CI, 9.6 to 47.6), and 46.6 months (95% CI, 24.9 to not estimable), respectively. Post hoc analyses showed that objective response rates and ongoing response rates were consistent among prespecified subgroups by prior BTKi exposure or high-risk characteristics. In an exploratory analysis, patients with prior bendamustine benefited from KTE-X19, but showed a trend toward attenuated T-cell functionality, with more impact of bendamustine given within 6 versus 12 months of leukapheresis. Late-onset toxicities were infrequent; only 3% of treatment-emergent adverse events of interest in ZUMA-2 occurred during this longer follow-up period. Translational assessments revealed associations with long-term benefits of KTE-X19 including high-peak CAR T-cell expansion in responders and the predictive value of minimal residual disease for relapse. These data, representing the longest follow-up of CAR T-cell therapy in patients with MCL to date, suggest that KTE-X19 induced durable long-term responses with manageable safety in patients with relapsed/refractory MCL and may also benefit those with high-risk characteristics.

Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL

This open-label, multicenter, single-arm, phase 2 study assessed the safety and efficacy of blinatumomab consolidation therapy in adult patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL; International Prognostic Index 3–5 and/or double-/triple-hit or double MYC/BCL-2 expressors) who achieved complete response (CR), partial response (PR), or stable disease (SD) following run-in with 6 cycles of R-chemotherapy (NCT03023878). Of the 47 patients enrolled, 28 received blinatumomab. Five patients (17.9%) experienced grade 4 treatment-emergent adverse events of interest (neutropenia, n = 4; infection, n = 1). Two deaths reported at the end of the study were unrelated to treatment with blinatumomab (disease progression, n = 1; infection, n = 1). 3/4 patients with PR and 4/4 patients with SD after R-chemotherapy achieved CR following blinatumomab. Consolidation with blinatumomab in patients with newly diagnosed, high-risk DLBCL who did not progress under R-chemotherapy was better tolerated than in previous studies where blinatumomab was used for treatment of patients with lymphoma.

P491 Efficacy and safety outcomes of long-term treatment with filgotinib 200 mg among patients with Ulcerative Colitis: An interim analysis of SELECTIONLTE

Abstract Background Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor in development as an ulcerative colitis (UC) therapy. In the phase 2b/3 SELECTION trial, FIL 200 mg (FIL200) was well tolerated and effective in inducing and maintaining clinical remission vs placebo (PBO) in patients with UC.1 We assessed the efficacy and safety of continued FIL200 therapy in the SELECTION long-term extension (LTE) study. Methods The SELECTION programme comprised SELECTION (NCT02914522)1 and an ongoing LTE study, SELECTIONLTE (NCT02914535). Adults with moderately to severely active UC received induction (IND) FIL200 or FIL100 or PBO for 11 weeks in SELECTION. Patients in clinical remission or Mayo Clinic Score (MCS) response at week 10 (responders) could enter the 47-week Maintenance (MNT) Study. Patients who completed the SELECTION IND and MNT studies (completers), IND non-responders and patients with disease worsening during MNT could enter SELECTIONLTE. This interim analysis assessed the efficacy of open-label FIL200 among completers and non-responders in SELECTIONLTE up to LTE weeks 48 and 96, respectively. Partial MCS (pMCS) and achievement of the minimal clinically important difference (MCID) in total health-related quality of life (HRQoL) IBDQ score (≥16-point increase vs baseline) were assessed over time. Exposure-adjusted incidence rates per 100 patient-years of exposure (PYE) of treatment-emergent adverse events (TEAEs) and TEAEs of interest were assessed in patients treated with open-label FIL200 in the LTE. Results These analyses included 147 completers and 372 non-responders (IND FIL200, n=160; IND FIL100, n=212). Data were available for 136 completers at LTE week 48 and for 97 IND FIL200 and 139 IND FIL100 non-responders at LTE week 96. Among completers, the mean pMCS reductions observed in SELECTION were maintained up to LTE week 48 (Figure 1). Among IND FIL200 and FIL100 non-responders, mean pMCS decreased from LTE baseline to week 96 (Figure 2). The proportion of patients achieving the MCID in total IBDQ score increased over time among completers (IND week 10, 90.4%; LTE week 48, 96.1%) and IND FIL200 non-responders (LTE week 48, 60.6%; LTE week 96, 66.7%) (Table 1). Safety events among patients treated with open-label FIL200 in the LTE study (total PYE, 970.9) to the date analysed are reported in Table 2. Conclusion FIL200 was effective in maintaining long-term improvements in UC symptoms and HRQoL among patients who completed SELECTION. Among non-responders, initiating open-label FIL200 in the LTE study led to improvements in UC symptoms and HRQoL that were sustained over time. Safety events were as expected in the LTE study based on initial data. Reference 1. Feagan BF et al. Lancet 2021;397:2372–84.

Abstract CT160: Safety of selpercatinib for RET-altered advanced solid tumors: a post hoc analysis of LIBRETTO-001

Abstract Introduction: Selpercatinib, approved by FDA in May 2020 is a highly selective and potent RET inhibitor which has demonstrated antitumor activity in patients (pts) with RET-altered non-small-cell lung cancer and thyroid cancer. To further characterize clinical safety, we analyzed the timing of selected treatment-emergent adverse events (TEAEs) as well as long-term use of selpercatinib. Methods: Pts with RET-fusion positive or RET-mutant tumors who received at least 1 dose of selpercatinib, as part of the LIBRETTO-001 study, were included in this analysis (data-cut off 19 Dec 2019; NCT 03157128). Median time to onset, dose reduction, and discontinuation due to TEAEs were evaluated for relevant common TEAEs (≥25% of pts) and TEAEs of special interest. TEAE data were also analyzed according to time exposed to treatment at cutoff (<12 or ≥12 months). Results: A total of 702 pts were included in the analysis and 99% experienced ≥1 TEAE (any grade). At cutoff, median time on treatment was 8.7 mo, with 78% continuing to receive selpercatinib. Common TEAEs and TEAEs of interest are summarized (median time to onset, dose reduction, and discontinuation due to TEAEs) in the table. 466 (66.4%) pts received treatment for <12 months, whereas 236 (33.6%) pts received treatment for ≥12 months. Similar rates of grade ≥3 TEAEs were observed across the two exposure groups, 271 (58.2%) pts and 145 (61.4%) pts on treatment for <12 months and ≥12 months, respectively. 138 (29.6%) pts on treatment <12 months and 81 (34.3%) pts on treatment ≥12 months underwent dose reductions due to TEAEs. 32 (6.9%) pts on treatment <12 months and 5 (2.1%) pts on treatment ≥12 months discontinued treatment due to TEAEs. Conclusion: Most TEAEs had a median onset within the first month of treatment, with TEAEs minimally impacting a patient's ability to receive selpercatinib. In these analyses, no new safety concerns were identified in patients on treatment for <12 months or ≥12 months. Relevant TEAEs of interest by decreasing frequency in any grade in ≥25% of patients and TEAEs of interest (N = 702)TEAE(consolidated terms)Any Grade TEAEn (%)Median time (weeks) to first occurrence (range)Leading to dose reductionn (%)Leading to drug discontinuationn (%)Dry Mouth273 (38.9)2.9 (0.1-107.9)5 (0.7)0 (0.0)Diarrhea257 (36.6)8.0 (0.1-99.9)11 (1.6)0 (0.0)Hypertension252 (35.9)History of hypertension114 (39.4)2.5 (0.1-83.0)5 (1.7)0 (0.0)No history of hypertension138 (33.4)2.2 (0.1-60.0)4 (1.0)0 (0.0)AST increased210 (29.9)4.1 (0.1-111.1)39 (5.6)2 (0.3)ALT increased201 (28.6)4.1 (0.1-79.7)45 (6.4)3 (0.4)Constipation178 (25.4)4.4 (0.1-90.4)2 (0.3)0 (0.0)QTc Prolongation118 (16.8)3.5 (0.1-92.0)16 (2.3)0 (0.0)Hypersensitivity30 (4.3)1.7 (0.9-77.0)20 (2.8)3 (0.4)Rash191 (27.2)9.3 (0.1-110.4)15 (2.1)1 (0.1)Edema242 (34.5)9.8 (0.1-109.9)7 (1.0)0 (0.0)Fatigue246 (35.0)5.4 (0.1-9918 (2.6)2 (0.3)N, number of subjects in the population; n, number of subjects in the specified category; TEAE, treatment-emergent adverse event. AST, aspartate transaminase; ALT, alanine aminotransferase; QTc, corrected QT. Citation Format: Todd M Bauer, Benjamin Besse, Herbert H F Loong, Bruce Robinson, Victoria Soldatenkova, Catherine Elizabeth Muehlenbein, Bente Frimodt-Moller, Caroline E McCoach. Safety of selpercatinib for RET-altered advanced solid tumors: a post hoc analysis of LIBRETTO-001 [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 CT160.

Final Primary Results from the Defifrance Registry Study: Effectiveness and Safety of Defibrotide in the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication that occurs after hematopoietic cell transplantation (HCT) conditioning. In its most severe form, VOD/SOS is associated with multi-organ failure (MOF) and a mortality rate of >80% if untreated. Defibrotide is approved for the treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in adult and pediatric patients in the United States and severe hepatic VOD/SOS post-HCT in patients aged >1 month in the European Union. The DEFIFrance study collected real-world data on the safety and effectiveness of defibrotide in France. This analysis presents final primary data on the subgroup of DEFIFrance patients who received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT. This post-marketing study collected retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centers in France from July 15, 2014 to March 31, 2020. VOD/SOS severity was categorized using European Society for Blood and Marrow Transplantation criteria (adults) or study steering committee member adjudication (pediatric patients). The primary endpoints included Kaplan-Meier (KM)-estimated Day 100 (post-HCT) survival and Day 100 complete response (CR; total serum bilirubin <2 mg/dL and MOF resolution per investigators' assessment) in patients with severe/very severe VOD/SOS post-HCT. Secondary endpoints included evaluation of adverse events (AEs) of interest, such as hemorrhage, coagulopathy, injection-site reactions, infections, and thromboembolic events, irrespective of their relationship to treatment. Of the 775 defibrotide-treated patients included in the study analysis, 250 received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT (severe: 119 [48%]; very severe: 131 [52%]). The median patient age was 45 years (range: 5 months, 74 years) and 52 (21%) patients were less than 18 years of age. A total of 219 (88%) patients had received allogeneic HCT and 95 (38%) patients had an unrelated donor. The Day 100 KM-estimated survival was 58% (95% confidence interval [CI]: 52%, 64%) in patients with severe/very severe VOD/SOS post-HCT. The estimated Day 100 survival rate was higher in patients with severe (74% [95% CI: 65%, 81%]) versus very severe (43% [95% CI: 35%, 52%]) VOD/SOS. Among patients with severe/very severe VOD/SOS post-HCT, the CR rate at Day 100 was 53% (95% CI: 47%, 59%). The Day 100 CR rate was higher in patients with severe (68% [95% CI: 60%, 77%]) versus very severe (39% [95% CI: 30%, 47%]) VOD/SOS. Treatment emergent AEs of interest occurred in 41% of patients with severe/very severe VOD/SOS, with infection (23%) and bleeding (17%) being the most commonly reported. The DEFIFrance study represents the largest collection of real-world data on the use of defibrotide. The effectiveness and safety observed in this study build upon prior studies supporting the utility of defibrotide for treating severe/very severe VOD/SOS post-HCT in a real-world setting. Among patients receiving defibrotide for VOD/SOS post-HCT, outcomes were better in patients with severe versus very severe disease, highlighting the importance of early diagnosis and treatment of VOD/SOS before patients reach the most severe stage of VOD/SOS. Disclosures Mohty: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria. Labopin:Jazz Pharmaceuticals: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria. Renard:Jazz Pharmaceuticals: Research Funding. Jubert:Jazz Pharmaceuticals: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Bouvatier:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Dalle:Bellicum: Consultancy, Honoraria; Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Consultancy, Honoraria; Gilead: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orchard: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Peffault De Latour:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

HORIZON (OP-106): Melflufen Plus Dexamethasone (dex) in 55 Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM) with Extramedullary Disease (EMD)-Subgroup Analysis

HORIZON (OP-106): Melflufen Plus Dexamethasone (dex) in 55 Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM) with Extramedullary Disease (EMD)-Subgroup Analysis

O09 Pooled safety analyses from Phase 3 studies of filgotinib in patients with RA

Abstract Background Filgotinib (FIL) is an oral, selective janus kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, summarized, summarized studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24). Methods The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to standard of care. W24 safety data from all studies were aggregated and ummarized. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities. Results 3,452 patients were evaluated; 2,088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups. Conclusion Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD. Disclosures D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. K. Winthrop: Grants/research support; Received grants for clinical research from Bristol-Myers Squibb Company and Insmed Incorporated. Other; Received support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly & Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, and UCB. M.C. Genovese: Other; Gilead Sciences Inc., Galapagos NV, AbbVie Inc. Eli Lilly and Company, Pfizer. B.G. Combe: Honoraria; Honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. Y. Tanaka: Honoraria; Received from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly and Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Received grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, and Ono. A. Kivitiz: Consultancies; Consultant for AbbVie, Celgene, Horizon, Janssen, Merck, Novartis, Pfizer, UCB, Genzyme,Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim and Flexion. Shareholder/stock ownership; Shareholder of Novartis. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. L. Ye: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Gilead Sciences, Inc. Shareholder/stock ownership; Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. E. Keystone: Consultancies; AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer, PuraPharm, Sandoz,, Sanofi-Aventis, Sanofi- Genzyme Samsung Bioepsis, and UCB. Other; AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer, PuraPharm, Sandoz,, Sanofi-Aventis, Sanofi-Genzyme, Samsumg Bioepsis, and UCB. R. Westhovens: Corporate appointments; An investigator and advisor for Celltrion and Galapagos/Gilead. W. Rigby: Consultancies; Consultancy for Gilead. G.R. Burmester: Consultancies; Consultancy from AbbVie, Gilead, Eli Lilly, and Pfizer. Honoraria; Honoraria from AbbVie, Gilead, Eli Lilly, and Pfizer.

Clinical Outcomes and Characteristics of Patients (pts) with FLT3–Internal Tandem Duplication (FLT3-ITD)–Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Undergoing Hematopoietic Stem Cell Transplant (HSCT) after Quizartinib (Q) or Salvage Chemotherapy (SC) in the Quantum-R Trial

<h3>Introduction</h3> In QuANTUM-R, the once-daily, oral, highly potent and selective FLT3 inhibitor Q improved clinical benefit vs SC (median overall survival [mOS], 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); <i>P</i> = .02]) in R/R <i>FLT3</i>-ITD AML (NCT02039726). Before randomization, 25% (Q) and 23% (SC) of pts had 1 prior HSCT. <h3>Objective</h3> To describe post hoc analyses in pts who underwent subsequent HSCT during QuANTUM-R. <h3>Methods</h3> Pts with <i>FLT3</i>-ITD R/R AML received Q (60 mg [30-mg lead-in]) or SC. Pts in the Q arm could resume Q 30-100 d after HSCT. Decisions to proceed to HSCT and resume Q after HSCT were made per investigator discretion/institutional policy. <h3>Results</h3> Of 367 randomized pts, 85 in the Q arm underwent any subsequent HSCT (allogeneic HSCT [allo-HSCT], 84 [6 with and 78 w/o additional AML therapy]; autologous HSCT, 1), and 19 in the SC arm underwent any HSCT (5 with and 14 w/o additional AML therapy]). Q + SC pooled data showed a longer mOS (95% CI) in 104 pts with any HSCT vs 263 w/o (12.2 [10.0-24.1] vs 4.4 [4.1-4.9] mo; <i>P</i> < .0001; Fig 1); 1-year OS rates were 50% vs 13%. Among pts preselected for low-intensity therapy, 13/57 in the Q arm and 0/29 in the SC arm underwent any HSCT. Q + SC pooled data also showed a longer mOS (95% CI) in pts with a composite complete remission (CRc) as last recorded response before allo-HSCT vs pts w/o CRc (20.1 [11.7-NA] vs 8.8 [7.0-11.4] mo). Regardless of treatment, mOS was longer with any HSCT vs w/o (Q, 11.9 [10.2-25.1] vs 4.5 [4.1-5.4] mo; SC, 12.7 [6.1-NA] vs 4.0 [2.7-5.0] mo); respective 1-year OS rates were 50% vs 13% and 51% vs 12%. In the Q arm, mOS (95% CI) was longer in pts with a best response of CRc who resumed Q after allo-HSCT (27.1 [18.2-NA] mo) vs pts not resuming Q (5.4 [4.7-11.4] mo; Fig 2). In 48 pts (62%) in the Q arm resuming Q after allo-HSCT, median time from allo-HSCT to Q resumption was 65 d (range, 30-106 d). Four pts (5%) in the Q arm died < 30 d after allo-HSCT. As of 2/22/2018, 46/78 pts in the Q arm (59%) and 9/14 pts in the SC arm (64%) with allo-HSCT w/o additional AML therapy died, mostly due to AML progression (Q, 31 [40%]; SC, 7 [50%]). The frequency of treatment-emergent adverse events (TEAEs) and TEAEs of interest was similar in pts resuming Q after allo-HSCT and in the overall Q population. <h3>Conclusion</h3> Independent of HSCT, Q improved survival vs SC in pts with <i>FLT3</i>-ITD R/R AML in QuANTUM-R. Q + SC pooled analyses showed longer survival in pts with HSCT vs pts w/o and in pts with CRc before allo-HSCT. Survival in transplanted pts was similar in both arms, indicating that HSCT-eligible pts received transplants appropriately, and the higher HSCT rate in the Q arm was beneficial. In pts preselected for low-intensity SC at study entry, 13 were able to undergo HSCT after Q treatment. Q resumption after HSCT was associated with better survival outcomes and was tolerable. These data illustrate the value of using Q to target the <i>FLT3</i>-ITD mutation as a part of the overall treatment sequence in pts with <i>FLT3</i>-ITD R/R AML.

P597 Pooled safety analyses from Phase 3 studies of filgotinib in patients with rheumatoid arthritis

Abstract Background Filgotinib (FIL) is an oral, selective Janus Kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, randomised, multicentre studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24). Methods The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to a standard of care. W24 safety data from all studies were aggregated and summarised. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities. Results 3452 patients were evaluated; 2088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups. Conclusion Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD.

Clinical Outcomes and Characteristics of Patients (pts) with FLT3-Internal Tandem Duplication (FLT3-ITD)-Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Undergoing Hematopoietic Stem Cell Transplant (HSCT) after Quizartinib (Q) or Salvage Chemotherapy (SC) in the Quantum-R Trial

Clinical Outcomes and Characteristics of Patients (pts) with FLT3-Internal Tandem Duplication (FLT3-ITD)-Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Undergoing Hematopoietic Stem Cell Transplant (HSCT) after Quizartinib (Q) or Salvage Chemotherapy (SC) in the Quantum-R Trial