Common Reason For Discontinuation Research Articles

Safety and Efficacy of Parsaclisib in Combination with Rituximab, Bendamustine + Rituximab, or Ibrutinib in Patients with Previously Treated B-Cell Lymphoma: Analysis of a Phase 1 Dose-Finding Study (CITADEL-112)

Background: Rituximab (RIT)-based chemoimmunotherapy regimens are backbone treatment for indolent (follicular, marginal zone) and aggressive (diffuse large B-cell, mantle cell) B-cell lymphomas. For relapsed or refractory (R/R) disease, anti-CD20 antibodies can be combined with chemotherapy or targeted therapies, such as inhibitors of Bruton's tyrosine kinase (eg, ibrutinib) and phosphoinositide 3-kinase (PI3K). Parsaclisib is a potent and highly selective next-generation PI3Kδ inhibitor. In a preliminary safety analysis of CITADEL-112 (NCT03424122), an open-label phase 1 study of parsaclisib plus investigator choice standard of care (RIT, RIT + bendamustine [BEN], or ibrutinib [IBR]) in patients (pts) with R/R B-cell lymphoma, manageable tolerability was observed (Sancho JM, et al. HemaSphere 2022;6 Suppl 3:P1102). Here we present updated safety and initial efficacy data from CITADEL-112. Methods: Enrolled pts were ≥18 years and had histologically confirmed DLBCL, FL, MCL, or MZL, ECOG performance status of 0-2, were R/R to ≥1 (≥2 for FL) prior systemic therapy, and ineligible for stem cell transplantation. Pts received parsaclisib 20 mg orally once daily (QD) for 8 weeks then 20 mg once weekly (QW) in combination with either RIT 375 mg/m2 IV QW for 4 doses in cycle 1 (± an additional 4 QW doses) in Cohort A, or RIT 375 mg/m2 IV on day 1 + BEN 90 mg/m2 on day 1 and day 2 of each 28-day cycle for ≤6 cycles in Cohort B, or IBR 560 mg QD in Cohort C. A 3+3 design with dose de-escalation identified the maximum tolerated dose of QD parsaclisib within each treatment regimen independently. Pts received treatment until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was safety and tolerability. Investigator-determined objective response rate (ORR) and duration of response (DOR) were exploratory endpoints. Results: At data cutoff (January 14, 2022), 50 pts were treated (16 pts each in Cohorts A and C, 18 pts in Cohort B) and 5 pts were ongoing treatment (all in Cohort B). Most pts had received ≥2 prior systemic treatments; the most common disease subtypes were FL in Cohort A and DLBCL in Cohorts B and C (Table 1). Median (range) dose of QD parsaclisib was 20.0 (13.3-20.0), 17.9 (2.8-20.0), and 20.0 (7.1-20.0) mg/day in Cohorts A, B, and C, respectively, and median (range) overall duration (QD+QW) of parsaclisib treatment was 5.1 (0.5-22.9), 9.3 (0.5-33.7), and 9.3 (0.6-37.7) months. The most common reasons for discontinuation were progressive disease (75.0%, 44.4%, and 56.3% in Cohorts A, B, and C, respectively) and adverse events (AEs; 12.5%, 16.7%, and 6.3%, respectively). One pt in Cohort B experienced a dose-limiting toxicity of grade 4 neutropenia for 14 days. All pts experienced ≥1 treatment-emergent AE (TEAE); most common any-grade and grade ≥3 TEAEs are shown in Table 2. Grade ≥3 and serious TEAEs were experienced by 75.0% and 37.5% of pts, respectively, in Cohort A, 88.9% and 33.3% of pts in Cohort B, and 62.5% and 50.0% of pts in Cohort C. Serious TEAEs occurring in >1 pt were COVID-19, diarrhea, and pneumonia (n=2 each) in Cohort A, and atrial fibrillation (n=2) in Cohort C. TEAEs with fatal outcome occurred in 2 pts in Cohort A (COVID-19 and COVID-19 pneumonia [n=1], interstitial lung disease [n=1]) and 1 pt in Cohort C (COVID-19 pneumonia, septic shock, acute kidney injury, respiratory failure). TEAEs leading to discontinuation of parsaclisib occurred in 2 pts in Cohort A (diarrhea, streptococcal pneumonia [n=1 each]), 3 pts in Cohort B (neutropenia, maculopapular rash [n=1 each], diarrhea and renal failure [n=1]), and 1 pt in Cohort C (thrombocytopenia). TEAEs leading to parsaclisib dose interruption or reduction occurred in 75.0% and 18.8% of pts, respectively, in Cohort A, 66.7% and 27.8% of pts in Cohort B, and 56.3% and 18.8% of pts in Cohort C. ORRs (95% confidence interval [CI]) were 81.3% (54.4-96.0), 55.6% (30.8-78.5), and 50.0% (24.7-75.3) for Cohorts A, B, and C, respectively; 18.8%, 33.3%, and 12.5% of pts had a complete metabolic response/complete response, respectively (Table 1). Median (95% CI) DOR was 5.2 months (1.7-15.8) for Cohort A, not reached (12.1-not evaluable [NE]) for Cohort B, and 13.4 months (0.7-NE) for Cohort C. Conclusion: Parsaclisib 20 mg QD for 8 weeks followed by 20 mg QW in combination with RIT, RIT+BEN, or IBR in pts with R/R B-cell lymphomas had a manageable tolerability profile with no unexpected safety concerns, and demonstrated promising efficacy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pooled Safety Analysis from Phase I-III Studies for Patients with Hematological Malignancies Treated with the PI3K Inhibitor Copanlisib

Introduction: As of 2021, four phosphatidylinositol 3-kinase (PI3K) inhibitors had received accelerated approval by the FDA for treatment of patients (pts) with indolent follicular lymphoma (FL) having received ≥2 systemic therapies. Recently, during confirmatory studies, three of the PI3K inhibitors have been voluntarily withdrawn over concerns for toxicities impacting overall survival and this issue was the focus of an Oncologic Drugs Advisory Committee (ODAC) meeting in April 2022. Copanlisib is the only PI3K inhibitor currently available for treatment of FL and is distinguished by being administered intravenously on an intermittent schedule. We report here a comprehensive pooled analysis of copanlisib safety with long-term follow-up from 10 completed Phase I-III studies in pts with hematologic malignancies. Methods: Pts with hematologic malignancies treated with copanlisib monotherapy in completed open-label Phase I or II studies and a randomized, placebo-controlled Phase III in combination with rituximab were included. Copanlisib 60 mg (i.v.) was administered intermittently on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. AEs were reported using MedDRA version 24.1 and assessed by duration of treatment in 6-month intervals or time of onset (worst grade or new AEs occurring ≤180 days [d], 181-360 d, 361-540 d, 541-720 d, or ≥721 d). Results: A total of 684 pts received copanlisib and were evaluable for safety (data cut-off Feb 2022). Median age was 64 years (range 22-93). A total of 51% of pts had a history of FL, 14% MZL, and 10% DLBCL. More than half (54%) were treated with copanlisib for less than 6 months, whereas 27% were treated for >12 months and 13% >2 yrs. The mean overall duration of treatment was 10.9 months (range 0.2-80 months). 24% of pts had at least one dose reduction and 73% had at least one dose interruption or delay (mean duration 3 days). Copanlisib-related treatment-emergent AEs (TEAEs) were reported in 92% of pts; 55% of pts had TEAEs of worst grade [g] 3, and 24% had TEAEs of worst g4. The most common reasons for discontinuation were progression (41%), AE not associated with clinical disease progression (29%) and withdrawal by subject (11%). The most common (≥10%) copanlisib-related TEAEs (% all-grade/g3/g4) were hyperglycemia (58/37/6), hypertension (42/33/0), diarrhea (23/4/0), neutrophil count decreased (20/7/7), neutropenia (19/8/7), nausea (17/0.3/0), white blood cell count decreased (13/5/0.6), fatigue (13/1/0), and anemia (11/3/0). Hyperglycemia and hypertension, both of which were infusion related and transient, had the highest incidence in the first 180 days of treatment. For diarrhea, pts treated for longer duration were more likely to have experienced diarrhea, but g3 events were constant per 6-month onset of event interval (2.2/2.5/3.2/0.8/3.3%). For AEs of interest, the incidence of colitis was low (0.9%; 6 pts: 2 g1, 3 g3 and 1 g4) as was the overall incidence of pneumonitis (6/2/0.6; one g5) with all the g4 events occurring <180 days. The occurrence of late onset AEs of increasing severity has been an issue with orally administered PI3K inhibitors. The greater exposure of pts to copanlisib with longer treatment notwithstanding, we examined the incidence and severity of AEs in pts treated ≤6 months, 6-12 months and >12 months, by overall duration of treatment and by interval of onset (Table) to ascertain the timing and severity of AEs. For hyperglycemia and hypertension, the overall incidence rate was similar for pts treated ≤6 months, 6-12 months and >12 months but was mostly accounted for higher rates day 1-180. Diarrhea was higher in pts treated >12 months, but mostly due to low grade events. There was a trend for a higher incidence of neutropenia and/or neutrophil count decrease depending on treatment duration, but infections remained low. A total of 50 (7%) pts died within 35 days of discontinuing copanlisib, with 18 (2.6%) due to progressive disease (PD) and 9 (1.3%) AEs related to PD, and 20 (2.9%) AEs not associated with clinical progression. Copanlisib-related g5 (death) TEAEs were reported in 10 pts (1.5%), with 8 events in pts treated <6 months; infection-related AEs reported in 5 pts. Conclusions: Based on this expanded safety dataset with long-term treatment of copanlisib, there is no evidence of late-onset toxicities or worsening of severity of TEAEs. No new or unexpected safety issues were identified. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ruxolitinib for Myelofibrosis in Resource Limited Settings : A Slip between the Cup and the Lip

Background and Objective:Ruxolitnib, an orally bioavailable non-specific JAK inhibitor is a novel drug used for treating myelofibrosis by targeting the unique disease biology and has significantly reduced symptomatic burden in these patients. In resource limited countries, the data on post marketing experience with this relatively novel agent is limited. The major objectives of this study was to examine the challenges encountered with the use of Ruxolitinib in our resource limited setting. Methods:Patients with confirmed diagnosis of myelofibrosis and initiated on ruxolitinib therapy consecutively during the time period between December 2013 to March 2019 at our institute were included in the study. The data was collected from electronic medical records over a period of 12 months from March 2020 to March 2021. Results:This retrospective analysis included forty six patients and their baseline characteristics are summarized in Table 1. Twenty five (54.3%) patients received lower than the recommended dose for the corresponding platelet count. On response assessment, the mean MPN SAF ISS score showed reduction from 30 (6-64) to 15 (2-38).Among the 36 patients with splenomegaly documented in records, a spleen response below costal margin of <5cm was seen in 2 (5.5%), 5 - 10cm in 9 (25%) and >10cm in 22 (61.1%) patients. . The patients were followed up for a median of 29.5 months (0-76 months) after Ruxolitinib initiation.At the time of data locking, 12 (26%) patients were still on ruxolitinib, 13 (28.2%) patients were lost to follow up and 7 (15.2%) patients died. Rest of the fourteen (30.4%) patients discontinued ruxolitinib, the reasons being financial constraints in 7 (50%), disease progression in 3 (21.4%), haematological toxicity in 2 (14.2%) and intolerance due to non-haematological causes in 2 (14.2%). Haematological adverse events that necessitated dose reduction or cessation of drug were anemia and thrombocytopenia. The serious non-hematological adverse events were renal dysfunction, pancreatitis, COVID infection, DIC and pulmonary alveolar haemorrhage in one patient each and two cases of active tuberculosis. Seven (15.2%) patients died while on therapy or shortly after discontinuing ruxolitinib. The causes of death were pulmonary alveolar haemorrhage, disease progression, disseminated intravascular coagulation post cardiac valve surgery, pneumonia complicated by sepsis/ hemophagocytic lymphohistiocytosis (HLH) and COVID infection. Among these, 2 patients died within one month of stopping ruxolitinib. The possibility of ruxolitinib discontinuation syndrome (RDS) was considered retrospectively in these patients. The overall mean survival time was 145.4 ±16 months (95% CI: 114 - 176.8months). Discussion:At the time of last follow-up, more than half of the patients in our study group had either discontinued therapy or were lost to follow up. The most common reason for discontinuation was financial burden, the other reasons being disease progression and intolerance. In our setting, the patients entail an annual cost of approximately 2560 USD, 4530 USD and 4770 USD for 5mg BD, 15mg BD and 20mg BD respectively within patient assisted programs and much higher outside these programs. In a country like India with a nominal Gross Domestic Product (GDP) per capita of around 2191 USD, this not only reflects the high cost of the drug but also the discordant pricing of the different doses resulting in opting for lower doses. The financial burden of the drug is also reflected in the NICE Appraisal Committee recommendation that though ruxolitinib is clinically effective, it is not cost effective for symptomatic therapy CONCLUSION In spite of having a good symptom response, many of our patients discontinued the drug because of its "financial toxicity". In developing economies, better access to the drug and doing away with suboptimal doses need to be addressed so that the target population can reap its therapeutic effect in entirety. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 13593: Rates of Acute Kidney Injury or Discontinuation After SGLT2 Inhibitor Initiation in a Real-World Cohort of Patients With Heart Failure With Reduced Ejection Fraction

Background: SGLT2 inhibitors (SGLT2i) decrease mortality and risk of hospitalizations in patients with HFrEF. SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate real-world rates of acute kidney injury (AKI) in our clinical setting that includes patients concurrently receiving high doses of loop diuretics. Methods: We abstracted patient level data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting in the University of Michigan (1/7/2016 - 2/7/2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. Secondary end points consisted of diuretic dose reduction, change in potassium, change in serum creatinine (SCr), and other side effects not requiring discontinuation. Results: The majority of patients were male (64%) with a mean LVEF of 27%. A total of 104 (52%) patients had diabetes mellitus. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. Twenty-two (11%) patients had AKI and 18 patients (9%) discontinued their SGLT2i. Yeast infection (3%), hypotension (2.5%), and AKI (2%) were the most common reasons for discontinuation. Using ROC curve analysis, the strongest predictors for AKI were A1C (AUC = 75.8, empirical confidence interval [ECI] 66.5-83.5); baseline SCr (AUC = 72.0 ECI 65.7-78.7); LVEF (AUC = 67.6 ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0 ECI 57.5-74.6). Similarly, the strongest positive predictors for SGLT2i discontinuation were A1C (AUC = 81.1 ECI 74.8-87.2); baseline Scr (AUC = 67.4 ECI 58.7-75.5); LVEF (AUC = 68.7 ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2 ECI 58.2-76.0). Conclusions: A1C was the strongest predictor of AKI and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. SCr, LVEF, and furosemide equivalents also predicted these outcomes.

Devenir des couples demandeurs après leur inscription en don d’ovocytes

ObjectivesMany studies have investigated the causes of discontinuation during intraconjugal medically assisted procreation. However, there are currently very few data justifying the causes of discontinuation during the oocyte donation program. The main objective of this study is to determine the causes of discontinuation in oocyte donation and their respective frequency, excluding live births by oocyte donation in our center. MethodsThis is an observational, retrospective, single-center study focused on receiving or requesting couples who stopped their oocyte donation program between January 1, 2005 and April 29, 2021. A total of 390 couples were included in the study. ResultsOf the 390 couples included, 306 couples or nearly 80%, left our oocyte donation program without obtaining a live birth through this method. The three most frequent reasons for discontinuation were: failure of several oocyte donations (18%), desire of the couples to voluntarily discontinue their care (15%) and separation (14%). Finally, 84 couples obtained at least one live birth by oocyte donation in our center. In addition, 38 women conceived spontaneously and 33 couples benefited from an oocyte donation abroad. ConclusionsThe most common reason for discontinuation in oocyte donation program, excluding live births by oocyte donation in our center, is failure after several oocyte donations. However, 40% of the couples in the study obtained at least one live birth.

Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial

Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m2 every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC. In this phase 3, open-label, randomised study, adult patients aged 18 years or older with SCLC who relapsed after platinum-based chemotherapy were recruited from 135 hospitals across North America, South America, Europe, and the Middle East. Patients were randomly assigned (1:1) centrally by dynamic allocation to intravenous lurbinectedin 2·0 mg/m2 plus doxorubicin 40·0 mg/m2 administered on day 1 of 21-day cycles or physician's choice of control therapy (intravenous topotecan 1·5 mg/m2 on days 1-5 of 21-day cycles; or intravenous cyclophosphamide 1000 mg/m2, doxorubicin 45·0 mg/m2, and vincristine 2·0 mg on day 1 of 21-day cycles [CAV]) administered until disease progression or unacceptable toxicity. Primary granulocyte-colony stimulating factor prophylaxis was mandatory in both treatment groups. Neither patients nor clinicians were masked to treatment allocation, but the independent review committee, which assessed outcomes, was masked to patients' treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02566993, and with EudraCT, 2015-001641-89, and is complete. Between Aug 30, 2016, and Aug 20, 2018, 613 patients were randomly assigned to lurbinectedin plus doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179) and comprised the intention-to-treat population; safety endpoints were assessed in patients who had received any partial or complete study treatment infusions (lurbinectedin plus doxorubicin, n=303; control, n=289). After a median follow-up of 24·1 months (95% CI 21·7-26·3), 303 patients in the lurbinectedin plus doxorubicin group and 289 patients in the control group had discontinued study treatment; progressive disease was the most common reason for discontinuation (213 [70%] patients in the lurbinectedin plus doxorubicin group vs 152 [53%] in the control group). Median overall survival was 8·6 months (95% CI 7·1-9·4) in the lurbinectedin plus doxorubicin group versus 7·6 months (6·6-8·2) in the control group (stratified log-rank p=0·90; hazard ratio 0·97 [95% CI 0·82-1·15], p=0·70). 12 patients died because of treatment-related adverse events: two (<1%) of 303 in the lurbinectedin plus doxorubicin group and ten (3%) of 289 in the control group. 296 (98%) of 303 patients in the lurbinectedin plus doxorubicin group had treatment-emergent adverse events compared with 284 (98%) of 289 patients in the control group; treatment-related adverse events occurred in 268 (88%) patients in the lurbinectedin plus doxorubicin group and 266 (92%) patients in the control group. Grade 3 or worse haematological adverse events were less frequent in the lurbinectedin plus doxorubicin group than the control group (anaemia, 57 [19%] of 302 patients in the lurbinectedin plus doxorubicin group vs 110 [38%] of 288 in the control group; neutropenia, 112 [37%] vs 200 [69%]; thrombocytopenia, 42 [14%] vs 90 [31%]). The frequency of treatment-related adverse events leading to treatment discontinuation was lower in the lurbinectedin plus doxorubicin group than in the control group (26 [9%] of 303 patients in the lurbinectedin plus doxorubicin group vs 47 [16%] of 289 in the control group). Combination therapy with lurbinectedin plus doxorubicin did not improve overall survival versus control in patients with relapsed SCLC. However, lurbinectedin plus doxorubicin showed a favourable haematological safety profile compared with control. PharmaMar.

CML-395 Efficacy and Safety Results From ASCEMBL, a Phase III Study of Asciminib vs. Bosutinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) After ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): Week 96 Update

Asciminib is the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, among patients with CML-CP after ≥2 prior TKIs, asciminib resulted in improved major molecular response (MMR, 25.5% vs. 13.2%) at week 24 and fewer grade ≥3 adverse events (AEs) or AEs leading to treatment discontinuations compared with bosutinib. After a median follow-up of 2.3 years, we report updated efficacy and safety results (data cutoff: October 6, 2021). To compare the MMR rate at week 96 with asciminib vs. bosutinib. A phase III, multicenter, open-label study of adults with CML-CP after ≥2 prior TKIs randomized 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily and stratified by baseline major cytogenetic response (MCyR). In total, 233 patients were randomized to receive asciminib (n=157) or bosutinib (n=76). At data cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) patients, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) patients, respectively. The key secondary objective was met; MMR rate at week 96 was higher with asciminib (37.6%) than with bosutinib (15.8%). The difference after adjusting for MCyR was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). At week 96, more patients receiving asciminib than bosutinib had BCR::ABL1IS ≤1% (45.1% vs. 19.4%). Responses were durable, with a probabilities (95% CI) of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 weeks of 96.7% (87.4%-99.2%) and 94.6% (86.2%-97.9%), respectively, with asciminib and 92.9% (59.1%-99.0%) and 95.0% (69.5%-99.3%), respectively, with bosutinib. Median time to treatment failure was 24 months with asciminib and 6 months with bosutinib. Asciminib had longer duration of exposure (103.1 vs. 30.5 weeks) but fewer AEs leading to treatment discontinuation (7.7% vs. 26.3%) than bosutinib. After >2 years of follow-up, asciminib demonstrated durable responses by continuing to show superior efficacy and better safety/tolerability vs. bosutinib. MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96. These results support the use of asciminib as a new CML therapy.

34574 Systemic medication treatment patterns in adults with atopic dermatitis (AD): Results from the European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD)

Introduction: EUROSTAD (OBS14620) is an observational study of up to 60 months to characterize AD treatment in a real-world setting. Here, we describe systemic treatment-patterns in patients enrolled in EUROSTAD. Methods: Individuals with AD, ≥18 years old and eligible for systemic treatment, were enrolled. Initial study period was 18 months but was amended to 60 months. Treatment was prescribed by study investigators as per clinical practice. Follow-up population is defined as all patients who have completed ≥1 follow-up visit. Reported data is descriptive from the full-analysis set at 24 months. Results: 308 patients were enrolled (mean AD duration: 25.4 years). Most patients reported ≥1 systemic medication use at enrollment (92.5%). During follow-up (n = 295) most patients reported using either one (56.3%) or >1 (41.4%) systemic medication. Cyclosporin, dupilumab, corticosteroids and methotrexate were the most common systemic therapies. Most common reasons reported for treatment initiation were maintenance and exacerbation treatment (both 79.7%), while well-controlled disease (59.7%) and lack of efficacy (38.1%) were the most common reasons for discontinuation. Median duration of systemic treatment was between 1.1-13 months for the most common therapies (corticosteroids, 1.1 months (95% CI 1.0-1.5); cyclosporin, 5.4 months (4.2-6.6), methotrexate, 13.0 months [8.9-16.9]); median duration of dupilumab treatment was not reached because >50% of patients were still on dupilumab at 24 months. Conclusion: AD therapy was started for exacerbation or maintenance treatment and discontinued mainly due to lack of efficacy or well-controlled disease. Patients who initiated dupilumab were more likely to remain on dupilumab compared with other systemic therapies.

Discontinuation of Immune Checkpoint Inhibitor and Survival in Patients With Non-small-cell Lung Cancer Without a Driver Gene Mutation.

Patients with non-small-cell lung cancer treated with immune checkpoint inhibitors (ICI) might be forced to discontinue treatment for various reasons. We conducted a retrospective study to evaluate the impact of discontinuation of ICI treatment on patient prognosis. We performed a retrospective study that reviewed the medical charts of 86 patients treated with ICI monotherapy and 34 patients treated with a combination of ICI and chemotherapy during the period from February 2016 to February 2022 at our two hospitals. 'Discontinuation' was defined as a cessation of ICI treatment for more than two cycles for any reason. The two most common reasons for discontinuation were immune-related adverse events and at the request of the patient. Nineteen patients who had discontinued ICI, resumed ICI or another therapy. Discontinuation of ICI treatment was a favorable factor in overall survival in 84 patients with ICI monotherapy as well as in 34 patients treated with chemotherapy combined with ICI. This analysis found discontinuation of ICI treatment did not adversely affect prognosis. This suggests that when treating patients with non-small-cell lung cancer with ICI, chest physicians should respond flexibly, and, with careful monitoring, consider discontinuation of ICI.

Thrombopoietin receptor agonist discontinuation rates and reasons among patients with immune thrombocytopenia: a study of administrative claims linked with medical chart review.

Administrative claims provide a rich data source for retrospective studies of real-world clinical practice, yet some important data may be inconsistent or unavailable. This study explored factors influencing discontinuation of thrombopoietin receptor agonists (TPO-RAs) among patients with immune thrombocytopenia (ITP), by adding medical chart abstraction for additional details. Adult (≥ 18years) patients with continuous commercial or Medicare Advantage with Part D health insurance coverage were included. Inclusion criteria were ≥ 1 claim for eltrombopag or romiplostim and ≥ 2 diagnoses of ITP between December 31, 2017, and January 1, 2020. Providers were asked to provide access to medical charts for abstraction. The analyses included only patients who discontinued TPO-RA and described patient characteristics, treatment patterns, platelet values, and reasons for discontinuation. Among 207 ITP patients treated with a TPO-RA, 137 (66%) discontinued treatment during the observation period. The mean TPO-RA treatment duration was 185days. Mean platelet count at the time of discontinuation was 197 × 109/L. The most common reason for discontinuation was improvement of the patient's condition (42%). Other reasons included worsening of ITP/lack of response (12%), adverse events (12%), and cost-related or social reasons (23%). No reason was reported for 10%. Notably 26% of patients who discontinued remained off all ITP therapy for the remainder of the study, with a mean treatment-free period of 262days. These results emphasize that some patients with ITP are able to discontinue TPO-RA therapy and achieve durable treatment-free periods.

S155: EFFICACY AND SAFETY RESULTS FROM ASCEMBL, A PHASE 3 STUDY OF ASCIMINIB VS BOSUTINIB IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE AFTER ≥2 PRIOR TYROSINE KINASE INHIBITORS: WK 96 UPDATE

Background: Asciminib is the 1st BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, asciminib had superior efficacy and better safety/tolerability vs bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs). Major molecular response (MMR) rate at wk 24 was 25.5% on asciminib vs 13.2% on BOS; the difference in MMR rates after adjusting for baseline major cytogenetic response (MCyR) was 12.2% (95% CI, 2.19%-22.30%; 2-sided P=.029). Fewer grade ≥3 adverse events (AEs) and AEs leading to treatment discontinuation occurred on asciminib vs BOS. After a median follow-up of 2.3 years (16.5 months’ additional follow-up since the primary analysis), we report updated efficacy and safety results (cutoff: October 6, 2021). Aims: The key secondary objective was to compare MMR rate at wk 96 on asciminib vs BOS. Methods: Eligible pts provided informed consent, were adults with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 European LeukemiaNet recommendations. They were randomized 2:1 to asciminib 40 mg twice daily or BOS 500 mg once daily, stratified by baseline MCyR status (Ph+ metaphases ≤35%). Results: 233 pts were randomized to asciminib (n=157) or BOS (n=76). At cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) pts, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) pts, respectively. MMR rate at wk 96 (per ITT) was 37.6% on asciminib and 15.8% on BOS, meeting the key secondary objective. The difference after adjusting for baseline MCyR was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). Preplanned subgroup analyses showed that MMR rate at wk 96 was consistently higher with asciminib than BOS in all demographic and prognostic subgroups, including all prior lines of TKI therapy, and regardless of the reason for discontinuation of the last TKI (Figure). At wk 96, more pts on asciminib than BOS had BCR::ABL1IS ≤1% (45.1% vs 19.4%) (Table). Responses were durable, with a probability (95% CI) of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 wk of 96.7% (87.4%-99.2%) and 94.6% (86.2%-97.9%), respectively, on asciminib and 92.9% (59.1%-99.0%) and 95.0% (69.5%-99.3%), respectively, on BOS. Median time to treatment failure was 24 months on asciminib and 6 months on BOS. Median duration (range) of exposure was 103.1 (0.1-201.1) wk on asciminib and 30.5 (1.0-188.3) wk on BOS. Despite asciminib’s longer duration of exposure, its safety/tolerability continued to be better than that of BOS (Table). Fewer pts on asciminib than BOS had AEs leading to treatment discontinuation (7.7% vs 26.3%). No new on-treatment deaths were reported since the primary analysis. Most frequent (>10%) grade ≥3 AEs on asciminib vs BOS were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%). Image:Summary/Conclusion: After >2 years of follow-up, asciminib continued to show clinically and statistically significant, superior efficacy and better safety/tolerability vs BOS. Responses were durable, and MMR was more than double on asciminib than BOS. The difference in MMR rates between the 2 arms increased from 12.2% at wk 24 to 21.7% at wk 96. A higher proportion of pts had BCR::ABL1IS ≤1%, a milestone response in later lines that is associated with improved long-term survival. These results further support the use of asciminib as a new CML therapy, with the potential to transform standard of care.

P1138: COPANLISIB + RITUXIMAB VS RITUXIMAB + PLACEBO IN PATIENTS WITH RELAPSED INDOLENT NON-HODGKIN LYMPHOMA (NHL): UPDATED SAFETY AND EFFICACY FROM THE PHASE III CHRONOS-3 TRIAL

Background: The Phase III CHRONOS-3 trial of copanlisib plus rituximab (C+R) vs placebo plus rituximab (P+R) in patients (pts) with indolent NHL (iNHL) showed a significant improvement in progression-free survival (PFS; hazard ratio [HR] 0.52; Matasar et al. Lancet Oncol 2021). At the time of data cut-off (August 31, 2020), 23% of pts were ongoing on treatment in the C+R arm and 43% of pts had discontinued treatment and entered active follow-up; corresponding numbers in the P+R arm were 19% and 17%. Aims: Here we report an updated 1-year follow-up analysis of efficacy and safety for all pts from CHRONOS-3 based on a data cut-off of August 6, 2021. Methods: Eligible pts with iNHL who relapsed after the last R-containing regimen and were progression-free and treatment-free for ≥12 months (mo) after the last R-containing regimen, or for >6 mo if unwilling/unfit to receive chemotherapy, were randomized 2:1 to receive C+R or P+R. All pts provided informed consent. Treatment continued until progression or unacceptable toxicity and was administered i.v. on a 28-day cycle, with C 60 mg/P given on days 1, 8, and 15 and R 375 mg/m2 given on days 1, 8, 15, and 22 of cycle 1 and on day 1 of cycles 3, 5, 7, and 9. Primary endpoint was centrally assessed PFS and secondary efficacy endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), complete response rate (CRR), and treatment-emergent adverse events (TEAEs). Results: 307 pts were randomized to C+R and 151 to P+R. As of the August 2021 cut-off, 46 pts (15.0%) receiving C+R and 16 (10.6%) receiving P+R were ongoing on treatment. The most common reason for discontinuation was adverse events (AEs) unrelated to clinical progression (35.8%) for C+R and radiologic progression (49.7%) for P+R. Similar to the initial disclosure, C+R reduced the risk of progression or death vs P+R by 47%, with median PFS of 22.3 mo (95% confidence interval [CI] 19.4, 30.7) for C+R and 13.8 mo (10.8, 17.5) for P+R (HR 0.53 [95% CI 0.41, 0.70]; p=0.000001). PFS benefit was preserved across all cancer subtypes (HR [95% CI]): follicular lymphoma (n=275; 0.57 [0.41, 0.80]); marginal zone lymphoma (n=95; 0.53 [0.28, 0.99]); small lymphocytic lymphoma (n=50; 0.22 [0.10, 0.49]); lymphoplasmacytic/Waldenström macroglobulinemia (n=38; 0.42 [0.15, 1.16]). Updated ORRs were 80.8% vs 49.7% and CRRs were 34.9% vs 14.6% for C+R vs P+R, respectively. Median OS was not estimable and no significant benefit was seen for C+R over P+R, although the risk of death was reduced (HR 0.86 [95% CI 0.55, 1.32]) vs the August 2020 disclosure (HR 1.07 [0.63, 1.82]). Median DoR was 25.7 mo (17.6, 31.5) for C+R vs 17.3 mo (12.6, 25.3) for P+R; for pts with complete responses, median DoR was 42.3 mo (29.2, not estimable) vs 24.7 mo (10.2, 29.7) (HR 0.46 [0.24, 0.87]). Safety profiles for C+R and P+R were mostly unchanged from the initial disclosure, and the most common treatment-related AEs for pts receiving C+R were hyperglycemia (69.4%), hypertension (49.5%), and diarrhea (33.9%). For C+R, 6 additional pts (2.0%) discontinued C due to an AE, bringing the total to 33.2%. The incidence of grade 3/4 treatment-related TEAEs was generally unchanged with the longer follow-up (2 new grade 4 for C+R; 1 new grade 4 for P+R), with no new grade 5 events. Summary/Conclusion: 1 year after the primary disclosure of CHRONOS-3, C+R continued to demonstrate acceptable safety and superior efficacy with durable complete responses vs P+R in pts with relapsed iNHL. These data support the long-term use of C+R in pts with relapsed iNHL.

Reasons for treatment changes in adults with attention-deficit/hyperactivity disorder: a chart review study

BackgroundAdults with attention-deficit hyperactivity disorder (ADHD) often cycle through multiple treatments for reasons that are not well documented. This study analyzed the reasons underlying treatment changes among adults treated for ADHD in a real-world setting.MethodsData were collected via an online reporting form completed by eligible physicians between October and November 2020. Data for adult patients in the United States who were diagnosed with ADHD and initiated a treatment regimen within 1 to 5 years of chart abstraction were obtained. Reason for a treatment change was described for a randomly selected regimen episode, which spanned from treatment initiation until the earliest among treatment add-on/switch or discontinuation, death, or date of chart abstraction. The overall rate of ADHD/treatment-related complications were also described. Physician satisfaction with current treatment options for adult ADHD and opinions on areas for improvement were assessed.ResultsData on 320 patients were reported by 152 physicians specializing in psychiatry (40.1%), pediatrics (25.0%), family medicine (21.7%), and internal medicine (13.2%). Patients had a mean age of 29.3 years; most were diagnosed with ADHD as adults (57.5%) and within the previous 5 years (56.5%). Selected treatment regimens included stimulants (79.1%), nonstimulants (14.7%), and combination therapy (5.6%) for an average duration of 1.9 years. Among patients with treatment discontinuation (N = 59), the most common reasons for discontinuation were suboptimal symptom management (55.9%), occurrence of ADHD/treatment-related complications (25.4%), and patient attitude/dislike of medication (25.4%). The main reasons for other key treatment changes were inadequate/suboptimal management of symptoms and cost considerations. Over 40% of patients had ≥ 1 documented ADHD/treatment-related complication, irrespective of whether they led to a treatment change. One in 5 physicians (19.8%) were very dissatisfied, moderately dissatisfied, or neither satisfied nor dissatisfied with current treatment options for ADHD in adults; the top 3 suggested improvements were lower risk of abuse (71.7%), longer effect duration (65.1%), and fewer ADHD/treatment-related complications (61.2%).ConclusionsThe top reasons for treatment changes among adults with ADHD are lack of efficacy and ADHD/treatment-related complications, highlighting the importance of developing more effective and safer treatments to alleviate the burden of ADHD.

Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update.

7004 Background: Asciminib is the first BCR::ABL1 inhibitor to specifically target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, asciminib had superior efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. After a median follow-up of 2.3 years (16.5 months’ additional follow-up since primary analysis), we report efficacy and safety results (cutoff: October 6, 2021). Methods: Eligible pts were adults with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 European LeukemiaNet. Pts were randomized 2:1 to asciminib 40 mg twice daily or BOS 500 mg once daily, stratified by major cytogenetic response (MCyR) status (Ph+ metaphases ≤35%) at baseline. The key secondary endpoint was major molecular response (MMR) rate at wk 96. Results: 233 pts were randomized to asciminib (n=157) or BOS (n=76). At cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) pts, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) pts, respectively. MMR rate at wk 96 (per ITT) was higher on asciminib (37.6%) than BOS (15.8%). The difference, adjusting for baseline MCyR, was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). More pts on asciminib than BOS, respectively, had BCR::ABL1IS ≤1% (45.1% vs 19.4%) at wk 96. The probability of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 wk was 96.7% (95% CI, 87.4%-99.2%) and 94.6% (95% CI, 86.2%-97.9%), respectively, on asciminib and 92.9% (95% CI, 59.1%-99.0%) and 95.0% (95% CI, 69.5%-99.3%), respectively, on BOS. Median duration of exposure was 103.1 (range, 0.1-201.1) wk on asciminib and 30.5 (range, 1.0-188.3) wk on BOS. Despite the longer duration of asciminib exposure, safety/tolerability of asciminib continued to be better than that of BOS (Table). No new on-treatment deaths were reported since the primary analysis. Most frequent (&gt;10%) grade ≥3 adverse events (AEs) on asciminib vs BOS were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%). Conclusions: After &gt;2 years of follow-up, asciminib continued to show superior efficacy and better safety/tolerability vs BOS. Responses were durable, with more pts on asciminib in MMR. Additionally, more pts on asciminib had BCR::ABL1IS ≤1%, a milestone response in later lines associated with improved survival. These results continue to support the use of asciminib as a new CML therapy, with the potential to transform standard of care. Clinical trial information: NCT03106779. [Table: see text]

A study of relacorilant in combination with nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma.

4140 Background: Pancreatic cancer remains the third-leading cause of cancer-related death in the US. Average overall survival is only one year, and no standard therapies exist beyond second line. Chemotherapy resistance is one reason for the poor outcomes in pancreatic cancer, which can be caused by, among other factors, excess tumor expression of the glucocorticoid receptor (GR). Nonclinical and clinical data indicate that GR antagonism may enhance or restore chemotherapy sensitivity. Here, we report the interim analysis of RELIANT, a trial evaluating the efficacy and safety of relacorilant, a selective GR modulator, with nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: RELIANT (NCT04329949) was a single-arm, open-label, multicenter study of relacorilant (100 mg QD) + nab-paclitaxel (80 mg/m2 on days 1, 8, and 15 of each 28-day cycle) in patients with histologically confirmed mPDAC. Based on tolerability, relacorilant doses were escalated up to 150 mg. Patients with 2+ prior lines of therapy, including prior gemcitabine- and fluoropyrimidine-based therapy, were enrolled. Planned enrollment was 80 patients. The study included a planned interim analysis after approximately 40 patients had completed 12 weeks of treatment or discontinued study treatment due to disease progression or toxicity. Objective response rate (ORR) by blinded independent central review was the primary endpoint. At the interim analysis, ORR was assessed by the investigator. Results: At the interim analysis, 43 heavily pretreated patients with a median age of 64 years (range: 43–78; 56% male) had been enrolled. 27/43 (63%) patients had received ≥2 prior lines of therapy (range: 2–5), and all but 3 patients had received prior treatment with nab-paclitaxel. Twelve patients (28%) did not have a post-baseline radiographic tumor assessment and were hence not efficacy evaluable. Most common reasons for discontinuation from relacorilant were disease progression (n = 16), adverse event (AE, n = 8), and patient decision (n = 9). Relacorilant + nab-paclitaxel demonstrated antitumor activity with 15/43 (35%) patients showing decreases in target lesion size, 10/43 (23%) achieving disease control for at least 12 weeks, and 17/43 (40%) having decreases in CA 19-9. Of note, one patient has been on study treatment for &gt; 15 months. No confirmed responses by RECIST (CR or PR) were observed, and enrollment was thus stopped after the interim analysis. No new safety signals were identified. The most common AEs were fatigue, nausea, and decreased appetite. Suppression of GR target genes was also observed. Conclusions: Modest antitumor activity of relacorilant + nab-paclitaxel was observed in this heavily pretreated patient population, with a safety profile similar to that observed for relacorilant in other oncology studies. Clinical trial information: NCT04329949.

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.

Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. Data on children aged <18years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16]years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48]months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

POS0666 A MULTINATIONAL, PROSPECTIVE, OBSERVATIONAL STUDY IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING BARICITINIB, TARGETED SYNTHETIC OR BIOLOGIC DISEASE-MODIFYING THERAPIES: 12 MONTH TIME TO DISCONTINUATION, EFFECTIVENESS AND PATIENT REPORTED OUTCOME DATA FROM THE EUROPEAN COHORT

BackgroundBaricitinib (BARI), an oral selective JAK 1/2 inhibitor, is approved for treating adults with moderate to severe active rheumatoid arthritis (RA). RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with RA evaluating time to discontinuation of initial RA treatment for all causes (excluding sustained clinical response) over 24 months (M).ObjectivesThis analysis reports time to discontinuation in the European (France, Germany, Italy, Spain, UK) subgroup, treated with either BARI, biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) or any other targeted synthetic (ts)DMARDs, as well as, the effectiveness of RA treatment, at 12M.MethodsIn the two cohorts, patients were initiated with BARI 2-mg or 4-mg (cohort A), or any bDMARD or tsDMARD (b/tsDMARDs; cohort B). Treatment initiation and changes are at the discretion of the patient or physician. Response rates for remission, low disease activity (LDA), moderate disease activity (MDA) or high disease activity (HDA) were determined using the Clinical Disease Activity Index (CDAI) at 12M. Quality of life using the EQ-5D-5L and patient reported outcome (PRO) measures for pain (pain visual analogue scale; VAS) and physical functioning (Health Assessment Questionnaire Disability Index; HAQ-DI) were also assessed at 12M. This pre-specified interim analysis reports descriptive 12M data using summary statistics, without any inferential testing.ResultsThis analysis involved 1073 adult RA patients with a mean age (standard deviation; SD) of 59.1 (13.2) (cohort A) and 57.0 (13.9) yrs (cohort B), respectively, and a mean disease duration (SD) of 10.0 (9.1) (cohort A) and 8.9 (9.6) yrs (cohort B), respectively. At baseline, 50.9% of patients in cohort A and 31.2% in cohort B initiated treatment as a monotherapy. At 12M, 26.7% of patients in cohort A and 44.1% of patients in cohort B had discontinued treatment. The most common reason for discontinuation in both cohorts was primary non-response. At 12M, 24.1% of patients in cohort A and 16.6% in cohort B achieved CDAI remission (Figure 1). The mean CDAI reduction was -14.5 and -12.0, respectively in cohorts A and B. Mean reductions from baseline in physician global assessment (PhGA) and in patient global assessment (PGA) were -3.4 and -2.5, respectively in cohort A and -3.0 and -2.1, respectively in cohort B. Improvements from baseline in EQ-5D-5L, HAQ-DI, and pain (VAS) were reported in both cohorts at 12M. The mean pain (VAS) reduction from baseline was -24.6 and -19.3 in cohort A and cohort B, respectively.Figure 1.Percentage of pts in cohorts A and B achieving remission and LDA at 12MConclusionThe majority of BARI-treated patients were in remission or had low disease activity and continued treatment at 12M.Table 1.Disease activity and patient reported outcomes at baseline and 12MCohort A BaricitinibCohort B b/tsDMARDsBaseline12MCFBBaseline12MCFBCDAI24.0 (11.7)9.1 (8.2)-14.5 (12.4)23.8 (12.4)10.7 (9.8)-12.0 (12.6)SJC5.2 (4.8)1.3 (2.4)-3.9 (4.8)4.7 (4.9)1.3 (2.8)-3.0 (4.6)TJC7.3 (6.1)2.2 (3.6)-4.7 (6.0)7.8 (6.5)3.0 (4.8)-4.0 (6.1)PhGA5.6 (2.0)2.3 (2.1)-3.4 (2.5)5.5 (2.1)2.5 (2.1)-3.0 (2.6)PGA5.9 (2.3)3.4 (2.5)-2.5 (2.9)5.8 (2.4)3.8 (2.6)-2.1 (3.0)HAQ-DI1.4 (0.7)1.0 (0.8)-0.4 (0.6)1.3 (0.7)1.0 (0.8)-0.3 (0.6)Pain (VAS)59 (23.1)33.2 (26.2)-24.6 (28.7)56.5 (24.3)36.6 (26.5)-19.3 (30.4)EQ-5D-5L0.5 (0.3)0.7 (0.2)0.1 (0.3)0.5 (0.3)0.7 (0.2)0.1 (0.3)Values represent observed mean (SD)b/tsDMARDs; biologic/targeted synthetic disease-modifying anti-rheumatic drugs, CFB; change from baseline, CDAI; clinical disease activity index, SJC; swollen joint count, TJC; tender joint count, P(h)GA; patient (physician) global assessment of disease activity, HAQ-DI; health assessment questionnaire disability index, VAS; visual analogue scale (mm), EQ-5D-5L; European quality of life 5 dimensions 5 levelsDisclosure of InterestsRieke Alten Speakers bureau: Eli Lilly and Company, Pfizer, Galapagos, Consultant of: Eli Lilly and Company, Pfizer, Galapagos, Grant/research support from: Eli Lilly and Company, Pfizer, Galapagos, Gerd Rüdiger Burmester Speakers bureau: Amgen, AbbVie, BMS, Galapagos, Eli Lilly and Company, MSD, Pfizer, Roche, Sanofi, Consultant of: Amgen, AbbVie, BMS, Galapagos, Eli Lilly and Company, MSD, Pfizer, Roche, Sanofi, Marco Matucci Cerinic Speakers bureau: Biogen, Eli Lilly and Company, Grant/research support from: Actelion, Biogen, Novartis, MSD, Andrew Ostor Consultant of: AbbVie, BMS, Roche, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCB, Gilead, Paradigm, Liliana Zaremba-Pechmann: None declared, Marta Herrera Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kathy Gibson Speakers bureau: UCB, Consultant of: Janssen, Novartis, Grant/research support from: Novartis, Employee of: Eli Lilly and Company, Tamas Treuer Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jens Gerwien Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Eli Lilly and Company, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Eli Lilly and Company

Why do men with prostate cancer discontinue active surveillance for definitive treatment? A mixed methods investigation.

ObjectivesTo explore the personal and/or medical reasons patients on active surveillance (AS) have, or consider having, further definitive treatment for their prostate cancer. Research suggests up to 50% of patients on AS will discontinue within 5 years, though reasons for discontinuation from the patient's perspective is under‐explored.MethodsProstate cancer patients who were or had been on AS for at least 6 months were recruited. A questionnaire assessed reasons for receiving/considering definitive treatment and the extent to which reasons were personal or medical. Clinical information was extracted from a state‐level population registry. A subset of participants were interviewed to further explore questionnaire responses.ResultsOne‐hundred and‐three individuals completed the survey; 33 were also interviewed. Fifty‐four survey participants (52%) had discontinued AS for definitive treatment. Common reasons for discontinuation were evidence of disease progression, doctor recommendation, desire to act, and fear of progression. Many participants who considered or had treatment reported weighing medical and personal factors equally in their decision. Interview participants described strongly considering any amount of disease progression and personal factors such as fear of progression, family concerns, and adverse vicarious experiences when deciding whether to pursue treatment.ConclusionBoth medical and personal factors are considered when deciding whether to discontinue AS. Identifying predictors of discontinuation is essential for informing supportive care services to improve AS management.

Interim results from a postmarketing surveillance study of patients with FLT3-mutated relapsed/refractory AML treated with the FLT3 inhibitor gilteritinib in Japan.

ObjectiveGilteritinib received approval for the treatment of FLT3-mutated relapsed or refractory acute myeloid leukemia in Japan in 2018. In accordance with regulatory requirements, we conducted a multicenter, observational surveillance of gilteritinib use in Japan.MethodsPatients were followed for 6 months from gilteritinib treatment initiation. The primary endpoint of the surveillance was incidence of adverse drug reactions related to each element of the safety specification defined in the Japanese Risk Management Plan. This interim analysis presents data collected from 3 December 2018 to 20 September 2020.ResultsAmong 204 patients with case report forms, 107 consented to data publication. Of these 107 patients, 59.8% (n = 64) were male and 58.9% (n = 63) were aged ≥65 years; most received a 120-mg/day initial (80.4%; 86/107) and maximum (74.8%; 80/107) daily dose. The discontinuation rate was 61.7% (66/107); the most common reasons for discontinuation were disease progression (18.7%), transplantation (16.8%) and adverse events (15.0%). The adverse drug reaction rate was 77.6%. The incidences of adverse drug reactions (grade ≥ 3) related to each element of the safety specification were myelosuppression, 44.9% (38.3%); liver function disorder, 24.3% (6.5%); infections, 24.3% (21.5%); prolonged QT interval, 10.3% (2.8%); hemorrhage, 9.3% (6.5%); renal dysfunction, 6.5% (0); hypersensitivity, 5.6% (1.9%); interstitial lung disease, 4.7% (3.7%); cardiac failure/pericarditis/pericardial effusion, 1.9% (0.9%); pancreatitis, 0.9% (0); posterior reversible encephalopathy syndrome, 0.9% (0.9%). The composite complete remission rate was 62.7%; the 6-month overall survival rate was 77.7%.ConclusionGilteritinib treatment for 6 months in Japan was associated with acceptable efficacy and no new safety concerns were observed.

Apremilast Survival and Reasons for Discontinuation in Psoriasis: Five-Year Experience From a Greek Tertiary Care Centre.

IntroductionDrug survival is an indirect measure of efficacy and safety and its post-marketing assessment using real-life data is invaluable.ObjectivesTo investigate the survival of apremilast in a cohort of psoriasis patients treated with apremilast in a Greek hospital.MethodsA retrospective cross-sectional study examined adult psoriasis patients receiving apremilast (March 2016 to January 2021). Primary endpoint was the cumulative survival probability at 52 weeks. Kaplan-Meier analysis was used to calculate survival probability. Cox regression analysis was performed to investigate potential risk factors for apremilast discontinuation.ResultsOne hundred and two patients (29.4% females) with a mean age of 55.9 years (standard deviation 15.21) were included. Sixty-five patients (63.7%) had discontinued treatment by lock date: 19 (18.6%) due to lack of efficacy, 24 (23.5%) due to loss of efficacy, 15 (14.7%) due to adverse reactions, and 7 (6.9%) due to other reasons. Cumulative survival probability at 52 weeks was 52.1%. Median survival time for all reasons for discontinuation was 58 weeks (95% Confidence Interval 40.02, 75.98).ConclusionsApproximately half of patients remained on apremilast after 1 year of treatment. Secondary drug failure was the most common reason for discontinuation.