Main Reason For Discontinuation Research Articles

A single ALS center experience with clinical use of sodium phenylbutyrate-taurursodiol.

The aim of this study was to examine clinical utilization and discontinuation rates of sodium phenylbutyrate-taurursodiol (PB-TURSO) in a single Amyotrophic Lateral Sclerosis (ALS) center. PB-TURSO was approved by the United States Food and Drug Administration (FDA) in September 2022. Prior experience has been limited to clinical trials or expanded access protocols. In this manuscript, we discuss insurance approval rates, patient uptake, and discontinuation of PB-TURSO in a large academic center. Records of patients seen for clinical visits between January 2022 and May 2023 were reviewed. Demographic and clinical characteristics of our clinic population and those initiating PB-TURSO were obtained from our clinical database. A total of 228 patients were seen during the observation period and 122 requested PB-TURSO prescriptions. 77% (94) were approved by insurance. 66% (65) of those who were approved or received free drug chose to start medication. 51% (34) of those who initiated PB-TURSO continued to take it through the end of the observation period. Four patients discontinued due to death during the observation period. Of the 29 patients who survived and discontinued, the main reasons for discontinuation were GI symptoms (17, 58.6%) and taste (8, 29.6%). PB-TURSO was approved by insurance for most patients. The discontinuation rate was high and was driven largely by GI side effects and taste. Future considerations would include deeper examination of demographic trends, patient costs, side effects, and potential benefits in clinical practice.

Incidence and reasons for discontinuation of first-line therapy in patients with multiple myeloma: results from a historical cohort, Brazil 2009-2020.

Multiple myeloma (MM) is an incurable hematological cancer requiring multiple lines of anti-myeloma regimens to promote disease remission and increase patient survival. The study assessed the incidence and reasons for discontinuation of first-line therapy in outpatients who started MM therapy in Belo Horizonte, Brazil from 2009 to 2020. A historical cohort study in which patients were followed from treatment initiation until discontinuation of first-line therapy. Discontinuation of first-line therapy was characterized as (i) discontinuation followed by a second-line therapy, and (ii) discontinuation that prevented patients from receiving a subsequent line of treatment. Non-parametric competing risk analysis with a 95% confidence interval estimated the cumulative incidences of discontinuation followed by a second-line therapy. The probability of discontinuation was compared according to selected variables using the Gray's test at a significance level of 5%. Approximately half of the participants (n = 260) were female and younger than 65 years. Discontinuation of first-line therapy followed by a second-line therapy accounted for 50.4% of the patients and occurred up to 30th month. The main reason for discontinuation not qualifying patients for receiving second-line therapy was to achieve a response to treatment. The maximum times for discontinuation not followed by a second-line therapy ranged from 12 to 20 months due to deaths or response to treatment. The probability of receiving second-line therapy was higher among patients initiating therapy in 2009-2014 and those not undergoing transplantation. In conclusion, discontinuation of first-line therapy followed by second-line treatment occurred as likely as the discontinuation not followed by a subsequent line.

Switching to Doravirine in cART-Experienced Patients: An Effective and Highly Tolerated Option With Substantial Cost Savings.

Doravirine is a non-nucleoside reverse transcriptase inhibitor with demonstrated efficacy as a third agent in treatment-naive and treatment-experienced people living with HIV (PLWH) in registration studies. However, limited real-world data are available. By searching electronic health care records, PLWH using doravirine-based regimens were selected with at least 1 year of follow-up after their first prescription. All stable PLWH who were switched to a doravirine-based regimen were included in the analysis. The primary outcome was the durability of a doravirine-based regimen 1 year after prescription. Reasons for stopping were also collected. Secondary outcomes for PLWH continuing a doravirine-based regimen after 1 year were routine laboratory assessment, body mass index, and differences in medication costs compared with their previous cART. A total of 687 patients (92% men) were included from September 2019 to August 2022: 97.7% switched to doravirine/tenofovir/lamivudine (DOR/TDF/3TC). After 1 year, 94/687 (13.6%) PLWH stopped this therapy. The main reason for discontinuation was patient-reported adverse events in 70/687 (10.2%). Medical reasons for discontinuation included increased alanine tranaminase levels in 6/687 (0.9%), decreased estimated glomerular filtration rate in 3/687 (0.4%), and precautions after diagnosis of osteoporosis in 2/687 (0.3%) patients. Virologic failure occurred in 4/687 cases (0.6%), and 1 case demonstrated resistance mutations. The secondary outcomes demonstrated a statistically significant increase in alanine tranaminase levels and decrease in LDL-c levels. The switch to a doravirine-based regimen in the Netherlands reduced medication costs by 27%. This study demonstrated that switching to a doravirine-based regimen, mostly DOR/TDF/3TC, was highly effective and generally well tolerated, with substantial cost savings.

Long-term retention rates of anti-tumour necrosis factor and anti-interleukin-17 antibodies for patients with psoriatic arthritis

ABSTRACT Objective While biologics have been used for the patients with psoriatic arthritis, there remains to be unknown concerning long-term retention rates. This study aims to present real-world data about long-term retention rates of biologics for the patients with psoriatic arthritis, and to undertake an analysis of the contributing factors. Methods We examined retention rates and the reasons for discontinuation for biologics (adalimumab, certolizumab pegol, secukinumab, and ixekizumab) in 146 prescriptions (of which, 109 prescriptions were as naive) at our hospital since March 2010. Results Throughout the entire course of the study, the 10-year retention rates were approximately 70% for adalimumab, 50% for ixekizumab, and 40% for secukinumab. When evaluating retention rates in the biologic-naïve subgroups, the 10-year retention rates were all approximately 70%. Regarding certolizumab pegol, the 3-year retention rate was approximately 75%. For adalimumab, a higher degree of arthritis at the initiation of treatment was found to correlate with an increased likelihood of secondary inefficacy. The main reason for discontinuation was secondary inefficacy, except for ixekizumab. Conclusions Each biologic exhibited a favourable long-term retention rate. The main reason for discontinuation was secondary inefficacy. Regarding adalimumab, secondary inefficacy was linked to the extent of arthritis upon treatment initiation.

Mezigdomide (MEZI) Plus Dexamethasone (DEX) and Daratumumab (DARA) or Elotuzumab (ELO) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the CC-92480-MM-002 Trial

Introduction : MEZI is a novel oral cereblon E3 ligase modulator (CELMoD ™) with enhanced tumoricidal and immune-modulatory effects compared with immunomodulatory drugs (IMiDs ®). In preclinical studies, MEZI showed synergy with anti-myeloma drugs including DEX, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (mAbs), and is being assessed in the phase 1/2 CC-92480-MM-002 (NCT03989414) trial with different treatment combinations in RRMM. Here we report the preliminary efficacy and safety of MEZI, DARA, and DEX (MeziDd) over 3 dosing schedules, as well as MEZI, ELO and DEX (MeziEd), in pts with RRMM. Methods : Eligible pts had: RRMM, received 2-4 prior lines of therapy, a minimal response or better to ≥ 1 prior regimen, and disease progression during or after their last therapy. In the MeziDd cohort, oral MEZI was given at escalating doses on days (D) 1-21 per 28-D cycle (C) (subcohort B1); on D1-14 per 21-D cycle from C1-8 and D1-21 per 28-D cycle ≥ C9 (subcohort B2); or on D1-7 and D15-21 per 28-D cycle from C1-6 and D1-21 per 28-D cycle ≥ C7 (subcohort B3). Intravenous (IV; 16 mg/kg) or subcutaneous (1800 mg) DARA was given weekly (C1-2), then biweekly (C3-6), and monthly (≥ C7) for subcohorts B1 and B3, and weekly (C1-3) then on D1 of each 21-D (C4-8) or 28-D (≥ C9) cycle for subcohort B2; with weekly oral/IV DEX (40 mg; 20 mg > 75 y or body mass index < 18.5 kg/m 2). In the MeziEd cohort, oral MEZI was given at escalating doses on D1-21 per 28-D cycle, with weekly (C1-2; 10 mg/kg) then monthly (≥ C3; 20 mg/kg) IV ELO, and oral/IV DEX on ELO dosing days (36 mg; 16 mg > 75 y) plus on D8, 15, and 22 of ≥ C3 (40 mg; 20 mg > 75 y). Thromboembolism (TE) prophylaxis was given within 48 hours of C1D1 and until 48 hours after last MEZI dose. Primary objectives were to determine the recommended dose and regimen and to assess safety and preliminary efficacy as overall response rate (ORR). Results : As of the May 25, 2023 data cut, 57 pts were enrolled and had received MeziDd (B1: n = 23; B2: n = 16; B3: n = 18) at the 0.3 mg or 0.6 mg dose. Median age was 67 (range, 45-83) y, median time since initial diagnosis was 8.2 (1.0-15.8) y, and median number of prior regimens was 2 (2-5). Prior therapies included stem cell transplantation (15.8%), IMiD agents (100%), PIs (98.2%), and anti-CD38 mAbs (8.8%); 82.5% of pts were refractory to IMiD agents and 61.4% to PIs. Extramedullary plasmacytomas were present in 4 (7.0%) pts. Forty-five of 57 (78.9%) pts continued treatment; the main reason for discontinuation was progressive disease (5 pts; 8.8%). In the safety population (n = 56), ORR was 75.0% overall, with 2 (3.6%) stringent complete responses, 8 (14.3%) complete responses, 16 (28.6%) very good partial responses, and 16 (28.6%) partial responses (Figure). Duration of response and progression-free survival data were not yet mature. Grade (Gr) 3/4 treatment-emergent adverse events (TEAEs) occurred in 43/56 (76.8%) pts and were mostly hematologic (Table). Gr 3/4 neutropenia occurred in 30 (53.6%) pts; Gr 3/4 thrombocytopenia occurred in 4 (7.1%) pts (3/4 pts were in subcohort B1-0.6 mg) and was not associated with bleeding. Gr 3/4 infections occurred in 11 (19.6%) pts and proved manageable in all cases (Table). Non-hematologic Gr 3/4 TEAEs were low. No Gr 3/4 TE or peripheral neuropathy was observed. MEZI dose reductions were needed for 7 (30.4%) pts in subcohort B1 (1 at 0.3 mg, 6 at 0.6 mg) and 1 (5.6%) pt in subcohort B3 (at 0.6 mg). In the evaluable population (n = 35), 5 (14.3%) pts had ≥ 1 dose-limiting toxicity. The maximum tolerated dose was not reached. MeziDd had pharmacodynamically active immune stimulation in T and NK cells in all 3 schedules and both doses. Twenty pts received MeziEd at 0.3 mg (n = 11) or 0.6 mg (n = 9); median prior lines of therapy was 3 (2-4) and 3 (2-5), and most pts (72.7% and 100%) had prior anti-CD38 mAb exposure. ORRs were 36% and 56%, respectively. The safety profile was consistent with known TEAEs and was generally well tolerated, although 2 Gr 3 pulmonary embolisms occurred. Conclusions : MeziDd showed promising efficacy and a manageable safety profile in pts with RRMM and 2-4 prior lines of therapy, as did MeziEd in pts with prior anti-CD38 mAb therapy. The immune activity of MEZI was consistent with previous preclinical reports. Improved safety and efficacy may be achieved by schedule and dose adjustments. These results support further evaluation of MEZI plus anti-myeloma mAbs in phase 1/2 and phase 3 studies. Updated results will be presented at the meeting.

Five-year Contraceptive Use of 52-mg Levonorgestrel Releasing Intrauterine System in Young Women, Menstrual Patterns, and New Contraceptive Choice.

To evaluate the continuation rates of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) during the first 5 years of use, reasons for its discontinuation, bleeding patterns, and new contraceptive choice after the 5th year, in adolescents and young women. The present study was a 5-year prospective cohort conducted in a Family Planning Service of a tertiary hospital in Brazil. We selected 100 healthy women between 15 and 24 years old who used 52-mg LNG-IUS for contraception. The clinical follow-up of these women took place from June 2017 to December 2022. The study evaluated the continuation rates of the method, reasons for its discontinuation, bleeding patterns, and new contraceptive choice after the 5th year. Continuous data were reported as mean ± standard deviation (SD) and range (minimum-maximum). Categorical variables were described as percentages. The continuation rates of LNG-IUS were 89.1% (82/92), 82.9% (72/87), 75.3% (64/85), 70.5% (60/85), and 64.2% (54/84) in the 1st, 2nd, 3rd, 4th, and 5th years of use, respectively. The main reason for discontinuation was acne (11/30). Amenorrhea rates were 50, 54.1, 39, 35.7, and 51.8% at 12, 24, 36, 48, and 60 months, respectively. All patients who completed the study and needed contraception after the 5th year opted for long-acting contraceptive methods (LARC). The LNG-IUS showed high continuation rates in adolescents and young women in the first 5 years of use. Most patients who completed the study chose a LARC method after the 5th year.

Generation-Dependent Retention Rates and Reasons for Discontinuation of Molecular Targeted Therapies in Patients with Rheumatoid Arthritis: From FIRST Registry.

The study aimed to optimize medical care for elderly patients with rheumatoid arthritis (RA) by examining the 3-year continuation rate of different molecular targeted therapies across age groups in Japan, which has a significant elderly population. The study included patients with RA who started molecular targeted therapies between 2013 and 2019 and divided them into three age groups. The primary outcome was to assess the 3-year continuation rate of each drug and analyze reasons for treatment discontinuation using inverse probability of treatment weighting. Among 2292 patients analyzed, tumor necrosis factor (TNF) inhibitors were most commonly used in those younger than 65years of age (43.5%), while Janus kinase (JAK) inhibitors were also utilized (17.1%). In contrast, JAK inhibitors were less frequently used in patients aged 75years and older (7.8%), with cytotoxic Tlymphocyte antigen4 immunoglobulin fusion proteins (CTLA4-Ig) being the most common (39.2%). JAK inhibitors and anti-interleukin-6 receptor (IL-6R) antibodies had higher continuation rates than other drugs in patients under 65years (p < 0.001). For those aged 65-74years, JAK inhibitors and CTLA4-Ig had higher continuation rates (p < 0.001), while among those aged 75years and older, CTLA4-Ig and IL-6R antibodies had higher continuation rates (p < 0.001). Inadequate efficacy was the main reason for discontinuation in all age groups, while infection leading to discontinuation increased with age. The study highlights the need to consider different age groups separately in elderly RA care. Among patients aged 75years and older, abatacept and anti-IL-6R antibodies showed the highest continuation rates, suggesting their potential suitability and efficacy for this specific age cohort.

Impact of Baricitinib on Patients' Quality of Life after One Year of Treatment for Atopic Dermatitis in Real-World Practice: Results of the Observatory of Chronic Inflammatory Skin Diseases Registry.

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients' lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patient-reported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well.

Treating acute exacerbations of COPD with Chinese herbal medicine to aid antibiotic use reduction (Excalibur): a randomised double-blind, placebo-controlled feasibility trial.

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine "Shufeng Jiedu" (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD. Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care. Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis. Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from "rescue packs" before seeing their GP, and workforce challenges in primary care. Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients' "rescue packs" and delegating recruitment to a central trials team. Clinical Trial Registration: Identifier, ISRCTN26614726.

Two-Drug Regimen Containing Darunavir: Metabolic Evaluation of an Old Dual Therapy.

Regimens containing darunavir are one of the first one with two drugs that demonstrated good efficacy as a simplification strategy. We wanted to describe the characteristics of patients followed in our center on a dual therapy regimen containing darunavir evaluating the metabolic aspects during follow-ups. We collected data from 208 patients switching to lamivudine plus darunavir with either ritonavir or cobicistat between 2010 and 2019. In all patients we found an increase in low-density lipoprotein (LDL), with no rising in creatinine, total cholesterol, or triglycerides. Twenty-five patients reached 120 weeks of follow-up. In these patients, no significant metabolic changes were described without concomitant treatment with drugs for dyslipidemia. These regimens seem to be more tolerable in metabolic profile compared with the data concerning three-drug therapies, leading only to a slight increase in LDL. The main reason for discontinuation was for a single-tablet therapy. None of the patients started treatment for dyslipidemia.

[Analysis of adherence and determinants of sublingual immunotherapy in patients with Artemisia pollen-induced allergic rhinitis].

Objective:To monitor adherence to specific sublingual immunotherapy （SLIT） in patients with seasonal allergic rhinitis（AR）, analyse factors influencing adherence, and provide research support to effectively improve adherence. Methods:Patients with AR who underwent Artemisia pollen SLIT at the Department of Otolaryngology-Head and Neck Surgery, First Hospital of Shanxi Medical University from May 2021 to April 2022 were retrospectively followed up by telephone to investigate the current status of treatment, count the causes of shedding, and extract relevant information from their medical record data for analysis. Results:Of the 112 patients surveyed, 34 discontinued treatment（30.3%）; patients who experienced adverse reactions and SLIT patients who had been on treatment for more than 6 months showed relatively good adherence（P<0.05）. The main reasons for discontinuation in patients who dropped out were: asymptomatic discomfort during the non-pollen phase and therefore discontinuation of treatment or feeling that treatment was ineffective 9 cases（26.5%）, forced discontinuation due to vaccination or pregnancy, or epidemics 6 cases（17.6%）. Conclusion:Long-term adherence of patients to Artemisia pollen SLIT still needs to be brought to the attention of healthcare professionals, especially in the early stages of treatment when good patient education and good channels of trust and communication between doctors and patients need to be established.

Outcomes among Hispanic metastatic breast cancer patients treated with alpelisib and fulvestrant: Single institution retrospective study.

e18836 Background: PIK3CA mutations are found in up to 40% of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancers (MBC). Alpelisib is an oral PIK3CA inhibitor approved in combination with fulvestrant. However, uptake has been limited due to toxicity concerns, most commonly hyperglycemia. Disparities regarding prevalence of diabetes exist among Hispanics (H). We previously reported the incidence and management of hyperglycemia in H MBC patients (pts) treated with alpelisib and fulvestrant at our institution. We now report outcomes and assess treatment patterns of H MBC pts compared to NH MBC pts. Methods: A retrospective chart review was performed to include pts with HR+ HER2- MBC with a documented PIK3CA mutation (detected by ctDNA or tissue) treated with alpelisib in combination with fulvestrant at Miami Cancer Institute from 2019-2022. Pts were identified using pharmacy records and the COTA real-world database (RWD). Cases were excluded where the start date was unclear, or treatment was given for a diagnosis other than breast cancer. Based on available data in the medical record, pts were categorized as H or NH. Descriptive statistical analysis was done using SAS version 9.4 (SAS Inc., Cary, NC). Results: Of 46 pts identified, 34 were included in the final analysis (17 H and 17 NH). The median age was 67 yrs. Median lines of therapy prior to the use of alpelisib and fulvestrant were 3.0 (3 H and 2 NH; p = 0.26). Almost all pts had prior treatment with a CDK4/6 inhibitor (94.1% H vs 100% NH; p = 0.31). Chemotherapy was the most common therapy used after alpelisib discontinuation (41.2% H vs 47.1% NH; p = 0.63). Disease progression was the main reason for discontinuation (64.7% H vs 70.6% NH; p = 0.32) followed by hyperglycemia (23.5% H vs 5.9% NH; p &gt; 0.05). Even though not statistically significant, the median days on treatment were shorter in H compared to NH (131d H vs 217d NH; p = 0.20). A clinical benefit rate of 35.3% was noted in H compared to 58.8% in NH (p = 0.17). Median survival time post receipt of alpelisib was shorter in H compared with NH (15 mo vs 29 mo; p = 0.06). Conclusions: We observed a trend towards shorter time on treatment and median survival time in H pts with HR+ MBC treated with alpelisib and fulvestrant compared to NH pts. This combination was used as second or third line of therapy, with most pts receiving chemotherapy at the time of progression. There was a trend towards less clinical benefit to alpelisib and fulvestrant in H pts vs NH pts. Given hyperglycemia was the second leading cause of treatment discontinuation among H, we hypothesize efforts to optimize glucose control in H will help maximize benefit to therapy and ultimately impact outcomes. Futher studies are warranted to better understand the different outcomes observed in H patients.

Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study

BackgroundAnti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. MethodsAll patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. ResultsAmong a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1–20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0–59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02–2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30–4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15–0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. ConclusionIn a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

Safety and Efficacy of Continuous Subcutaneous Levodopa/Carbidopa Infusion for Parkinson’s disease: Three-Year Data from the Open-Label BeyoND study (PL4.003)

<h3>Objective:</h3> Evaluate three-year outcomes from the ND0612 BeyoND study. <h3>Background:</h3> ND0612 is in development as a continuous, subcutaneous levodopa/carbidopa delivery system for PD patients experiencing motor fluctuations. One year data showed that ND0612 was safe and well-tolerated and provided a sustained ≥2-hour improvement in daily ‘Good’ ON-time without troublesome dyskinesia and a corresponding reduction in OFF-time through 12 months of treatment. <h3>Design/Methods:</h3> The BeyoND study is an ongoing international, open-label study (NCT02726386) evaluating the long-term safety of ND0612 in PD patients experiencing ≥2 hours daily OFF-time. The primary endpoint was assessed at 12 months followed by an extension (OLE) of up to 108 months. <h3>Results:</h3> Of the 114 patients who continued into the OLE, 94 (82.5%) completed ≥2 years and 76 (66.7%) completed ≥3 years of ND0612 treatment; main reasons for discontinuation were withdrawal of consent in the 2^nd (n=8) and 3^rd (n=5) years, and adverse events (AEs) (n=4 and n=10, respectively). Of those patients who started the OLE, treatment-related AEs were reported by 73.7% of patients in Yr1, decreasing to 36.9% in Yr2 and 39.4% in Yr3. While most patients experienced infusion-site reactions (ISRs), these led to early discontinuation in only 4.4% of patients. The incidence of infusion-site infection decreased from 19.3% in Yr1 to 9.9% in Yr2, and 11.7% in Yr3, while incidence of other ISRs decreased from 60.5% in Y1 to 26.1% in Yr2, and 27.7% in Yr3. Dyskinesia was reported in 3.5% of patients in Yr1, none in Yr2, and 1.1% in Yr3. At Month 36, the mean reduction in OFF-time was −2.81h and the increase in Good ON-time was 2.79h. <h3>Conclusions:</h3> Three-year data from this open-label study support the long-term safety, tolerability, and efficacy of ND0612. For patients who entered the OLE, the high rate of retention supports a favorable benefit-risk ratio of ND0612. <b>Disclosure:</b> Dr. Ellenbogen has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for allergan. Dr. Ellenbogen has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for allergan. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for ipsen. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Liat Adar has received personal compensation for serving as an employee of Neuroderm. Laurence Salin has received personal compensation for serving as an employee of NeuroDerm. Dr. Case has received personal compensation for serving as an employee of NeuroDerm. Tamar Yardeni has received personal compensation for serving as an employee of NeuroDerm. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acorda. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sunovion. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Herantis Pharma. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus (formerly USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AskBio. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Supernus (formerly, USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avion Pharmaceuticals. The institution of Dr. Espay has received research support from NIH. The institution of Dr. Espay has received research support from Michael J Fox Foundation for Parkinson’s Research. Dr. Espay has received intellectual property interests from a discovery or technology relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care.

MP79-06 COMPLIANCE OF DAPOXETINE IN PATIENTS WITH PREMATURE EJACULATION: A 2-YEAR PROSPECTIVE OBSERVATIONAL STUDY

You have accessJournal of UrologyCME1 Apr 2023MP79-06 COMPLIANCE OF DAPOXETINE IN PATIENTS WITH PREMATURE EJACULATION: A 2-YEAR PROSPECTIVE OBSERVATIONAL STUDY Hyun Jun Park Hyun Jun ParkHyun Jun Park More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although dapoxetine is the only oral pharmacological agent approved for the treatment of premature ejaculation (PE), and is very effective, the discontinuation rate is high. We assessed the discontinuation rate in patients with PE, and the reasons for discontinuation, in real-world practice. METHODS: A total of 182 consecutive patients were enrolled. The type of PE, the self-estimated intravaginal ejaculation latency time (IELT), and medical history were evaluated in all patients, who also completed the International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) questionnaire. Visits were scheduled 1, 3, 6, 12, and 24 months after initiation of therapy; we checked treatment status and the reasons for discontinuation in those who did in fact discontinue. We compared the relationships of discontinuation rates with various parameters and the time to discontinuation after treatment commencement. RESULTS: Of all patients, 9.9% continued treatment to 2 years. The cumulative discontinuation rates at 1, 3, 6, 12, and 24 months were 26.4%, 61.6%, 79.1%, 87.3%, and 90.1%, respectively. 79.1% of all patients discontinued treatment within 6 months. After 12 months, however, the discontinuation rate fell sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE was not curable and that dapoxetine was required every time sexual intercourse was contemplated (25%), side effects (11.6%), perceived poor efficacy (9.8%), a search for other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (compared to lifelong PE), with IELT >2 min prior to treatment, on PDE-5 inhibitors, and with IIEF-EF scores <26 tended to discontinue early and thus exhibited high drop-out rates. CONCLUSIONS: The treatment discontinuation rate of dapoxetine was very high. The main reasons for discontinuation were the cost and disappointment that treatment was required every time adequate sexual function was required. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1143 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hyun Jun Park More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract PD8-02: Metformin (MET) for the prevention of Alpelisib (ALP)-related Hyperglycemia (HG) in PIK3CA-mutated, Hormone Receptor-Positive (HR[+]) HER2-Negative (HER2[-]) Advanced Breast Cancer (ABC): The METALLICA study

Abstract Background: HG is an on-target AE of PI3K inhibition, reported in 63.7% (36.6% G≥3) of HR[+]/HER2[-] ABC patients (pts) treated with ALP plus fulvestrant in SOLAR-1. HG was the most frequent adverse event (AE) leading to ALP discontinuation (6.3%). MET reduces systemic insulin resistance and suppress PI3K and Ras signaling. METALLICA is assessing the prophylactic use of MET for prevention of ALP-induced G3-4 HG in PIK3CA-mutated, HR[+]/HER2[-] ABC pts with normal fasting glycemia or prediabetic criteria. Methods: This is an open-label, single-arm, two-cohort, phase 2 trial. Pts aged ≥18 years, ECOG PS of 0–1, and PIK3CA-mutated, HR[+]/HER2[-] ABC, progressing to an aromatase inhibitor (AI)-containing regimen, ≤2 previous endocrine therapy (ET) and ≤1 prior chemotherapy regimens for ABC were eligible. Pts were enrolled into cohorts according to glycemia at baseline: (A) pts with normal fasting glycemia &amp;lt; 100 mg/dL and glycosylated hemoglobin (HbA1c) &amp;lt; 5.7%; (B) pts with prediabetic fasting glycaemia 100–140 mg/dL and/or HbA1c 5.7–6.4%. Pts received oral ALP 300 mg/day, starting from C1D8, in combination with ET; fulvestrant, letrozole, or exemestane as per standard of care; and oral MET 1000 mg/day on days 1-3 and 2000 mg/day thereafter. The primary endpoint was G3-4 HG incidence as per NCI-CTCAE v.4.03 at 2 first cycles of treatment. Assessment of glycemia was performed by rigorous self-monitoring blood glucose and local laboratory confirmation in fasting conditions. Secondary endpoints included objective response (ORR), clinical benefit rate (CBR), duration of response (DoR), progression-free survival (PFS), and safety. Sample size was based on a Simon’s two-stage design in cohorts A (H0: G3-4 HG ≥25%; H1: G3-4 HG ≤10%) and B (H0: G3-4 HG ≥40%; H1: G3-4 HG ≤15%). We planned to attain 80% power at the nominal one-sided α level of 0.05 for each cohort. Results: Between Aug 30, 2020, and Mar 10, 2022, 68 pts were enrolled at 18 sites (48 cohort A, 20 cohort B). Median age was 55 (range, 29–79) years and 58.8% pts had visceral disease and an ECOG PS 0. A total of 66 (97.1%) pts had been previously treated with a CDK4/6i and 13 (19.2%) pts had received chemotherapy for advanced disease. Sixty-three (92.6%) pts received fulvestrant as ET (45 cohort A, 18 cohort B). With a median follow-up of 8 (range, 1.6–14.9) months, 28 (41.2%) pts remain on study treatment. Disease progression was the main reason for discontinuation, reported in 32 (47.1%) pts. The primary endpoint of the study was reached, with 1 (2.1%) pts (95%CI, 0.8–9.5; p &amp;lt; 0.001) in cohort A and 3 (15%) pts (95%CI, 4.5–33; p = 0.012) in cohort B experiencing a G3-4 HG episode over the 2 first cycles of treatment. For patients on fulvestrant, G3-4 HG rates were 1 pts (2.2%) and 3 (16.7%) pts for cohorts A and B, respectively. No ALP discontinuation related to HG was reported during the first 2 treatment cycles. Median PFS in all patients was 7.4 months (95%CI, 6–NA). Among pts with measurable disease, ORR was 14 (36.8%) pts (95%CI, 21.8–54). At the time of this analysis, DoR and CBR were still immature. The most common AEs were diarrhea (67.6%; 13.2% G≥3), nausea (67.6%; 0% G≥3), and fatigue (45.6%; 2.9% G≥3). Serious AEs occurred in 15 (22.1%) pts. The main serious AEs were rash (2.9% G≥3) and vomiting (1.5% G≥3). No additional pts reported G≥3 HG after the first 2 cycles. The dose of ALP was reduced according to the protocol in 19 (27.9%) pts. Eight (11.8%) pts permanently discontinued ALP due to AEs, none of whom related to HG. No treatment-related deaths were reported. Conclusions: Prophylactic use of MET substantially reduced the incidence and severity of ALP-related HG with no additional toxicities and could be a new standard for PIK3CA-mutated, HR[+]/HER2[-] ABC pts receiving ALP plus fulvestrant or other ET. Citation Format: Manuel Ruiz Borrego, Pablo Tolosa, Salvador Blanch, Adela Fernández, Ander Urriticoechea, Isabel Blancas, Cristina Saura, Beatriz Rojas, Begoña Bermejo, Jose Ponce, Maria Gión, Elisenda Llabres, Elena Galve, Juan Fernando Cueva, Ana López, José L Alonso-Romero, Santiago González-Santiago, Eduardo Martínez De Dueñas, Fernando Gomez Peralta, Eva Ciruelos, José Manuel Pérez-García, Antonio Llombart-Cussac, Javier Cortés. Metformin (MET) for the prevention of Alpelisib (ALP)-related Hyperglycemia (HG) in PIK3CA-mutated, Hormone Receptor-Positive (HR[+]) HER2-Negative (HER2[-]) Advanced Breast Cancer (ABC): The METALLICA study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-02.

Efficacy and Tolerance of Thalidomide in Patients With Very Early Onset Inflammatory Bowel Disease.

Few drugs have been studied for patients with very early onset inflammatory bowel disease (VEOIBD). This study aimed to evaluate the efficacy and tolerance of thalidomide in children with VEOIBD compared with children with pediatric-onset IBD (pIBD). A retrospective cohort study with a control group was conducted. Propensity score 1:1 matching was used to identify control subjects. The treatment persistence; the causes of drug withdrawal; the rate of clinical remission and mucosal healing at 1, 2, and 3 years; and adverse events (AEs) were evaluated in children with VEOIBD treated with thalidomide and compared with children with pIBD. Thirty-nine courses of treatment with thalidomide in VEOIBD and pIBD patients were compared. The treatment persistence at 1, 2, and 3 years was 68.2% (95% confidence interval [CI], 50.8%-80.6%), 57.0% (95% CI, 39.6%-71.1%), and 50.9% (95% CI, 33.7%-65.8%) for VEOIBD patients and 81.7% (95% CI, 65.3%-90.9%), 60.0% (95% CI, 41.7%-74.3%) and 33.0% (95% CI, 17.4%-49.5%) for pIBD patients, respectively (P = .12). A significantly higher proportion of VEOIBD patients discontinued therapy due to lack of efficacy (48.2% vs 17.2%; P = .03), while AEs were the main reason for discontinuation in pIBD patients. Clinical remission and mucosal healing rates did not significantly differ between VEOIBD and pIBD patients. A significatively lower number of VEOIBD patients experienced AEs compared with pIBD patients (14 [35.9%] vs 30 [76.9%]; P = .0005). Thalidomide is an effective and tolerated treatment in children with VEOIBD. Discontinuation due to lack of efficacy is more frequent, but AEs are less common than in children with pIBD.

Comparison of Virological Efficacy of DTG/ABC/3TG and B/F/TAF Regimens and Discontinuation Patterns in Persons Living with Advanced HIV in the Era of Rapid ART: A Retrospective Multicenter Cohort Study.

International treatment guidelines recommend the rapid initiation of antiretroviral therapy (ART) with bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) and dolutegravir (DTG)-based regimens for treatment-naïve persons living with HIV (PLWH) irrespective of their disease stage. However, we lack evidence of the virological efficacy, virological failure, and tolerability of coformulated B/F/TAF and DTG/ABC/3TC regimens in persons living with advanced HIV (PLWAH; defined as persons with a CD4+ count of < 200cells/μL or an AIDS-related opportunistic illness [AOI] at or before ART initiation) in the era of rapid ART. This retrospective multicenter study enrolled treatment-naïve PLWAH initiating ART with coformulated DTG/ABC/3TC or B/F/TAF in 2019-2020. Viral suppression at week48 was analyzed using FDA snapshot analysis. Between-regimen differences in time to viral suppression (< 50copies/mL), virological failure, and regimen discontinuation were examined using a Cox proportional hazards model. Analysis was also performed using time to regimen discontinuation due to adverse reactions (ARs) as the outcome. We enrolled 162 patients, including 61.1% on DTG/ABC/3TC and 38.9% on B/F/TAF. At week48 after ART initiation, 73.47% on DTG/ABC/3TC and 85.71% on B/F/TAF achieved viral suppression (P = 0.178). We identified no between-regimen differences in time to viral suppression or virological failure, regardless of pre-ART viral load. Compared with the DTG/ABC/3TC group, regimen discontinuation was less prevalent in the B/F/TAF group (adjusted hazard ratio = 0.23, 95%CI 0.06-0.85, P = 0.027). The main reason for discontinuation in both groups was ARs (61.9% in the DTG/ABC/3TC and 50% in the B/F/TAF, P = 0.877), of which skin manifestations were the most common in both groups (61.5% in the DTG/ABC/3TC and 50% in the B/F/TAF, P = 0.756). DTG/ABC/3TC, same-day ART prescription, and AOI were risk factors for AR or virological failure-related regimen discontinuation. In the real world, the risk of regimen discontinuation was higher in PLWAH on coformulated DTG/ABC/3TC than in those on B/F/TAF, with no difference in viral suppression or virological failure. Given the findings concerning the effect of same-day ART prescription and AOIs on AR or virological failure-related regimen discontinuation, individualized approaches to PLWAH are necessary.

Front-line fludarabine-cyclophosphamide-rituximab (FCR) in 110 patients with chronic lymphocytic leukaemia (CLL): real-life experience with long-term outcomes, toxicities and responses to second-line therapies.

Fludarabine-cyclophosphamide-rituximab (FCR) has been the gold standard front-line treatment for fit CLL patients until novel agent's introduction. Decision between either time-limited FCR or "endless" Bruton's tyrosine kinase inhibitor (BTKi) therapy may be difficult in fit IGHV-mutated-non-TP53 cases. We describe the outcomes after front-line FCR in 110 CLL patients from 5 centres in Catalonia, Spain, over a period of more than 10years. ORR was 96.3% and CR 74.5%. Median second-treatment free survival (TFS1) was 6.2years and median OS was 10.8years. 50 (45.5%) patients required a subsequent therapy. Median third-treatment free survival was better for BTKi than for chemotherapy ± antiCD20 strategies (not reached vs 3.1years, p = 0.003). Only 50 (45.5%) patients completed 6 cycles of FCR, and the main reason for discontinuation was cytopenia 29 (26.4%). 15 (13.6%) patients developed a second cancer, and 5 (4.5%) patients experienced a Richter's transformation (RT). At the end of follow-up, 50 (45.5%) patients remained in CR. Response rates, TFS1, OS, RT, and second cancers did not differ between patients treated with 6 vs 4 cycles of FCR. In conclusion, front-line FCR treatment leads to very long CR in almost half of patients, and BTKi yields excellent outcomes in relapsed patients.

Mezigdomide (CC-92480), a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD), Combined with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Dose-Expansion Phase of the CC-92480-MM-001 Trial

Introduction: Mezigdomide (MEZI), a novel oral CELMoD® agent with enhanced tumoricidal and immune-stimulatory effects compared to immunomodulatory drugs (IMiDs®), induces maximal degradation of Ikaros and Aiolos, leading to increased apoptosis in myeloma cells. Preclinically, MEZI demonstrated potent synergy with DEX, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (mAbs). CC-92480-MM-001 (NCT03374085) is an ongoing phase 1/2 trial evaluating MEZI alone or in combination with DEX in pts with RRMM; in phase 1, the recommended phase 2 dose (RP2D) of MEZI in combination with DEX was selected at 1 mg once daily for 21/28 days (Richardson PG, et al. J Clin Oncol 2020;30[15 suppl]:8500). Here we report results from the dose-expansion cohort of MEZI + DEX in pts with heavily pretreated RRMM. Methods: Eligible pts had: RRMM; ≥ 3 prior lines of therapy; disease progression on or within 60 days of last myeloma therapy; refractoriness to LEN/POM, a PI, a glucocorticoid, and an anti-CD38 mAb. MEZI 1 mg was given orally on days 1-21 of each 28-day cycle, plus weekly DEX (40 mg; 20 mg if > 75 years of age). Primary objective was to determine efficacy by overall response rate (ORR); secondary objectives included safety/tolerability and additional efficacy assessments. Efficacy was also assessed in pts with plasmacytomas and in pts with prior anti-B-cell maturation antigen (BCMA) therapy. Pharmacodynamics was an exploratory objective. Results: As of May 24, 2022, 101 pts had received MEZI + DEX at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years, and 20.8% of pts had ISS stage III at study entry. Plasmacytomas were present in 38.6% of pts and 36/101 pts had high-risk cytogenetics (55/101 pts were not evaluable). Median number of prior regimens was 6 (range 3-15). Prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%) (Table 1). All pts were refractory to last myeloma regimen and triple-class refractory (refractory to an IMiD agent [LEN/POM], a PI, and an anti-CD38 mAb), and 39.6% of pts were refractory to LEN, POM, ≥ 2 PIs, and an anti-CD38 mAb. Median follow-up was 5.8 (range 0.5-19.0) months, with a median number of 4 (1-18) cycles received and 23 (22.8%) pts continued on treatment. The main reason for discontinuation was progressive disease (50.5%). ORR was 39.6%, with 2 (2.0%) stringent complete responses, 3 (3.0%) complete responses, 18 (17.8%) very good partial responses, and 17 (16.8%) partial responses (Table 2). While data are not yet mature, the preliminary median duration of response was 8.3 (95% confidence interval [CI] 5.4-not reached) months and median progression-free survival was 4.6 (95% CI 3.2-6.3) months. ORR was 30.8% in pts with plasmacytomas (N = 39) and 50.0% in pts with prior anti-BCMA therapy (N = 30). Grade (Gr) 3/4 treatment-emergent adverse events (TEAEs) were reported in 90 (89.1%) pts. Most frequent (≥ 20% pts) hematologic Gr 3/4 TEAEs were neutropenia (74.3%, with 14.9% febrile neutropenia), anemia (32.7%), and thrombocytopenia (25.7%). Gr 3/4 infections were observed in 32.7% of pts; Gr 3/4 pneumonia and COVID-19 were present in 9.9% and 5.0% of pts, respectively. The occurrence of other Gr 3/4 non-hematologic TEAEs was generally low, including gastrointestinal disorders (5.9%), fatigue (4.0%), and rash (1.0%). Seventy-two (71.3%) pts and 29 (28.7%) had MEZI dose interruptions and reductions due to TEAEs, respectively; 6 (5.9%) pts discontinued MEZI due to TEAEs, with 1 pt due to hematological TEAEs. MEZI induced potent pharmacodynamic effects in this cohort, including substrate degradation and increases in activated and proliferating T cells in all pts, as well as in pts directly refractory to POM-based therapies demonstrating the mechanism of MEZI action is still functioning in this heavily pretreated population. Conclusions: MEZI + DEX had a manageable safety profile and demonstrated promising efficacy in pts with triple-class refractory RRMM, including pts with prior BCMA-targeted therapies, with an ORR of 40% and 50% respectively. These results support the development of MEZI in pts with MM. MEZI is currently being evaluated in combination with standard therapies in MM as part of a large, ongoing phase 1/2 trial (NCT03989414) and phase 3 trials in combination with PIs are planned. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal