ITT Group Research Articles

Dental Autotransplantation or Immediate Single Implant for the Replacement of a Hopeless Molar: A Comparative Case Series Study.

Dental autotransplantation (ATT) of mature teeth in adult patients has recently been supported by a growing body of evidence. Thus, ATT can be considered as an alternative to single implants for the replacement of a compromised tooth. This case series study aims to provide an initial comparison between ATT (test group) and immediate implant treatment (IIT standard group), in terms of volumetric changes and patient-related outcome measures (PROMs). Thirty-one interventions (29 patients) were grouped into two similar cohorts. Measurements were made on the superimposed STL files before and at least six months after treatment, and PROMs were obtained from a questionnaire in two follow-up checks. Data were analyzed using descriptive and inferential statistics. Adverse events and complications were also recorded. Volume reduction was 3 to 4 times less in the ATT group than in the ITT group (p<0.05). Patients in the ATT group reported higher levels of perceived inflammation than the IIT group (p&#61;0.015), although patients rated satisfaction similarly between the two treatments, above 9 on a scale of 1-10. Although this research should be considered an initial step requiring larger samples and follow-up, it supports the trend of including ATT as an alternative option to IIT in molar replacement.

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis: Results from the ACE-536-MF-001 study.

7016 Background: Many patients (pts) with myelofibrosis (MF) experience anemia resulting from disease or JAK inhibitor therapy. The open-label, phase 2 ACE-536-MF-001 study (NCT03194542) evaluated the safety and efficacy of luspatercept (LUSPA) for the treatment of MF-related anemia. Methods: Eligible pts comprised 4 cohorts based on transfusion dependence (TD, defined as receiving 4–12 red blood cell [RBC] units/84 days [d] immediately up to cycle 1 d 1) and stable ruxolitinib (RUX) treatment; cohort 1: no TD, no RUX; cohort 2: TD, no RUX; cohort 3A: no TD, RUX; cohort 3B: TD, RUX. Pts received subcutaneous LUSPA 1.0 mg/kg (1.33 mg/kg for pts in cohort 3B expansion) with titration up to 1.75 mg/kg in 21-d cycles. Disease response was assessed at d 169 and treatment extended for pts showing clinical benefit; pts were followed for ≥ 3 years (y) post last dose. The primary endpoint was anemia response (defined as 84 consecutive d: ≥ 1.5 g/dL hemoglobin [Hgb] from baseline without transfusion [cohorts 1 and 3A] or RBC transfusion-free [cohorts 2 and 3B]); secondary endpoints included duration of response (DOR), transfusion frequency, change in Hgb level, and symptom response. Results: Of 95 pts in the ITT group, the most common reason for treatment discontinuation was lack of clinical benefit at d 169 (n = 28). Median (range) age was 71.0 (50–89) y. Most (54.7%) pts had primary MF, intermediate-risk 2 disease (75.8%), and &gt; 2 y since initial diagnosis (74.7%). Median prior RUX therapy was 18.1 months (cohorts 3A/3B) and 84.7% of pts had baseline transfusion burden 6–12 units/84 d (cohorts 2/3B). Mean treatment duration was 42.8 weeks. Cohort 3B had the highest anemia response rate with 26.3% (95% CI, 13.4–43.1) of pts transfusion independent during the primary treatment period and 31.6% (95% CI, 17.5–48.7) transfusion independent during the entire treatment period; median (range) DOR was 448 d (85–1582). In cohort 3B: 19 (50.0%) pts had reduced transfusion burden by ≥ 50% during the primary treatment period; 8 (21.1%) pts achieved mean Hgb increase ≥ 1.5 g/dL from baseline throughout the entire treatment period and 6 (15.8%) achieved a mean ≥ 50% reduction in symptom score from baseline. Overall, 47.4% of pts had ≥ 1 treatment-related adverse event (TRAE), most frequently hypertension (17.9%, 5.3% grade ≥ 3); 3.2% of pts had a serious TRAE. One TRAE led to LUSPA discontinuation. Two (2.1%) pts had transformation to acute myeloid leukemia. Nine pts died on treatment from: post-procedural hemorrhage, pneumonia, intracranial hemorrhage, septic shock, ischemic stroke, multiple organ dysfunction syndrome, renal failure, pneumonitis, and myelofibrosis (n = 1 each); no deaths were considered related to the study drug. Conclusions: In pts with MF, the safety profile of LUSPA was consistent with previous studies and efficacy results showed promising improvements in anemia and transfusion burden in all cohorts. Clinical trial information: NCT03194542 .

A phase II trial of risk-enabled therapy after initiating neoadjuvant chemotherapy for bladder cancer (RETAIN).

438 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy or chemoradiation is the standard of care for urothelial carcinoma (UC) patients with MIBC. Both cystectomy and chemoradiation have short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients prospectively for a cystectomy or chemoradiation avoidance algorithm. Methods: We conducted a single-arm, phase II, non-inferiority trial (NCT02710734) to evaluate a risk-adapted approach for MIBC. Patients with cT2-T3N0M0 UC underwent NAC with accelerated MVAC. Pre-NAC TURBT specimens were sequenced (Caris) for mutations in ATM, ERCC2, FANCC or RB1. Patients with ≥ 1 mutations and no clinical evidence of disease by restaging TUR, urine cytology and imaging post-NAC began pre-defined active surveillance (AS). Remaining patients underwent bladder-directed therapy. The primary endpoint was metastasis-free survival (MFS) at 2 years for the entire cohort. The risk-adapted approach would be declared non-inferior to the standard of care if the lower bound of an exact 1-sided 95% CI for MFS was &gt; 64%. The study required 70 patients with a 4.5% type I error and 81.6% power. Results: 71 (ITT) patients were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ECOG PS 0 and 79% cT2. 90% completed 3 cycles of MVAC with 17% grade 3-4 TRAEs. In the ITT population, 33 (46%) had a relevant mutation and 26 (37%) began AS. With a median follow-up of 41 months, 47 patients (66%) are metastasis-free (CI 54%-77%). The 2-year MFS for the ITT patients (primary endpoint) was 72% (lower bound exact 1-sided 95% CI=62%). On post hoc analysis, the 2-year MFS was 65% in the AS group (CI 44%-83%) and 76% (CI 60%-87%) in the remaining patients (P=0.42). In the AS group, 18 patients (69%) had some UC recurrence, 8 had a cystectomy, 2 chemoradiation, and 13 (50%) are metastasis-free with an intact bladder. Of the 10 patients (38%) on AS who developed metastatic disease, 9 recurred with localized disease first. The 2-year OS is 83% (CI 72%-90%) and 89% (CI 68%-96%) in the ITT and AS groups, respectively. Associations between mutation presence and MFS or UC recurrence were not observed. Conclusions: The 72% 2-year MFS rate in this MIBC cohort treated with a risk-adapted approach did not satisfy the pre-specified non-inferiority condition. 38% of AS patients developed metastatic disease, with most patients first recurring locally in the bladder. With a median follow-up of 41 months, although 50% of AS patients have been able to avoid cystectomy without metastatic disease, further refinement of this approach is necessary. Clinical trial information: NCT02710734 .

S179: RANDOMIZED COMPARISON BETWEEN KRD AND KTD INDUCTION, FOLLOWED BY K MAINTENANCE OR OBSERVATION IN TRANSPLANT NON-ELIGIBLE PATIENTS WITH NDMM (AGMT-MM02 TRIAL)

Background: Carfilzomib (K)-based combinations have been established as effective frontline and relapse regimens in pts with multiple myeloma (MM). Aims: In this randomized phase II trial we evaluated the impact of either Revlimid (R) or Thalidomide (T) as combination partner for K and dexamethasone (KRd or KTd) on outcome in pts with newly diagnosed MM (NDMM) not eligible for autologous transplantation (TNE). Further, we evaluated the role of one year K maintenance therapy compared to observation. Methods: One hundred twenty two pts have been enrolled (ITT population). Median age was 75 yrs, ISS stage I/II/III: 29 (23.8%)/48 (39.3%)/45 (36.9%), ECOG stage 0/1: 64 (52.5%) / 58 (47.5%). t(4;14) ± del17p was noted in 15 (16.3%) of 92 pts with results available. Pts were randomized to 9 cycles of KRd or KTd, and 107 pts received at least one full cycle. Carfilzomib (K) was started with 20mg/m2 at d 1 of cycle 1, and was continued with 27mg/m2 for the first 2 cycles (d 1 + 2, 8 + 9, 15 + 16 schedule); followed by K administration at 57mg/m2 once weekly for a 28 d cycle. Thalidomide 100mg/d (50mg in pts >75 yrs of age), d 1-28, or Revlimid 25mg/d (15mg in pts 375 yrs of age) d 1-21. Dexamethasone 40mg (20mg in pts 375 yrs of age) once/week. After induction, pts with 3SD were randomized to K maintenance (d 1 and 15) for 12 cycles or observation. MRD was assessed by NGF with a sensitivity of 10-6 in pts with ≥VGPR. Survival estimates were calculated according to Kaplan-Meier and survival curves were compared with the log-rank test. PFS and OS results presented are given for the ITT population. This trial is registered on clinicaltrials.gov (NCT02891811). Results: Median follow-up was 25.3 mos, 15 pts discontinued therapy within the first cycle due to patient (3) or investigator (1) decision, AE/toxicity (8), death or progressive disease (2) or other reason (1). Overall response rate was 91.3% in the entire group with available data (n=115). Results for sCR, CR, VGPR, PR, and ORR for KRd and KTd were similar between both groups (7.3%/10.0%, 27.3%/33.3%, 38.2%/35.0%, 14.5/16.7%, 87.3%/95.0%, respectively). Minor response was noted in 4 (3.5%), stable disease in 5 (4.3%) and progressive disease in 1 (0.8%) pts. PFS (median 26.9 and 23.5 mos, p=0.832) and OS (not reached vs 52.2 mos, p=0.398) were similar between the KRd and KTd group, respectively. The OS rate at 36 mos was 82% in both groups. MRD testing was performed in 57 pts at time of CR/VGPR. Of those, 43.9%, (20.5% of the ITT group) pts were found to be MRDneg. PFS was significantly longer in MRDneg vs. MRDpos pts (p=0.003). Seventy six pts were randomized to K maintenance therapy or observation. Median PFS was numerically higher in the pts with K maintenance treatment (median 33.0 vs 24.0, p=0.714), but the difference was not statistically significant. Data on OS are not mature yet (only 9 events). Grade 3/4 hematologic AEs were anemia (4.1%), leukopenia (0.8%), thrombocytopenia (7.4%), while non-hematologic grade 3/4 AEs were infection (20.5%), GI-disorders (7.4%), hypertension (7.4%), renal and cardiac impairment/failure (6.6% and 8.2% respectively). Image:Summary/Conclusion: Our data show similar high efficacy of KRd and KTd in elderly NTE NDMM pts, including no difference in ORR (KRd and KTd, 87.3% and 95%, respectively), PFS and OS. Overall survival rate at 3 yrs was 82%. Median PFS was significantly longer in MRDneg pts. PFS was numerically, but not statistically longer in pts on K maintenance vs observation. Treatment was associated with an acceptable tolerance profile.

An on-site community-based model for hepatitis C screening, diagnosis, and treatment among people who inject drugs in Kerman, Iran: The Rostam study.

People who inject drugs (PWID) are at high risk for hepatitis C virus (HCV) infection and its complications in many countries, including Iran. This pilot study aimed to evaluate the effect of a community-based HCV model of care on HCV testing and treatment initiation among PWID in Kerman, Iran. This study is part of the Rostam study and is a non-randomized trial evaluating the effect of on-site HCV- antibody rapid testing, venipuncture for HCV RNA testing, and treatment eligibility assessment on HCV testing and treatment initiation among PWID. Recruitment, interviews, and HCV screening, diagnosis, and treatment were all conducted at a community-based drop-in center (DIC) serving PWID clients. A total of 171 PWID (median age of 39 years and 89.5% male) were recruited between July 2018 and May 2019. Of 62 individuals who were HCV antibody positive, 47 (75.8%) were HCV RNA positive. Of RNA-positive individuals, 36 (76.6%) returned for treatment eligibility assessment. Of all the 36 participants eligible for treatment, 34 (94.4%) initiated HCV antiviral therapy. A sustained virologic response at 12 weeks post-treatment was 76.5% (26/34) in the intention-to-treat (ITT group) analysis and 100% (23/23) in the per-protocol (PP group) analysis. Our integrated on-site community-based HCV care model within a DIC setting suggested that HCV care including HCV testing and treatment uptake can be successfully delivered outside of hospitals or specialized clinics; a model which is more likely to reach PWID and can provide significant progress towards HCV elimination among this population.

Cognitive Remediation Therapy for Participants with Late Life Schizophrenia

<h3>Introduction</h3> Cognitive deficits strongly predict function in schizophrenia, including in late life. Cognitive remediation (CR) improves cognition in schizophrenia, however literature in late-life schizophrenia (LLS) is sparse. Anticholinergic medication burden (ACB) compounds age-related cognitive declines in late-life schizophrenia (LLS). This study examined the effect of CR on cognitive performance in patients with LLS. We also assessed CR tolerability, the interaction between ACB and CR on cognition. <h3>Methods</h3> We adapted CR from our pilot study to a larger group. CR was provided over 12, twice-weekly, therapist-guided group sessions. Computerized drill-and-practice exercise difficulty levels were adjusted automatically based on performance. Participants were assessed at baseline and at study completion using clinical and cognitive measures. <h3>Results</h3> Thirty-four participants were enrolled and 20 (mean (SD) age: 66.0 [5.8]) completed 92.3% (22.14 [1.98]) all CR sessions; the ITT group (N=34) attended 72.9% (17.50 [7.23]) sessions. Global cognition did not improve (completers: p=0.80, ITT: p=0.86) with negligible effect size (completers: d=0.08; ITT d=0.04). There was no significant improvement in executive function (completers: p=0.16; ITT: p=0.33). Medication ACB was inversely associated with total MoCA score, accounting for 8.9% of the variance in final MoCA score (p=0.02). <h3>Conclusions</h3> Overall, CR was well tolerated but did not improve global cognition or executive functioning in this outpatient sample with LLS. A higher ACB was associated with greater cognitive impairment and a poorer response to CR. Future studies need to better characterize potential variables serving to limit the response to CR, including the number and frequency of CR sessions and the role of ACB. <h3>This research was funded by</h3> Funding for this project was provided by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario

The effectiveness of eradication therapy of the 1st line of Helicobacter pylori infection in patients with type 2 diabetes mellitus

Evaluation of the efficacy and safety of eradication therapy of infection Helicobacter pylori in patients with H. pylori- associated pathology of the upper gastrointestinal tract and concomitant type 2 diabetes mellitus (DM). The prospective randomized study involving 180 patients (87 men and 93 women) with H. pylori- associated pathology of the upper gastrointestinal tract was carried out. The patients were divided into four groups of 45 people: 1 patients without diabetes who received the classic triple eradication therapy; 2 patients with type 2 DM who received the classic triple eradication therapy; 3 patients without DM who underwent quadrotherapy with bismuth preparations; 4 patients with type 2 DM who underwent quadrotherapy with bismuth preparations. Eradication therapy was carried out for 14 days. Evaluation of the effectiveness of eradication using a breath test was carried out 4 weeks after completion of the course of treatment. Eradication success was assessed separately for ITT and PP analyzes. The effectiveness of classical triple eradication therapy in patients with concomitant type 2 DM is 64.4% in the ITT group and 69.05% in the PP: quadrotherapy 73.34 and 80.49%, respectively. The effectiveness of first line eradication therapy is higher in patients without DM compared with groups of patients with concomitant type 2 DM: ITT 83.33%, PP 88.23% and ITT 68.89%, PP 74.70%, respectively. The incidence of side effects in patients with type 2 DM: with the use of classical triple therapy 22.23%, quadrotherapy 31.12%. The data of the study of the efficacy and safety of line I eradication therapy make it possible to recommend the four-component therapy based on bismuth for use in clinical practice, especially in patients with DM.

Cognitive remediation therapy for participants with late‐life schizophrenia

AbstractBackgroundOlder patients with schizophrenia have an elevated risk of dementia; enhancing their cognitive function holds promise for delaying dementia in this population. Cognitive deficits strongly predict function in schizophrenia. Anticholinergic medication burden (ACB) compounds age‐related cognitive declines in late‐life schizophrenia (LLS). Cognitive remediation (CR) improves cognition in schizophrenia, however literature in LLS is sparse. This study examined the effect of CR on cognitive performance in participants with LLS. We also assessed CR tolerability, the interaction between ACB and the effect of CR on cognition.MethodWe adapted CR from our pilot study to a larger group. CR was provided over 12, twice‐weekly, therapist‐guided group sessions. Computerized drill‐and‐practice exercise difficulty levels were adjusted automatically based on performance. Participants were assessed at baseline and at study completion using clinical and cognitive measures.ResultThirty‐four participants were enrolled, 20 (mean (SD) age: 66.0 [5.8]) completed 92.3% (22.14 [1.98]) CR sessions; the ITT group (N=34) attended 72.9% (17.50 [7.23]) sessions. Global cognition did not improve (completers: p=0.80, ITT: p=0.86) with negligible effect size (completers: d=0.08; ITT d=0.04). There was no significant improvement in executive function (completers: p=0.16; ITT: p=0.33). Medication ACB was inversely associated with total MoCA score, accounting for 8.9% of the variance in final MoCA score (p=0.02).ConclusionOverall, CR was well tolerated but did not improve global cognition or executive functioning in this outpatient sample with LLS. A higher ACB was associated with greater cognitive impairment and a poorer response to CR. Future studies need to better characterize potential variables serving to limit the response to CR, including the number and frequency of CR sessions and the role of ACB.

Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma during Treatment with Ixazomib-Thalidomide-Dexamethasone Followed By Ixazomib Maintenance

Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma during Treatment with Ixazomib-Thalidomide-Dexamethasone Followed By Ixazomib Maintenance

77-LB: A Retrospective Analysis of the Association between HbA1c and Continuous Glucose Monitor Use for U.S. Patients with Type 2 Diabetes

Background: Use of real-time continuous glucose monitoring (rtCGM) reduces HbA1c in individuals with type 2 diabetes (T2D) treated with intensive insulin regimens in randomized clinical trials. However, the effects of CGM use on glycemia in T2D patients in real world settings, particularly those treated with less intensive therapies, has not been well studied. Materials and Methods: This large retrospective, observational analysis utilized data from the Optum Research Database (ORD) to assess the glycemic effects of CGM use (any CGM or real-time CGM [rtCGM]) compared with self-monitoring of blood glucoses (SMBG) within a large T2D population treated with intensive insulin therapy (IIT) and non-intensive therapies (NIT), including basal insulin only, and non-insulin medications. Outcomes were changes from baseline in HbA1c up to 6 months post index date in all patients and by treatment regimen. The percentage of patients who achieved ≥1.0 HbA1c reductions was also assessed. Results: Data from 82,983 eligible patients were assessed (Any CGM, n=1,406; rtCGM, n=148; SMBG, n=81,575). Significant HbA1c reductions were observed with Any CGM (-0.46) and rtCGM (-0.72) vs. SMBG (-0.09), ps &amp;lt; 0.001. HbA1c reductions were significant in CGM vs. SMBG users in the ITT (Any CGM, -0.38%; rtCGM, -0.68%, ps&amp;lt;0.001) and NIT groups (Any CGM, -0.67%, p&amp;lt;0.001, and rtCGM, -0.87, p=0.008). Significantly higher percentages of Any CGM and rtCGM vs. SMBG users achieved ≥1.0 HbA1c reductions in the IIT and NIT groups. Effects of Any CGM and rtCGM were attenuated but remained statistically significant in multivariate adjusted models for the overall T2D cohort. Conclusions: Use of CGM (Any CGM or rtCGM) confers notable benefits in improving glycemic control regardless of therapy regimen. These findings support expanding CGM access to the broader T2D population. Disclosure G. J. Norman: Employee; Self; Dexcom, Inc. M. L. Paudel: None. T. Bancroft: None. P. M. Lynch: Employee; Self; Dexcom, Inc.

Abstract No. 52 ▪ FEATURED ABSTRACT Three-year results from the prospective, multicenter VERNACULAR trial: treatment of iliofemoral venous disease with the self-expanding Venovo venous stent

To assess performance and safety of the Venovo venous stent, a self-expanding stent specifically designed for the treatment of iliofemoral vein occlusions. Investigators in the international, multicenter VERNACULAR study enrolled 170 patients—93 post-thrombotic syndrome (PTS) and 77 non-thrombotic iliac vein lesion (NIVL) —at 22 centers in the United States, Europe, and Australia. Primary endpoints were major adverse events (MAEs) through 30 days and 12-month primary patency, defined as freedom from target vessel revascularization and freedom from thrombotic occlusion and duplex-ultrasound derived stenosis >50%. Secondary outcomes included the Venous Clinical Severity Score (VCSS) Pain Assessment, Quality of Life (CIVIQ-20), target lesion revascularization (TLR), and stent fracture assessment (Yale venographic core laboratory) through 36 months. Freedom from MAEs through 30 days was 93.5%, non-inferior to a pre-specified performance goal (PG) of 89% (P = 0.032) while primary patency at 12 months was 88.3%, superior to a PG of 74% derived from the venous stent literature (P < 0.0001). Follow up at two years was 86.4% (147/170 patients). Primary patency at 24 months was 83.2% (90% CI 77.3%, 89.1%); 77.3% for the PTS subgroup and 95.2% for the NIVL patients. Primary patency estimated by Kaplan-Meier survival analysis was 84.3% for the ITT group at 760 days. The 24-month TLR rate was 10.9% resulting in a freedom from TLR of 89.4% (95% CI 83.6%, 93.7%). The mean VCSS Pain Score improved from 0.6 at 12 months to 0.4 (95% CI: 0.46, 0.74) at 24-months with an overall improvement from baseline of 1.9 (median 2.0); CIVIQ-20 scores at two years also improved (15.6 points) from baseline values. No stent fractures were observed at 12 or 24 months. 36-month follow-up is ongoing. The Venovo venous stent was deployed successfully in obstructive iliofemoral vein lesions (acute technical success: 100%). Primary patency was 88.3% at 12 months and 83.2% at 24 months. Reintervention rates were low, with no stent fractures reported through two years. Final, three-year results of the VERNACULAR Study will be presented at SIR 2021.

Therapeutic Effects of Prolonged Release Melatonin (Circadin®) in Patients with Overactive Bladder and Chronic Insomnia in More Than 55 Years Old

Objectives Bladder storage symptoms including nocturia is the most common cause of sleep disturbance in all age groups. Sleep disturbance is also a main cause of nocturia so that sleep recovery can clinically improve nocturia. Melatonin has main action to induce sleep and additional effects of smooth muscle relaxation, free radical scavenging, anti-inflammation, et cetera. This study was evaluated the improvement of sleep quality after administrating prolonged-release melatonin in elderly patients with overactive bladder and chronic insomnia. Methods This clinical trial was performed with a randomized single open study. Thirty-seven patients with overactive bladder and chronic insomnia were initially enrolled in this study. After 4 or 12 weeks treating with 2 mg of prolonged-release melatonin, clinical outcomes were evaluated with OABSS, IPSS, PSQI and WHO 5 well-being index. Results Of the 37 patients, 34 (91.9%) were included in the ITT group and 26 (76.5%) in the PP group. In the primary outcome of PP group, significant improvements were observed in total OABSS and nocturia frequencies at 12 weeks, respectively. Secondary outcome measurement including in voiding, storage symptoms, and total IPSS scores showed the improvement at 4 and 12 weeks and in total and sleep quality PSQI scores at 12 weeks, and in quality of life scores of the WHO 5 well-being index at 12 weeks. Only one (3.8%) adverse event was observed. Conclusions These results suggest clearly that prolonged-release melatonin in elderly patients with overactive bladder and chronic insomnia has the potential to control concomitant voiding and sleep difficulty.

Momelotinib's Spleen, Symptom and Anemia Efficacy Is Maintained in Intermediate/High Risk Myelofibrosis Patients with Thrombocytopenia

Momelotinib's Spleen, Symptom and Anemia Efficacy Is Maintained in Intermediate/High Risk Myelofibrosis Patients with Thrombocytopenia

Abstract CT211: EF-19 - A post-approval registry study of TTFields for the treatment of recurrent glioblastoma (GBM)

Abstract Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. In phase 3 studies leading to FDA approvals, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide, and achieved comparable survival outcome to best standard of care (BSC) when used as monotherapy in recurrent GBM. The aim of the EF-19 study was to confirm the efficacy of TTFields versus BSC for recurrent GBM in the post-approval real-life setting. Method: This non-inferiority, prospective, non-randomized, post approval registry trial enrolled 192 recurrent GBM patients (&amp;gt;21 years, KPS &amp;gt; 70). All patients were treated with TTFields (200 kHz, &amp;gt;18h/day). Eligibility criteria included histological diagnosis of GBM, past treatment with the Stupp protocol for the primary disease and radiological evidence of progression in the supratentorial region. The primary endpoint was overall survival (OS); secondary endpoints included OS in the per protocol (PP) population (&amp;gt;1 course of TTFields or BSC in each respective arm), time to treatment failure and incidence of adverse events. The TTFields patient registry data were compared to OS of all 117 recurrent GBM patients in the BSC group of the EF-11 pivotal trial (Stupp R., et al., EJC 2012). The sample size of 192 patients (10% loss to follow up) was determined based on non-inferiority log-rank test with a two-sided alpha level of 0.05 and a power of 80%, comparing time to event (i.e., death) between patients treated with TTFields and BSC. The analysis was based on true hazard ratio (HR) of 1.0 comparing TTFields to control with an upper one-sided 95% confidence bound of HR is not exceeding 1.375. Result: Median OS in patients treated with TTFields versus EF-11 BSC was 7.4 vs. 6.4 months, p=0.053; HR = 0.64 (95%CI 0.46-0.91, Cox-test P=0.012). In the PP population, the median OS with TTFields versus EF-11 BSC was 8.1 months vs. 6.5 months, respectively; p=0.045; HR 0.65. The results show a significant superiority HR of overall survival between the ITT groups, as superiority 95% confident interval upper limit of the HR was lower than the pre-defined threshold for non-inferiority for interval bound of 1.375. The overall incidence of adverse event was lower in the TTFields arm (67% vs. 95%) vs. EF-11 BSC arm. The median time to treatment failure was longer in the TTFields arm (3.3 months (95% CI 2.6, 3.9)) compared to the BSC arm (1.6 months; 95% CI 1.1, 1.9); HR=0.53 (95% CI 0.41, 0.68, p&amp;lt;0.0001). Skin AE was the most frequently reported AEs in TTFields-treated patients; No unexpected adverse events were reported with TTFields. Conclusion: The EF-19 confirmed the effectiveness and safety of TTFields as monotherapy in recurrent GBM. Citation Format: Jay-Jiguang Zhu, Robert T. O'Donnell, Zvi Ram. EF-19 - A post-approval registry study of TTFields for the treatment of recurrent glioblastoma (GBM) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT211.

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Background: Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET.Methods: Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1–3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life.Results: At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions).Conclusions: Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity.Trial Registration Number (TRN): (Prot. n° 0008872.25-06-2019); RS 919/17.

Long-term effects of acute cadmium exposure on testis immune privilege

Cadmium (Cd) is a widespread and non-biodegradable pollutant of great concern to human health. This element can affect cellular signal transduction and cell-to-cell interaction in the testis. Immune tolerance towards auto- and alloantigens is an important component of testis immunity. It is involved in spermatogenesis and hormone secretion. Plus, the immune tolerance may help to reveal the changes in testis immunity over a long period after Cd exposure. The current research was aimed at investigating the long-term effects of acute Cd exposure on testis immunity by means of elicitation of testicular immune cell composition shift induced by Cd. Cadmium chloride was intraperitoneally injected at 3 mg Cd/kg to mice. After that testis interstitial cells were stained with surface markers for leukocyte and lymphocyte subpopulations (CD45, CD11b, CD3, CD4, CD8, CD25) and analyzed cytofluorimetrically by week 4, 6, 8 and 12 after Cd administration (Cd group). To identify the delayed effects of cadmium on immune tolerance two groups of animals were subjected to intratesticular allotransplantation of neonatal testis (groups ITT and Cd+ ITT). One of the groups was administered with Cd four weeks before the transplantation (Cd+ITT group). I group served as a control that did not undergo any transplantation or Cd injection. For a better demonstration of the phenomenon of immunological tolerance of the testicles, an additional group (UKT group) was used which got grafts under the kidney capsule (non-immune privileged site).Investigation of the cell population showed that CD45+, CD11b+, CD4+, CD8+ cells were permanently present in testicular interstitial tissue in I group. Intratesticular testis transplantation increased the proportion of CD11b+ but did not have such a pronounced effect on CD8+ cells in ITT group. Moreover, the transplantation elevated CD4+ CD25+ cells known for their immunosuppressive property and promoted graft development by week 2 (histological data). Cd injection resulted in severe inflammation that quenched by week 4 (Cd and Cd+ ITT groups). This time point was chosen for transplantation in Cd+ ITT group. Such Cd pretreatment led to a high CD8+ cell proportion and to the delayed appearance of CD4+ CD25+ cells by week 2 (Cd+ ITTgroup). The finding is consistent with the impairment of graft development in Cd+ ITTgroup pretreated with Cd. Observation suggest that Cd pretreatment was associated with disproportion of interstitial immune cell populations which resulted in the impairment of immunoprotective function of the testis. The impairment of testis immunity showed itself only after several weeks of Cd administration, and only when the recipient testis immunity was provoked by alloantigens of donor testes.

3:18 PM Abstract No. 84 Iliac and femoral vein occlusive disease treated with a self-expanding venous stent: 24-month results from the prospective, multicenter VERNACULAR trial

To assess the performance of a self-expanding stent specifically designed for veins (VENOVO Venous Stent) for the treatment of iliac and femoral vein occlusions. The VERNACULAR study was conducted at 22 centers in the United States, Europe, and Australia. The intent-to-treat population included 170 patents, 93 postthrombotic syndrome patients (PTS) and 77 non-thrombotic iliac vein lesion patients (NIVL). Primary endpoints were major adverse events (MAEs) through 30 days and 12-month primary patency, defined as freedom from target vessel revascularization and freedom from thrombotic occlusion and duplex-ultrasound derived stenosis >50%. Secondary outcomes included primary patency, the Venous Clinical Severity Score (VCSS) Pain Assessment, Quality of Life (CIVIQ-20), and target lesion revascularization (TLR) at 24 months. Radiographs were assessed for stent fracture by the venographic core laboratory. Freedom from MAEs through 30 days was 93.5%, non-inferior to a performance goal (PG) of 89% (P = 0.032) while primary patency at 12 months was 88.3%, superior to a PG of 74% derived from the venous stent literature (P < 0.0001). Follow-up at two years was 86.4% (147/170 patients). Primary patency at 24 months was 83.2% (90% CI 77.3%, 89.1%); 77.3% for the PTS subgroup and 95.2% for the NIVL patients. Primary patency estimated by Kaplan-Meier survival analysis was 84.3% for the ITT group at 760 days. The 24-month TLR rate was 10.9% resulting in a freedom from TLR of 89.4% (95% CI 83.6%, 93.7%). The mean VCSS Pain Score improved from 0.6 at 12 months to 0.4 (95% CI: 0.46, 0.74) at 24-months with an overall improvement from baseline of 1.9 (median, 2.0); CIVIQ-20 scores at two years also improved (15.6 points) from baseline values. No stent fractures were observed at 12 or 24 months. Observations from the VERNACULAR trial at two years supported the 12-month results. The VENOVO stent could be deployed successfully in obstructive iliofemoral vein lesions. Primary patency was 88.3% at 12 months and 83.2% at 24 months. Reintervention rates were low, with no stent fractures reported through two years.

Abstract P2-15-10: Utidelone plus capecitabine versus capecitabine for heavily pretreated metastatic breast cancer and CIPN: Analysis of a single centre cohort

Abstract Objective In BG01-1323L trial, Utidelone, a novel genetically engineered epothilone analogue, plus capecitabine showed improved progression-free survival and overall survival in heavily pretreated metastatic breast cancer prior to anthracycline and taxane. Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common dose-limiting toxicity of utidelone plus capecitabine. The most samples were provided and CIPN related germline mutations were analyzed in our single centre. Recent study indicated ganglioside-monosialic acid (GM1) could decrease the incidence and severity of taxane-induced peripheral neuropathy. The aims of this study were to assess the efficacy of utidelone plus capecitabine in our centre and predictive role of mutations for CIPN, further to identify whether GM1 or Trivitamin B (IIIvB) improved CIPN. Methods Fifty-four eligible female patients with metastatic breast cancer refractory to anthracycline and taxane were enrolled in our single centre in Phase 3 BG01-1323L trial. We randomly assigned to 39 cases in utidelone plus capecitabine and 16 cases in capecitabine alone until disease progression or unacceptable toxicity occurred. Progression-free survival and overall survival were assessed in our centre with the Kaplan-Meier product-limit method and Safety including neurotoxicity was both assessed in all participants and in our single centre. SNP were detected in germline panel including ABCB1, CDA, CYP19A1, CYP 2D6, DPYD, ERCC1, GSTP1, NQO1, TP53, TYMS and UGT1A1 and 363-genes panel was detected by NGS only in our centre. Results In our single centre, median progression-free survival in the utidelone plus capecitabine group was 139 days compared with 137 days in the capecitabine alone group, p=0.642. Median overall survival improved in combined therapy (626 days vs 409 days, p=0.026). Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group. Compared with the ITT group, more grade1/2 CIPN (87.2% [34/39] in our centre vs 59% [89/270] in ITT) but less grade 3 (12.8% [5/39] in our centre vs 22% [92/270] in ITT) occurred in our single centre cohort. The potential reason for this difference of CIPN G3 was the palliative treatment target CIPN with GM1 or IIIvB in our single centre. Our analysis revealed that median time and duration of UIPN G3 was 10.29 weeks and 3.12 weeks in ITT and 15.67 weeks and 0.86 weeks in our single centre. Treatment with GM1 or IIIvB was associated with delay the median of CIPN G3 (10.29 weeks vs. 15.67 weeks) and reduction of the duration time (3.12 weeks vs. 0.86 weeks) in our centre compared to the ITT cohort. A tendency to extend the time of CIPN I/II was observed between GM1 and IIIvB groups (Grade I: 95.13 days vs 87.57 days, Grade II: 69.09 days vs 48.51 days). No associated germline SNP was found in Grade 3 CIPN and AXIN2, ATM and SMARCA4 mutation was associated with increased incidence CIPN by 363-gene panel. Conclusion Utidelone plus capecitabine was more efficacious compared with capecitabine alone for progression-free survival with mild toxicity except for CIPN, less grade 3 CIPN was assessed in our single centre with GM1 and IIIvB, further investigation need to validate manageable efficacy of GM1 or IIIvB in CIPN in patients with utidelone plus capecitabine, as an effective option for patients with metastatic breast cancer. Citation Format: Junnnan Xu, Tao Sun. Utidelone plus capecitabine versus capecitabine for heavily pretreated metastatic breast cancer and CIPN: Analysis of a single centre cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-10.

Carfilzomib-Revlimid-Dexamethasone Vs. Carfilzomib-Thalidomide-Dexamethasone Weekly (After 2 Twice Weekly Cycles) Followed By Carfilzomib Maintenance Vs. Control in Transplant Non-Eligible Patients with Newly Diagnosed Multiple Myeloma (NDMM) - Interim Efficacy Analysis of Combined Data (AGMT MM-02)

Carfilzomib-Revlimid-Dexamethasone Vs. Carfilzomib-Thalidomide-Dexamethasone Weekly (After 2 Twice Weekly Cycles) Followed By Carfilzomib Maintenance Vs. Control in Transplant Non-Eligible Patients with Newly Diagnosed Multiple Myeloma (NDMM) - Interim Efficacy Analysis of Combined Data (AGMT MM-02)

124O - KEYNOTE-181: Pembrolizumab vs chemotherapy in patients (pts) with advanced/metastatic adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus as second-line (2L) therapy

124O - KEYNOTE-181: Pembrolizumab vs chemotherapy in patients (pts) with advanced/metastatic adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus as second-line (2L) therapy