Grade 3b Research Articles

Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2.

TPS7592 Background: In pts with newly diagnosed DLBCL, standard treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has a 5-year progression-free survival (PFS) rate of 67.0%, 58.4%, and 45.8% for International Prognostic Index (IPI) 2, 3, and 4–5, respectively (Ruppert et al, Blood 2020). Epcoritamab is a subcutaneously administered, bispecific antibody that binds CD3 on T cells and CD20 on B cells, inducing potent and selective T-cell–mediated killing of malignant CD20+ B cells (Hutchings et al, Lancet 2021). Epcoritamab monotherapy demonstrated deep and durable responses (overall response rate [ORR], 63%; complete response rate, 39%) and was generally well tolerated in pts with relapsed/refractory (R/R) aggressive, large B-cell lymphoma (LBCL) (Thieblemont et al, J Clin Oncol 2022). Results from an ongoing phase 1/2 study in high-risk pts with newly diagnosed DLBCL (EPCORE NHL-2 arm 1; NCT04663347) show that epcoritamab + R-CHOP has promising efficacy and a manageable safety profile in high-risk pts with IPI 3–5. Among efficacy-evaluable pts (n = 31), ORR was 100% and complete metabolic response (CMR) was 77%; cytokine release syndrome (CRS) events (n = 17/33; 52%) were mostly low-grade, had predictable timing, and did not lead to treatment discontinuation (Falchi et al, ASCO 2022, abstract 7523). These encouraging data support further evaluation of epcoritamab + R-CHOP for the treatment of newly diagnosed DLBCL. Methods: This phase 3, global, multicenter, open-label study (NCT05578976) evaluates the efficacy and safety of epcoritamab + R-CHOP in adults newly diagnosed with one of the following CD20+ DLBCL (de novo or transformed from follicular lymphoma [FL]): 1) DLBCL, not otherwise specified (NOS); 2) high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement; 3) T-cell/histiocyte–rich LBCL; 4) Epstein-Barr virus–positive DLBCL, NOS; or 5) FL grade 3b. Other key eligibility criteria include IPI ≥2 (pts with IPI 2 not to exceed ~30% of total pts), ECOG PS 0–2, and ≥1 measurable disease site. Approximately 900 pts will be randomized 2:1 to either epcoritamab + R-CHOP (6 cycles, followed by 2 cycles of epcoritamab) or R-CHOP (6 cycles, followed by 2 cycles of rituximab). The primary efficacy endpoint is PFS in pts with IPI 3–5 (based on IRC assessment per Lugano criteria). The secondary efficacy endpoints are PFS in pts with IPI 2–5, event-free survival, CMR, overall survival, and minimal residual disease negativity. Safety endpoints include incidence and severity of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (CRS, immune cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome. Enrollment began in January 2023 globally. Clinical trial information: NCT04663347 , NCT05578976 .

Prognostic values of circulating TREM2+ and ARG1+ Mreg cells in adults with treatment‐naïve diffuse large B‐cell lymphoma

Introduction: Novel Trem2+ (triggering receptor expressed on myeloid cells 2) and Arg1+ (arginase 1) regulatory myeloid cells (Mreg) that lead to the dysfunction of CD8+ T cells and facilitate tumor growth were recently discovered in a murine cancer model by Yonatan Katzenelenbogen et al. However, as the roles of Mreg cells have never been examined in human cancer patients, we aim to elucidate the clinical impact of circulating Mreg cells on patients with treatment-naive B-cell NHL, especially focusing on DLBCL. Methods: This prospective, observational study enrolled 102 adults with newly diagnosed and treatment-naïve B-cell NHL, including 62 DLBCL, 25 FL (4 grade 3B), 4 MCL, 4 MZL, 2 LPL, 2 BL, and 3 mature B-cell neoplasms, from December 2020 to November 2022. We obtained human circulating TREM2+ and ARG1+ Mreg cells from freshly isolated peripheral blood and calculated their percentages among CD45+ and CD15- cells by flow-cytometry analysis. Non-stain (NS) and fluorescence minus one (FMO) controls were used for gating positive levels of surface TREM2 and intracellular ARG1, respectively. Results: Among 102 patients with B-cell NHL, those with high-risk IPI had significantly higher percentages of circulating Mreg cells than patients with intermediate or low-risk IPI (5.46% vs. 1.71% vs. 0.63%, P H vs. L < 0.001, P H vs. I = 0.032, P I vs. L = 0.005); patients with aggressive subtypes (including grade-3B FL) had significantly higher percentages of circulating Mreg cells than patients with indolent subtypes (1.89% vs. 0.93%, P = 0.023). For 62 DLBCL patients, those with high IPI risk (9.18% vs. 1.25%, P < 0.001), bulky mass ≥ 7.5 cm (5.08% vs. 1.18%, P = 0.057), or DEL (5.13% vs. 1.21%, P = 0.036) had significantly higher percentages of circulating Mreg cells (Figures A–F). More importantly, DLBCL patients with circulating Mreg cells ≥4.5% had significantly worse PFS and OS than those with Mreg cells <4.5% after a median follow-up of 14 months (Figures G and H); when utilizing multivariate Cox regression analysis, “circulating Mreg cells ≥4.5%” remained an independent prognostic factor for both PFS and OS after adjusting for confounding factors, including age, sex, high-risk IPI, bulky mass ≥7.5 cm, BM involvement, non-GCB type, and DEL. The research was funded by: The research was funded by grants from: (1) the Taiwan Ministry of Science and Technology (MOST 111-2314-B-075-037), (2) Taipei Veterans General Hospital (V110B-012), (3) the Chong Hin Loon Memorial Cancer and Biotherapy Research Center, (4) the Melissa Lee Cancer Foundation, and (5) the Taiwan Clinical Oncology Research Foundation. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers No conflicts of interests pertinent to the abstract.

SUNMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin vs rituximab plus gemcitabine and oxaliplatin in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.

TPS7586 Background: Aggressive non-Hodgkin lymphomas (aNHL) are a diverse group of neoplasms, of which diffuse large B-cell lymphoma (DLBCL) is the most common subtype (Thandra, 2021). Patients (pts) with relapsed/refractory (R/R) DLBCL after one prior therapy who are unable to receive, or relapse after an autologous stem cell transplant (ASCT) and/or chimeric antigen receptor T-cell therapy have a poor prognosis (Salles, 2019; Di Blasi, 2022). Mosunetuzumab (Mosun) is an off-the-shelf CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells (Sun, 2015), with promising efficacy and safety as a single agent, as shown in a Phase I trial in pts with B-cell NHL, including aNHL (Budde, 2022). Mosun has also shown promising safety and efficacy in combination with polatuzumab vedotin (Pola), a CD79b targeted antibody-drug conjugate that delivers the microtubule-disrupting agent monomethyl auristatin E directly to B cells (Dornan, 2009), in a Phase Ib/II trial in pts with R/R aNHL (Budde, ASH 2021). Methods: SUNMO (NCT05171647) is a randomized, open-label, global Phase III trial evaluating the efficacy and safety of subcutaneous Mosun + intravenous (IV) Pola (M-Pola) vs IV rituximab + gemcitabine and oxaliplatin (R-GemOx) in pts with R/R aNHL. Eligible pts have CD20-positive R/R aNHL (DLBCL not otherwise specified [NOS], high-grade B-cell lymphoma double/triple hit or NOS, transformed follicular lymphoma [trFL], or Grade 3B FL), ECOG performance status 0–2, and ≥1 prior systemic therapy (if only one prior line of therapy, pts must be ineligible for ASCT). Exclusion criteria include prior treatment with CD20-directed bispecific antibodies, R-GemOx, or GemOx; prior allogeneic stem cell transplant; and any central nervous system involvement of lymphoma. Pts will be randomized 2:1, stratified by the number of prior lines of therapy (1 vs &gt; 1) and response to last therapy (relapsed vs refractory) to receive M-Pola or R-GemOx IV for a fixed duration of up to 8 cycles (6 cycles for Pola; M-Pola, 21-day cycles; R-GemOx, 14-day cycles). The primary endpoint is progression-free survival (PFS) determined by an independent review facility (IRF). Secondary endpoints include overall survival; IRF- and investigator (INV)-assessed complete response (CR) rate, objective response rate, and duration of response/CR; INV-assessed PFS; patient-reported outcomes; and safety. Biomarker analyses include pre-specified prognostic subsets from baseline biopsies and circulating tumor DNA at baseline and during treatment. Enrollment is ongoing, and an estimated 75 sites globally will enroll approximately 222 pts (M-Pola, 148 pts; R-GemOx, 74 pts). Clinical trial information: NCT05171647 .

SUBCUTANEOUS EPCORITAMAB INDUCES DEEP, DURABLE COMPLETE REMISSIONS IN RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA: LONGER FOLLOW‐UP FROM THE PIVOTAL EPCORE NHL‐1 TRIAL

SUBCUTANEOUS EPCORITAMAB INDUCES DEEP, DURABLE COMPLETE REMISSIONS IN RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA: LONGER FOLLOW‐UP FROM THE PIVOTAL EPCORE NHL‐1 TRIAL

Effect of follow-up time on the ability of subcutaneous epcoritamab to induce deep and durable complete remissions in patients with relapsed/refractory large B-cell lymphoma: Updated results from the pivotal EPCORE NHL-1 trial.

7525 Background: Outcomes are poor for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Effective treatments (tx) that drive deep, durable responses and long-term benefit are needed. In the pivotal EPCORE NHL-1 trial (NCT03625037), single-agent epcoritamab (epcor) showed high complete response (CR) and MRD-negativity rates, a median duration of response (mDoR) not reached (NR) in pts who achieved CR, and a manageable safety profile as an off-the-shelf, subcutaneous (SC), CD3xCD20 T-cell–engaging bispecific antibody (Thieblemont et al, JCO 2022). We present updated results with longer follow-up in a challenging-to-treat population. Methods: Pts with R/R CD20+ LBCL received SC epcor (step-up priming and intermediate doses followed by 48-mg full doses) in 28-d cycles (Cs): QW, C1–3; Q2W, C4–9; Q4W, C≥10 until PD or unacceptable toxicity. Results: As of Nov 18, 2022, of 157 pts (median age, 64 y) with LBCL (including DLBCL [n=139], HGBCL [n=9], PMBCL [n=4], and FL grade 3B [n=5]; 13/99 double/triple-hit by FISH), 36 remain on tx. Pts had a median of 1.6 y from initial diagnosis to first dose and a median of 3 (range, 2–11) prior tx lines; 61% of pts had primary refractory disease, and 39% had prior CAR T, of whom 75% progressed ≤6 mo of tx. Median follow-up was 20 mo (range, 0.3+ to 28.2). Pts received a mean of 9.1 cycles. LBCL overall response and CR rates were 63.1% and 39.5%, respectively, and were consistent for DLBCL (61.9% and 39.6%). The mDoCR was 20.8 mo. Median time to CR was 2.7 mo; 8 pts converted from partial response to CR at ≥36 wk. Median overall survival (mOS) was 18.5 mo (95% CI, 11.7–NR), with an estimated 58% of pts alive at 12 mo. mOS was NR in pts who achieved CR. Additional outcomes for pts with CR are shown in Table. The most common TEAEs of any grade (G) were: CRS 51%, neutropenia 24%, pyrexia 24%, fatigue 23%, nausea 22%, and diarrhea 21%. Nine pts (6%) had G1–2 ICANS, and 1 pt had a G5 event with confounding factors. Fatal TEAEs occurred in 15 pts; 2 were considered related (COVID-19, ICANS). CRS was predominantly low grade (48% G1–2; 3% G3) and occurred following the first full dose (C1D15). One pt discontinued tx due to G1 CRS. Total metabolic tumor volume (TMTV) data will be presented. Conclusions: These data with longer follow-up reaffirm single-agent SC epcor induces durable CRs with improved outcomes and a manageable safety profile. No new safety signals were observed in these hard-to-treat pts. These impressive data support the ongoing phase 3 studies evaluating epcor across different lines of tx and in various combinations. Clinical trial information: NCT03625037 . [Table: see text]

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: In pts with newly diagnosed DLBCL, standard treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has a 5-year progression-free survival (PFS) rate of 67.0%, 58.4%, and 45.8% for International Prognostic Index (IPI) 2, 3, and 4–5, respectively (Ruppert et al., Blood 2020). Epcoritamab is a subcutaneously administered, bispecific antibody that binds CD3 on T cells and CD20 on B cells, inducing potent and selective T-cell–mediated killing of malignant CD20+ B cells (Hutchings et al., Lancet 2021). Epcoritamab monotherapy demonstrated deep and durable responses (overall response rate [ORR], 63%; complete response rate, 39%; median duration of response, 12 months) and was generally well tolerated in pts with relapsed/refractory (R/R) aggressive, large B-cell lymphoma (LBCL) (Thieblemont et al., J Clin Oncol 2022). Results from an ongoing phase 1/2 study in high-risk pts with newly diagnosed DLBCL (EPCORE NHL-2 arm 1; NCT04663347) show that epcoritamab + R-CHOP has promising efficacy and a manageable safety profile in high-risk pts with IPI 3–5. Among efficacy-evaluable pts (n = 31), ORR was 100% and complete metabolic response (CMR) was 77%; cytokine release syndrome (CRS) events (n = 17/33; 52%) were mostly low-grade, had predictable timing, and did not lead to treatment discontinuation (Falchi et al., ASCO 2022, abstract 7523). These encouraging data support further evaluation of epcoritamab + R-CHOP for the treatment of newly diagnosed DLBCL. Methods: This phase 3, global, multicenter, open-label study (NCT05578976) evaluates the efficacy and safety of epcoritamab + R-CHOP in adults newly diagnosed with one of the following CD20+ DLBCL (de novo or transformed from follicular lymphoma [FL]): 1) DLBCL, not otherwise specified (NOS); 2) high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement; 3) T-cell/histiocyte–rich LBCL; 4) Epstein-Barr virus–positive DLBCL, NOS; or 5) FL grade 3b. Other key eligibility criteria include IPI ≥2 (pts with IPI 2 not to exceed ∼30% of total pts), ECOG PS 0–2, and ≥1 measurable disease site. Approximately 900 pts will be randomized 2:1 to either epcoritamab + R-CHOP (6 cycles, followed by 2 cycles of epcoritamab) or R-CHOP (6 cycles, followed by 2 cycles of rituximab). The primary efficacy endpoint is PFS in pts with IPI 3–5 (based on IRC assessment per Lugano criteria). The secondary efficacy endpoints are PFS in pts with IPI 2–5, event-free survival, CMR, overall survival, and minimal residual disease negativity. Safety endpoints include incidence and severity of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (CRS, immune cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome). Enrollment began in January 2023 globally. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved. The research was funded by: This study was funded by AbbVie and Genmab. Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, immunotherapy Conflicts of interests pertinent to the abstract. L. H. Sehn Consultant or advisory role AbbVie, Amgen, AstraZeneca, BeiGene, BMS/Celgene, Genentech/Roche, Incyte, Janssen, Kite/Gilead, Merck, Seattle Genetics Research funding: Teva, Roche/Genentech M. Chamuleau Consultant or advisory role AbbVie, Novartis, Incyte Research funding: BMS, Gilead, GenMab G. Lenz Consultant or advisory role Roche, Gilead, Janssen, Bayer, BMS, Novartis, AbbVie, Incyte, Genmab, Karyopharm, Constellation, ADC Therapeutics, Sobi, Miltenyi, PentixaPharm, Genase, Immagene, Hexal, Lilly Research funding: Janssen, Bayer, MorphoSys, AstraZeneca Other remuneration: Invited Speaker: Roche, BMS, Novartis, AbbVie, Incyte, Sobi, Hexal M. R. Clausen Consultant or advisory role AbbVie, Genmab, Janssen and Kite/Gilead C. Haioun Consultant or advisory role AbbVie, Genentech/Roche, Incyte, Kite/Gilead, Miltenyi A. Davies Honoraria: Roche, Kite, Incyte, BMS, AstraZeneca, AbbVie, Genmab Research funding: Roche, AstraZeneca, MSD, Cellcentric Educational grants: Roche T. Oki Employment or leadership position: AbbVie E. Szafer-Glusman Employment or leadership position: AbbVie R. Conlon Employment or leadership position: AbbVie Stock ownership: AbbVie H. Chiou Employment or leadership position: AbbVie D. Ipe Employment or leadership position: AbbVie B. Elliot Employment or leadership position: Genmab Stock ownership: Genmab J. Wu Employment or leadership position: AbbVie G. Salles Consultant or advisory role AbbVie, Bayer, BeiGene, BMS/Celgene, Epizyme, Genentech/Roche, Genmab, Incyte, Janssen, Kite/Gilead, Loxo, Miltenyi, MorphoSys, Novartis, Rapt, Regeneron, Takeda

Long-term efficacy and safety of pembrolizumab with R-CHOP as first-line therapy for DLBCL.

7561 Background: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) represents the historical 1st line treatment standard for DLBCL but fails to cure about 1/3 of patients. While generally ineffective in relapsed DLBCL-NOS, checkpoint inhibitors may have greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus RCHOP, noting objective responses in 90% of patients (CR 77%) and a 2-year progression-free survival (PFS) of 83%. We now report 5 year follow up of our study. Methods: Patients age &gt; 18 with untreated DLBCL or grade 3b follicular lymphoma, intended to receive 6 cycles of R-CHOP, were eligible. Pembrolizumab 200 mg IV with R-CHOP was given in 21-day cycles for 6 cycles. For this updated analysis, progression and survival events, and immune-related toxicities, are reported. Additionally, prognostic factors including tumor PD-L1 expression (Qualtek/Merck) were re-analyzed. Results: 30 patients were treated (13/30 with IPI 3-5). Median follow up is now 4.8 years (95% CI, 4.5-5.4). Since our initial report (Smith BJH 2019) we have observed 1 additional relapse (alive after CAR-T therapy) and 2 deaths in remission (1 urothelial carcinoma, 1 respiratory failure in the setting of progressive ILD). 5-year PFS is 71% (CI, 54-94%) and 5-year overall survival 83% (CI, 71-98%). During the study period and at long term follow up, there were 8 total immune-related adverse events (IRAEs) among 7 patients (23%) (Table). Four were treatment-emergent AE (occurred within 90 days of completing treatment): grade 1 hyperthyroidism, grade 2 hyperthyroidism, grade 3 pneumonitis, and grade 3 rash. There were 4 late IRAEs: colitis, paraneoplastic pemphigus, rheumatoid arthritis, and Graves’ disease, occurring at 3, 5, 8, and 46 months after completing treatment, respectively. PD-L1 tumor expression was documented in 19 of 23 (83%) tested patients. At long-term follow up, none of the 19 patients who had any PD-L1 expression have relapsed. Two out of the 4 patients with no PD-L1 expression have relapsed. On univariate analysis, PD-L1 H-score &gt;0 (p&lt;0.0001) was associated with improved PFS. Conclusions: At 5 year follow-up, pembrolizumab plus R-CHOP has led to durable responses in most patients with the best outcomes in PDL1-expressing disease. Furthermore, the safety profile was manageable, with a low rate of grade 3 or higher IRAEs (10%) and no consistent pattern of late events. These data support ongoing strategies incorporating PD-1/PDL-1 inhibitors in 1st line DLBCL therapy and confirmation of predictive biomarkers including tumor PD-L1 expression. Clinical trial information: NCT02541565 . [Table: see text]

Urinary tract injuries during surgery for placenta accreta spectrum disorders

ObjectiveThe main purpose of this study was to report the incidence of lower urinary tract injuries (UTI) during cesarean section (CS) hysterectomy in cases of Placenta Accreta Spectrum (PAS) disorders.Study designRetrospective analysis including all women with a prenatal diagnosis of PAS between January 2010 and December 2020. A dedicated multidisciplinary team was involved to define a tailored management for each patient. All relevant demographic parameters, risk factors, degree of placental adhesion, type of surgery, complications and operative outcomes were reported. ResultsOne hundred and fifty-six singleton gestations with a prenatal diagnosis PAS were included in the analysis. 32.7% of cases were classified as PAS 1 (grade 1-3a FIGO classification), 20.5% as PAS 2 (grade 3b FIGO classification) and 46.8% as PAS 3 (grade 3c FIGO classification). A CS hysterectomy was performed in all cases. Surgical complication occurred in seventeen cases (0% in PAS 1, 12.5% in PAS 2 cases and in 17.8% in PAS 3). The incidence of UTI in our series was 7.6% in all women with PAS, including 8 cases of bladder and 12 of ureteral lesion, and 13.7 % in those with PAS 3 only. ConclusionDespite advances in prenatal diagnosis and management, surgical complications, mainly those involving the urinary system, still occur in a significant proportion of women undergoing surgery for PAS. The findings from this study highlight the need for a multidisciplinary management of women with PAS in centers with high expertise in prenatal diagnosis and surgical management of these conditions.

(477) Ablation Vaginectomy is a Safe and Effective Technique in Transmasculine Gender Affirmation Surgery

Abstract Introduction Genital gender affirmation surgery ameliorates gender incongruence with the aim to align an individual’s genital appearance more closely to their experienced gender identity. Vaginectomy is commonly requested because it allows closure of the vaginal vault resulting in a masculine appearance to the perineum. Vaginectomy also allows a more appealing sac-like scrotoplasty and may reduce the risk of urethral complications. Transvaginal, laparoscopic (often combined with transvaginal) and robotically assisted approaches have been described. The transvaginal approach involves the excision of vaginal mucosa but blood loss may be significant and there is a risk of injury to adjacent organs like the bladder or rectum. Alternatively, the vaginal mucosa can be obliterated by high power electrocautery without excision. This technique has not been formally described in the literature before. Objective Pilot study to describe the technique for ablation vaginectomy (AV) and to assess the safety and efficacy of AV compared to traditional transvaginal excision vaginectomy (EV). Methods Retrospective review of a comprehensive prospective database and supplemented by medical records of transgender and non-binary persons requesting vaginectomy for gender affirmation surgery. AV was performed using high power electrocautery while EV was by a transvaginal approach. Follow-up was 30 days post-surgery. Data were reported as mean (standard error) unless specified otherwise. Results A hundred and thirty-seven patients were included in the study (62 following AV, 75 following EV). The median age (interquartile range) of both cohorts were similar [AV, 38 years (29-48); EV 37.7 years (31.5-43)]. Patients who underwent AV had a higher BMI but despite this, they had a lower intra-operative blood loss (99.8 ± 12.7mL vs 646.7 ± 63.4mL) and post-operative drain loss (90.9 ± 11.6mL vs 242.8 ± 23.6mL). More patients following EV required a transfusion (n=11) of 2.34 ± 0.5 units of packed red cells. Six patients had an intraoperative complication during EV (none for AV). Two patients had a recognised urethral perforation (one combined with a bladder injury) and 3 others had a bladder injury. All were repaired at the time. Complication rates after 30 days were similar although there was a trend for higher complications following EV (24% vs 11.3%, p=0.06). These were all related to bleeding and haematoma formation with 3.4% (AV cohort) and 8% (EV cohort) Clavien-Dindo grade 3b complications. Conclusions AV may be a feasible and safe approach when requested for gender affirmation surgery. Further prospective data with longer follow-up are required. Disclosure No

Follicular lymphoma grade 3B: low grade, high grade or should we skip the grade?

Not available.

Evidence-Based Classification for Post-bariatric Weight Regain from a Benchmark Registry Cohort of 18,403 Patients and Comparison with Current Criteria.

There is a need for a standardized, evidence-based classification of post-bariatric weight-regain, to investigate and compare revision procedures and to advice and treat patients in an evidence-based way. We used standard deviations (SD) of the highest (1-2years) and latest (> 2years) percentage total weight loss (%TWL) results after primary bariatric surgery from the Dutch Audit for Treatment of Obesity (DATO) bariatric registry as benchmarks for (above) average (≥ - 1SD), poor (- 1SD to - 2SD) and insufficient (< - 2SD) weight loss. Weight regain maintaining (above) average weight loss was called grade 1, weight regain towards poor weight loss grade 2, towards insufficient weight loss grade 3, with subgrades 2a/3a for below average weight loss from the start, and 2b/3b for weight regain from (above) average to below average weight loss. Patient characteristics and diabetes improvement/impairment were compared. Sensitivity and specificity of 14 existing weight regain criteria were calculated. We analyzed 93,465 results from 38,830 patients (77.1% gastric bypass, 22.5% sleeve gastrectomy). The - 1SD thresholds for early and late weight loss approximated 25%TWL and 20%TWL, the - 2SD threshold for late weight loss 10%TWL. Weight regain could be analyzed for 18,403 patients (2.5-5.2years follow-up). They regained mean 6.7kg (5.4%TWL), with 66.8% grade 1 weight regain, 7.2% grade 2a, 7.4% grade 2b, 2.1% grade 3a, and 0.6% grade 3b. There were significant differences in comorbidities, gender, age, weight regain, diabetes impairment, and diabetes improvement across grades. Weight regain criteria from literature were extremely divers. None had high sensitivity. The DATO classification for post-bariatric weight regain combines the extent of weight regain with evidence-based endpoints of weight loss. It differentiated weight regain maintaining (above) average weight loss, two intermediate grades, gradual weight regain with below average weight loss from the start (primary non-response) and steep weight regain towards insufficient weight loss (secondary non-response). The classification is superior to existing criteria and well supported by evidence.

Renal Function following Fluorescein Angiography in Diabetic Patients with Chronic Kidney Disease.

To evaluate the effect of fluorescein dye usage on renal function in patients with diabetic retinopathy (DR) and chronic kidney disease (CKD). Diabetic patients with retinopathy who were candidate for fundus fluorescein angiography (FA) were evaluated for serum creatinine and urea levels within five days prior to performing the FA. Serum creatinine levels of 1.5 mg/dl or more in males and 1.4 mg/dl or more in females were both identified as CKD and were included in the study. An increase of 0.5 mg/dl or 25% in creatinine after FA was considered as contrast-induced acute kidney injury (AKI). Estimated glomerular filtration rate (eGFR) was also calculated for all patients using a CKD-Epi formula. CKD grading was determined based on eGFR values. Forty-two patients agreed to participate, of which 23 (54.8%) were male. Seventeen patients were identified with grade 3a or lower CKD, 12 with grade 3b, 11 with grade 4, and two with grade 5 CKD. Considering all grades of CKD, the mean blood urea before and after angiography was 58.48 26.7 and 57 27.81 mg/dl, respectively (P = 0.475). The mean serum creatinine before and after the test was 1.89 1.04 and 1.870.99 mg/dl, respectively (P = 0.993). The mean eGFR before and after the test was 44.024 23.5447 and 43.850 21.8581 mL/min/1.73 m2 (P = 0.875). According to the findings of this study, FA does not seem to further deteriorate kidney function in patients with diabetic associated CKD.

Analysis of stone-free rates and residual fragment sizes following standard percutaneous nephrolithotomy: mistakes in the treatment of non-opaque kidney stones

Our presented study aimed to evaluate the possible effects of stone opacity, on both the success of percutaneous nephrolithotomy and the sizes of residual fragments following the procedure. Medical records of patients undergoing PCNL treatment for kidney stones at our clinic between July 2014 and May 2022 were evaluated in a retrospective manner. A total sample size of 304 patients with the required criteria was included. Patients were divided into two groups based on the radiopacity status of the stones assessed in the kidney-ureter-bladder graphy (KUB) [Group O (n = 211): opaque, Group N (n = 93): non-opaque)]. Demographic data, laboratory results, and surgical follow-up information were comparatively evaluated between groups. The mean age and percentage of female patients were higher in Group N (45.2 vs. 25,1%; p < 0.001). Also, patients in this group were associated with more comorbidities. No significant difference was present regarding stones' laterality, size, surface area, and localization. Cases in the Group N group demonstrated higher median hemoglobin reduction [1.7 (IQR = 1.2-2.5) vs. 2 (IQR = 1.6-2.6); p = 0.047]. The stone-free rates in Group O patients were higher (67.8% vs. 53.8%; p = 0.014). The size of the residual fragments was meaningfully larger in Group N cases [8 (IQR = 7-13) vs. 10 (IQR = 8-16); p = 0.032]. Finally, no significant difference was observed between the groups regarding both minor (as grade 3a and below) and major (grade 3b and above) assessed by the Modified Clavien-Dindo Classification. Our data show that treatment of patients with so-called non-opaque kidney stones by PCNL results in low SFR and larger residual fragments, which is due to a variety of errors that should be avoided by appropriate measures.

V08-02 ROBOTIC AUGMENTATION CYSTOPLASTY: 1-YEAR OUTCOME OF THE ANTERIOR AND POSTERIOR APPROACHES

You have accessJournal of UrologyCME1 Apr 2023V08-02 ROBOTIC AUGMENTATION CYSTOPLASTY: 1-YEAR OUTCOME OF THE ANTERIOR AND POSTERIOR APPROACHES Chi Hang Yee, Phoebe Cl Lam, Yuek Lam Hong, Pui Tak Lai, Yuk Him Tam, Timothy Chang Kidd Ng, Steffi Kar Kei Yuen, Mandy Ho Man Tam, Chi Kwok Chan, Ka Lun Lo, Jeremy Yuen Chun Teoh, Peter Ka Fung Chiu, and Chi Fai Ng Chi Hang YeeChi Hang Yee More articles by this author , Phoebe Cl LamPhoebe Cl Lam More articles by this author , Yuek Lam HongYuek Lam Hong More articles by this author , Pui Tak LaiPui Tak Lai More articles by this author , Yuk Him TamYuk Him Tam More articles by this author , Timothy Chang Kidd NgTimothy Chang Kidd Ng More articles by this author , Steffi Kar Kei YuenSteffi Kar Kei Yuen More articles by this author , Mandy Ho Man TamMandy Ho Man Tam More articles by this author , Chi Kwok ChanChi Kwok Chan More articles by this author , Ka Lun LoKa Lun Lo More articles by this author , Jeremy Yuen Chun TeohJeremy Yuen Chun Teoh More articles by this author , Peter Ka Fung ChiuPeter Ka Fung Chiu More articles by this author , and Chi Fai NgChi Fai Ng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003306.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To investigate the outcome of robotic augmentation cystoplasty as the treatment of refractory cystitis due to ketamine abuse, and to compare the results of the anterior versus posterior surgical approaches. METHODS: This is a prospective series of patients with refractory lower urinary symptoms and a small contracted bladder due to ketamine-associated cystitis, who were indicated for augmentation cystoplasty. Robotic augmentation cystoplasty was performed with either the conventional anterior clamp cystoplasty approach, or the posterior U-flap M-configuration cystoplasty technique. Peri-operative data were collected and one-year outcome assessment was performed including functional bladder capacity (FBC) with urodynamic study, renal function and analgesic consumption. RESULTS: Between July 2011 and April 2021, 24 patients underwent robotic augmentation cystoplasty. Mean age was 32.0 ± 5.8 years. Additional procedures included 4 ureteric-reimplantations and 1 ileal interposition. Significant FBC improvement was observed 1 year after the operation (pre-operative 56.7 ± 36.2 ml, post-operative 328.5 ± 163.8, p<0.0001). FBC of anterior approach and posterior approach at 1 year was 312.5 ± 163.6 ml and 362.5 ± 161.4 ml respectively (p=0.276). Mean operative time was 272.0 ± 103.3 minutes. Analgesic requirement was decreased after the operation (pre-operative 19 patients, post-operative 4 patients; p<0.0001). Post-operative complications included 8 Clavien-Dindo grade 1 incidences and 1 Clavien-Dindo grade 3B incidence (small bowel obstruction requiring laparotomy and small bowel resection). CONCLUSIONS: Robotic augmentation ileo-cystoplasty can provide significant symptom relief for patients with a small contracted bladder. Both anterior and posterior approaches of robotic augmentation ileo-cystoplasty did not show any difference in the improvement in functional bladder capacity after the operation. Source of Funding: Nil © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e748 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chi Hang Yee More articles by this author Phoebe Cl Lam More articles by this author Yuek Lam Hong More articles by this author Pui Tak Lai More articles by this author Yuk Him Tam More articles by this author Timothy Chang Kidd Ng More articles by this author Steffi Kar Kei Yuen More articles by this author Mandy Ho Man Tam More articles by this author Chi Kwok Chan More articles by this author Ka Lun Lo More articles by this author Jeremy Yuen Chun Teoh More articles by this author Peter Ka Fung Chiu More articles by this author Chi Fai Ng More articles by this author Expand All Advertisement PDF downloadLoading ...

PD35-04 OPEN VS. ROBOTIC-ASSISTED RECONSTRUCTION IN VESICOURETHRAL ANASTOMOTIC STENOSIS

You have accessJournal of UrologyCME1 Apr 2023PD35-04 OPEN VS. ROBOTIC-ASSISTED RECONSTRUCTION IN VESICOURETHRAL ANASTOMOTIC STENOSIS Metin Savun, Harun Ozdemir, Emin Taha Keskin, Yunus Colakoglu, Halil Lutfi Canat, and Abdulmuttalip Simsek Metin SavunMetin Savun More articles by this author , Harun OzdemirHarun Ozdemir More articles by this author , Emin Taha KeskinEmin Taha Keskin More articles by this author , Yunus ColakogluYunus Colakoglu More articles by this author , Halil Lutfi CanatHalil Lutfi Canat More articles by this author , and Abdulmuttalip SimsekAbdulmuttalip Simsek More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003333.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Vesicourethral anastomotic stenosis (VUAS) that is unresponsive to endoscopic treatment after radical prostatectomy can be treated with open or robot-assisted reconstruction. In this study, we aimed to compare the patency and complications of these two methods. METHODS: Eighteen patients who underwent open perineal reconstruction surgery and ten patients who underwent robot-assisted (Da Vinci XI) transabdominal reconstruction surgery for VUAS between July 2017 and August 2022 were included in this study. Demographic, operative, and postoperative patient data were examined. The two methods were compared in terms of patency, complications, recurrence, and incontinence. Patency was defined as either the passage of a 16 French cystoscope or a maximum flow on uroflowmetry of >15 ml/s. Incontinence was defined as use of more than one pad per day. RESULTS: The median age was 67 years, and the number of previous endoscopic interventions was seven in both groups. The median operation time was 120 and 150 minutes (p:0.175), median bleeding amount was 200 and 100 ml (p:0,001), and median hospitalization time was four and three days (0,001) in the open and robotic-asisted groups, respectively. Wound infection (Clavien grade 2) developed in one patient and puborectal fistula (Clavien grade 3b) developed in one patient in the open group. Wound infection (Clavien grade 2) developed in one patient and ileus (Clavien grade 2) developed in one patient in the robotic-asisted group (p:0,724). Patency rate is 77.8% and 80.0% (p:0,944) in the open and robotic-asisted groups, respectively. All patients (%100) in the open group experienced incontinence during the follow-up period. Of the six patients without pre-existing incontinence, five (16,6%) remained continent at the last follow-up in the robotic-asisted groups. CONCLUSIONS: Compared to open perineal reconstruction, robot-assisted transabdominal VUAS reconstruction has less bleeding and a shorter hospitalization time. Although the patency and complication rates of both methods are similar, robot-assisted reconstruction is superior in terms of continence rates. Source of Funding: There is no source of fundings © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e975 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Metin Savun More articles by this author Harun Ozdemir More articles by this author Emin Taha Keskin More articles by this author Yunus Colakoglu More articles by this author Halil Lutfi Canat More articles by this author Abdulmuttalip Simsek More articles by this author Expand All Advertisement PDF downloadLoading ...

Assessing Obstetric Anal Sphincter Injuries: A Comparison of Exoanal and Endoanal Ultrasound.

To explore the differences in assessing obstetric anal sphincter injuries (OASI) between transperineal ultrasound (TPUS) and endoanal ultrasound (EAUS) and test relationships between ultrasound findings and anal incontinence (AI) symptoms. A group of 196 women with a history of vaginal delivery was recruited. OASI was detected in a set of 5 slices by EAUS and 8 slices by TPUS. OASI grading was performed on TPUS rules and EAUS rules. A "significant sphincter defect" was diagnosed by TPUS and EAUS using "2/3 rules." Symptoms of AI were determined using the St Mark's Incontinence Score (SMIS). Ultrasound findings were compared between the two methods and correlated with symptoms. Of 196 women, 29 (14.8%) suffered from AI with a mean SMIS of 12.1 ± 4.5, and 70 (35.7%) women with a mean age of 57 years had suspected OASI on imaging. Twenty-one (10.7%) "significant defects" were diagnosed by TPUS and 24 (12.2%) by EAUS. OASI Grades on TPUS had good agreement with EAUS rules (k=0.70, P < .001). Logistic regression analysis showed that OASI Grade on imaging and "significant sphincter defects" seen on both forms of imaging were associated with AI symptoms. The odds ratio was 46 and 38 for "significant defects" on TPUS and EAUS, and 14 and 7 for OASI 3b+ on TPUS and EAUS in predicting AI, respectively. "Significant defects" diagnosed by EAUS or TPUS and OASI Grade 3b+ predict AI symptoms. The diagnostic performance of endoanal and exoanal ultrasound (EAUS and TPUS) appear to be very similar.

Clavien-Dindo, comprehensive complication index and classification of intraoperative adverse events: a uniform and holistic approach in adverse event registration for (deep) endometriosis surgery.

What is the additional value of the comprehensive complication index (CCI) and ClassIntra system (classification for intraoperative adverse events (ioAEs)) in adverse event (AE) reporting in (deep) endometriosis (DE) surgery compared to only using the Clavien-Dindo (CD) system? The CCI and ClassIntra are useful additional tools alongside the CD system for a complete and uniform overview of the total AE burden in patients with extensive surgery (such as DE), and with this uniform data registration, it is possible to provide greater insight into the quality of care. Uniform comparison of AEs reported in the literature is hampered by scattered registration. In endometriosis surgery, the usage of the CD complication system and the CCI is internationally recommended; however, the CCI is not routinely adapted in endometriosis care and research. Furthermore, a recommendation for ioAEs registration in endometriosis surgery is lacking, although this is vital information in surgical quality assessments. A prospective mono-center study was conducted with 870 surgical DE cases from a non-university DE expertise center between February 2019 and December 2021. Endometriosis cases were collected with the EQUSUM system, a publicly available web-based application for registration of surgical procedures for endometriosis. Postoperative adverse events (poAEs) were classified with the CD complication system and CCI. Differences in reporting and classifying AEs between the CCI and the CD were assessed. ioAEs were assessed with the ClassIntra. The primary outcome measure was to assess the additional value toward the CD classification with the introduction of the CCI and ClassIntra. In addition, we report a benchmark for the CCI in DE surgery. A total of 870 DE procedures were registered, of which 145 procedures with one or more poAEs, resulting in a poAE rate of 16.7% (145/870), of which in 36 cases (4.1%), the poAE was classified as severe (≥Grade 3b). The median CCI (interquartile range) of patients with poAEs was 20.9 (20.9-31.7) and 33.7 (33.7-39.7) in the group of patients with severe poAEs. In 20 patients (13.8%), the CCI was higher than the CD because of multiple poAEs. There were 11 ioAEs reported (11/870, 1.3%) in all procedures, mostly minor and directly repaired serosa injuries. This study was conducted at a single center; thus, trends in AE rates and type of AEs could differ from other centers. Furthermore, no conclusion could be drawn on ioAEs in relation to the postoperative course because the power of this database is not robust enough for that purpose. From our data, we would advise to use the Clavien-Dindo classification system together with the CCI and ClassIntra for a complete overview of AE registration. The CCI appeared to provide a more complete overview of the total burden of poAEs compared to only reporting the most severe poAEs (as with CD). If the use of the CD, CCI, and ClassIntra is widely adapted, uniform data comparison will be possible at (inter)national level, providing better insight into the quality of care. Our data could be used as a first benchmark for other DE centers to optimize information provision in the shared decision-making process. No funding was received for this study. The authors have no conflicts of interest to declare. N/A.

Feasibility and Safety of Laparoscopic D2 Gastrectomy in Combination with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Gastric Cancer at High Risk of Recurrence-The PIPAC-OPC4 Study.

Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m2) and doxorubicin (2.1 mg/m2) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy. Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy. Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe.

Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance.

Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between 'lowgrade' (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups; G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of the G3BFL cases. With a median of 5 years follow-up, the overall survival and progression-free survival of G3BFL patients was better than that of DLBCL patients (P<0.001 and P<0.001, respectively); however, G3BFL patients were younger (P<0.001) with better performance status (P<0.001), less extranodal disease (P<0.001) and more frequently had normal lactate dehydrogenase (P<0.001) at baseline. The overall and progression-free survival of patients with G3BFL and G3AFL were similar (P=0.83 and P=0.80, respectively). After frontline immunochemotherapy, 24% of G3BFL relapsed; relapse rates were 63% in the DLBCL cohort and 19% in the low-grade FL cohort. Eight percent of relapses occurred beyond 5 years. In this G3BFL cohort, the revised International Prognostic Index successfully delineated risk groups, but the Follicular Lymphoma International Prognostic Index did not. We conclude that patients with immunochemotherapy-treated G3BFL have similar survival outcomes to those with G3AFL, yet a favorable baseline profile and distinctly superior prognosis compared to patients with DLBCL.

Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database.

Bendamustine has a potent immunosuppressive effect because it causes T-cell lymphopenia, which might lead to a second primary malignancy (SPM) and would increase the risk of infection. Using the Medical Data Vision administrative claims database, we compared the cumulative incidence of SPM, infections within 6months, and overall survival (OS) among untreated patients with indolent B-cell lymphomas (iBCL) who received rituximab-based chemotherapy between 2009 and 2020. Patients with grade 3b follicular lymphoma or a previous history of malignancy were excluded. Eligible 5234 patients were assigned to three cohorts: rituximab monotherapy (N=780), RCHOP/RCVP/RTHPCOP (doxorubicin replaced with pirarubicin) (N=2298), or bendamustine/rituximab (BR) (N=2156). There were 589 recorded SPMs, of which myelodysplastic syndromes were the most common (1.7%). The cumulative incidence of SPM was significantly higher in patients treated with BR than in those treated with rituximab monotherapy (p<0.01) or RCHOP/RCVP/RTHPCOP (p<0.0001): the 5-year cumulative incidence function was 18.1%, 12.5%, and 12.9%, respectively. In the Fine-Gray subdistribution hazards model, BR showed a significantly higher cumulative incidence of SPM than RCHOP/RCVP/RTHPCOP (subhazard ratio, 1.33; 95% confidence interval [CI], 1.10-1.61). Furthermore, in sensitivity analysis, a nested case-control study using an entire cohort showed consistent results: the SPM odds ratios (95% CI) of first-line bendamustine, bendamustine after first-line, and any-line bendamustine were 1.43 (1.14-1.78), 1.26 (0.96-1.64), and 1.33 (1.09-1.62), respectively. Regarding infections, adjusted odds ratios (95% CI) of BR compared to RCHOP/RCVP/RTHPCOP were as follows: cytomegalovirus infection, 13.7 (4.88-38.4); bacterial pneumonia, 0.63 (0.50-0.78); and pneumocystis pneumonia, 0.24 (0.11-0.53). There was no significant difference in OS between RCHOP/RCVP/RTHPCOP and BR in patients with follicular, mantle cell, marginal zone, or lymphoplasmacytic lymphomas. In conclusion, treatment strategies that consider the risk of SPM and infections after chemotherapy are warranted in patients with iBCL.