Require Salvage Therapy Research Articles

P0513 Comparative Evaluation of Clinical Scores for Predicting Response to Systemic Steroid Treatment in Hospitalized Adult Patients with Acute Severe Ulcerative Colitis: A Retrospective Study

Abstract Background Approximately 30% of hospitalized patients with acute severe ulcerative colitis (ASUC) may be refractory to systemic glucocorticoid (GC) therapy, administered orally or intravenously necessitating salvage therapy 1. Clinical tools predicting response to GC could allow for early initiation of salvage therapy thus reducing GC exposure and improving overall outcomes. However, comparative studies for available prognostic scores are limited and yield conflicting results 2,3. We aimed to determine the best performing score on a cohort of patients with ASUC from a large tertiary hospital. Methods A retrospective cohort study was conducted between 2017-2022. Hospitalized patients with ASUC, as defined by Truelove and Witts criteria and treated with GC, were included. Patients were classified as GC-refractory (GC-Ref) if they had no clinical and biochemical response, requiring salvage therapy. Assessments for GC response were performed on the third and seventh day of hospitalization. The predictive value of the Mayo endoscopic and Adams scores was evaluated on admission, while the Gibson, Ho, Lindgren, and Oxford scores were assessed on the third day. We compared scores using a multivariate logistic regression and ROC analysis. Results Ninety-six patients met the inclusion criteria and were included, 56 (58%) were GC-responsive (GC-Res) and 40 (42%) were GC-Ref. The mean age of admission was similar between the groups (GC-Res: 42.2 ± 16.7 years; GC-Ref: 37.15 ± 15.3; P=0.1). The GC-Ref group had more extensive disease (65% Vs 38.2%, P=0.01), (Table 1). On admission, the GC-Ref group had significantly more bowel movements per day (14.6 Vs 11.3, P=0.05), elevated CRP levels (91.5 mg/L Vs 58.4 mg/L, P=0.005), higher MAYO score (2.8 Vs 2.3, P=0.028) and lower albumin levels (32 g/L Vs 35.4 g/L, P=0.008) and body mass index (20.3 kg/m2 Vs 23.8 kg/m2, P=0.02). The Gibson score (based on three or more stools per day and a CRP-to-albumin ratio (CAR) above 0.85) and Mayo Endoscopic Score demonstrated appropriate sensitivity and significant predictive value for identifying refractory patients (aOR: 11.3 (95% CI 1.87-68), P=0.008 and aOR: 7.9 (95%CI 1.8-34), P=0.006); respectively. The Gibson score, showed the best overall performance with a sensitivity of 0.7, specificity of 0.75 and positive predictive value of 0.71 (Table 2). Of the individual elements of the various scores, CAR measured on the third day of hospitalization had the highest predictive value (aOR: 12.9 (95% CI 2.5-67), P=0.002) with sensitivity of 0.72, and specificity of 0.65. Conclusion In our cohort, the Gibson score proved to be the most effective predictive tool for identifying patients with steroid refractory ASUC. This need to be confirmed in larger prospective cohorts.

P1049 Intestinal ultrasound for assessment of steroid-refractory disease in patients hospitalized due to Acute Severe Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition. Intravenous corticosteroids are recommended as the initial treatment for adult patients with ASUC. However, one-third of patients with ASUC are steroid-refractory and will require medical salvage therapy or surgery. Timely identification of patients who will not adequately respond to steroid treatment is crucial. This study aimed to evaluate whether intestinal ultrasound (IUS), could potentially be of additional value in predicting inadequate response to IV steroids in patients admitted with ASUC. Methods A retrospective cohort study was conducted including all patients with ASUC admitted between 1/2018-12/2023 to a large tertiary referral center (Rabin Medical Center) in Israel. All patients who had laboratory tests, sigmoidoscopy and IUS were included. We used inflammatory markers, Milan Ultrasound Criteria (MUC) and Mayo endoscopic score (EMS) to assess disease activity. The need for in hospital salvage therapy (infliximab or cyclosporine) was detected. Results Out of 158 patients with ASUC admitted during the study period, baseline IUS was available in 43. Medical salvage therapy was required in 19 (44%): infliximab n=13, cyclosporine n=6. Patients ultimately requiring salvage therapy during their hospitalization had significantly worse laboratory baseline disease activity parameters. Specifically, median albumin, hemoglobin and c-reactive protein were 2.5 vs. 3.7 g/dl; 8.9 vs 11.9 g/dl; and 10.2 vs. 6.8 mg/dl in the salvage therapy group vs. steroid therapy only group, respectively (p<0.05). An EMS of 3 was detected in 14/19 (74%) of patients requiring medical salvage therapy compared to 14/24 (58%) in the steroid therapy only group. Finally, bowel wall thickness (BWT) and MUC of the sigmoid colon in the medical salvage therapy group was 5.1, 9 compared to 4.9, 8.5 in the steroid therapy only group (p>0.05). Conclusion In patients hospitalized with ASUC, laboratory values were significantly worse in patients ultimately needing salvage therapy. IUS measurements were not significantly different between these two groups. In this sick subgroup of patients with ASUC, IUS was not able to provide additional information regarding the risk of steroid failure. Defining specific cutoffs in larger studies may contribute to early non-invasive risk-stratification.

Predictors of salvage therapy for parasagittal meningiomas treated with primary surgery, radiosurgery, or surgery plus adjuvant radiotherapy

ObjectiveParasagittal meningiomas (PM) are treated with primary microsurgery, radiosurgery (SRS), or surgery with adjuvant radiation. We investigated predictors of tumor progression requiring salvage surgery or radiation treatment. We sought to determine whether primary treatment modality, or radiologic, histologic, and clinical variables were associated with tumor progression requiring salvage treatment. MethodsRetrospective study of 109 consecutive patients with PMs treated with primary surgery, radiation (RT), or surgery plus adjuvant RT (2000–2017) and minimum 5 years follow-up. Patient, radiologic, histologic, and treatment data were analyzed using standard statistical methods. ResultsMedian follow up was 8.5 years. Primary treatment for PM was surgery in 76 patients, radiation in 16 patients, and surgery plus adjuvant radiation in 17 patients. Forty percent of parasagittal meningiomas in our cohort required some form of salvage treatment. On univariate analysis, brain invasion (OR: 6.93, p < 0.01), WHO grade 2/3 (OR: 4.54, p < 0.01), peritumoral edema (OR: 2.81, p = 0.01), sagittal sinus invasion (OR: 6.36, p < 0.01), sagittal sinus occlusion (OR: 4.86, p < 0.01), and non-spherical shape (OR: 3.89, p < 0.01) were significantly associated with receiving salvage treatment. On multivariate analysis, superior sagittal sinus invasion (OR: 8.22, p = 0.01) and WHO grade 2&3 (OR: 7.58, p < 0.01) were independently associated with receiving salvage treatment. There was no difference in time to salvage therapy (p = 0.11) or time to progression (p = 0.43) between patients receiving primary surgery alone, RT alone, or surgery plus adjuvant RT. Patients who had initial surgery were more likely to have peritumoral edema on preoperative imaging (p = 0.01). Median tumor volume was 19.0 cm3 in patients receiving primary surgery, 5.3 cm3 for RT, and 24.4 cm3 for surgery plus adjuvant RT (p < 0.01). ConclusionSuperior sagittal sinus invasion and WHO grade 2/3 are independently associated with PM progression requiring salvage therapy regardless of extent of resection or primary treatment modality. Parasagittal meningiomas have a high rate of recurrence with 80.0% of patients with WHO grade 2/3 tumors with sinus invasion requiring salvage treatment whereas only 13.6% of the WHO grade 1 tumors without sinus invasion required salvage treatment. This information is useful when counseling patients about disease management and setting expectations.

Avatrombopag in Immune Thrombocytopenia (ITP). Real-Life Experience of Its Use in Hospitals within the Community of Madrid, Spain (AVAMAD STUDY)

Introduction Thrombopoietin receptor agonists (TPO-RAs) are recommended as second-line treatment for immune thrombocytopenia (ITP) according to the Spanish ITP group (GEPTI) guidelines. Avatrombopag (AVA) is an oral TPO-RA, recently launched in Spain, for which we have little data available beyond the pivotal trial. The main objectives of our study were to evaluate the efficacy and safety of AVA in patients with ITP. Methods In this observational, retrospective, multicenter study in 10 hospitals in the Community of Madrid, we have analyzed adult patients with ITP treated with AVA from July 2022-May 2023. Demographic characteristics, response, rescue therapy, adverse effects and treatment discontinuation were analyzed. The definition of ITP and response were those described by Provan et al. The study protocol was designed and applied in accordance with the principles of the Declaration of Helsinki. Statistical analysis was performed using IBM SPSS Statistics v28.0. Fisher and Mann-Whitney tests were used for bivariate analysis and Kaplan-Meier curves for response time. Results A total of 66 patients were included. The median age was 52 years old (IQR 34-71). Table 1 describes the general characteristics. There was a median of 2 (IQR1-3) previous lines of treatment before starting AVA. The reasons for its initiation were: refractoriness to previous treatment and/or corticodependence in 39% (25/66), loss of response in 34% (22/66), switch due to patient preference in 14% (9/66) and switch due to adverse effects with previous treatment in 5% (3/66). In 8% (5/66) there was more than one reason for change. The previous line of treatment is described in Table 1. The median platelet count at baseline was 36x10 9/L(IQR 13-61). With a median follow-up of 16 weeks (IQR 8-28), 86% of the pateints (57/66) were responders. 73% had complete response. 24% percent (16/66) required salvage therapy. In the bivariate analysis, 100% of those aged ≥65 years presented response vs. 75% in &amp;lt;65 years (p=0.003). A complete response was achieved in 88.6% of women versus 54.8% of men (p=0.002). Patients with complete response received fewer lines of treatment (1 [IQR 1-3] vs 3.5 [IQR 2-6]); p&amp;lt; 0.001). Complete response was achieved in 60.5% of patients who received previous treatment with eltrombopag (p=0.01), in 47.8% of those with romiplostim (p&amp;lt;0.001), in 40% with rituximab (p=0.02), in 33.3% with splenectomy (p=.0.01) and in 22.2% with fostamatinib (p=0.00).The median time from initiation of AVA to response was 2,1 weeks [IQR 2-4] (Figure 1). Twelve patients (18%) discontinued AVA due to: lack of response (n=6), adverse effects (n=3), one patient prior to scheduled surgery, and In these patients AVA was restarted with dose adjustment. Adverse effects are described in Table 1. Conclusions The results of the use of AVA in real-life demonstrated a high response rate, more favorable in the initial lines of treatment. In addition, it reduces the need for salvage therapy and has a low adverse effect profile. A larger number of patients and a longer follow-up are needed to verify these results and to answer some questions such as whether it is possible to discontinue AVA treatment after response and the percentage of patients with sustained response following AVA discontinuation.

End-of-Treatment Response Assessment after Frontline Therapy for Aggressive B-Cell Lymphoma: Landmark Comparison of a Singular PET/CT Scan Versus Ultrasensitive Circulating Tumor DNA

Background : Lymphoma response criteria rely on PET/CT scans at end of therapy (EOT) to determine complete response (CR), which is necessary for cure. ~25% of patients achieve &amp;lt;CR by response criteria, but PET/CT scans have imperfect specificity and the positive predictive value of a single PET/CT scan at EOT is only ~50% (Kostakoglu 2021). To overcome this limitation, clinicians use additional tests including tissue biopsies or repeat PET/CT scans prior to salvage therapy to adjudicate positive results, but it remains unclear how often this occurs. Circulating tumor DNA (ctDNA) has improved tumor specificity that may reduce reliance on additional tests. We addressed these questions within a clinical trial delivering 1L therapy to pts with aggressive B-cell lymphoma. Methods : Pts were enrolled in a phase 2 study of DA-EPOCH-R or R-CHOP +/- acalabrutinib for treatment naïve DLBCL or high-grade B-cell lymphoma (HGBCL) [NCT04002947]. All pts were &amp;gt;18yrs old, stage II-IV, with adequate organ function. Pts completing induction therapy with available EOT PET/CT scans and EOT plasma samples were studied. PET/CT scans were interpreted by 2 nuclear medicine (NM) radiologists blinded to clinical outcomes using the 5-point Deauville Score (DS) with DS4/5 considered positive. Tissue biopsies and unplanned PET scans after the EOT PET/CT scan to determine remission status were recorded. Measurable residual disease (MRD) in plasma cfDNA was evaluated by Phased Variant Enrichment &amp; Detection Sequencing (PhasED-Seq) at Foresight Diagnostics blinded to clinical outcomes. Tumor derived Phased Variants (PVs) were identified from baseline pretreatment plasma samples or baseline tumor tissue, with matched constitutional DNA from paired PBMCs used to censor germline variants and CHIP. PVs were used to assess EOT MRD. Results were reported as MRD positive when ctDNA levels exceeded an analytical detection threshold (~1:10 6 cfDNA molecules) corresponding to 98% specificity. The prognostic utility of MRD was compared to standardized PET/CT scan at EOT to freedom-from-progression (FFP) and progression-free survival (PFS). Results : 55 enrolled pts completing planned therapy had EOT PET/CT and MRD analyzed. 54 (98%) pts were successfully genotyped and comprised the study population. Median age was 61 (range 26-85), including 22 (41%) female, 44 (81%) with advanced stage, and 26 (48%) with IPI score ³3. Pathologic subtypes included 24 (44%) GCB, 21 (39%) non-GCB, 8 (15%) HGBL-DH, and 1 (2%) THRLBCL. 43 (80%) pts received DA-EPOCH-R and 11 (20%) pts received R-CHOP. Twenty-six (48%) pts received acalabrutinib with R-chemotherapy. After 26 months median follow-up, the 2-year FFP and PFS of the cohort was 89% and 84%. Fourteen (26%) pts had a positive EOT PET/CT scan and 40 (74%) were negative. The concordance rate between the 2 NM radiologists on positive scans was 100%. Only 2 of 14 patients with a positive EOT PET/CT had clinical progression requiring salvage therapy (14% PPV). Nine (64%) of these pts required additional tests to determine remission status including 5 repeat PET/CT scans and 4 tissue biopsies. The 2-year PFS for pts with a positive vs negative EOT PET/CT was 66% vs 90% (p=0.08, Fig.A). Twelve (22%) pts had detectable EOT MRD and 42 (78%) were undetectable. 7 pts with detectable EOT MRD had clinical progression requiring salvage therapy or have died. While no pt with undetectable EOT MRD progressed, 1 (2%) died in remission of sudden cardiac death. Of 14 pts with positive EOT PET/CT, 7 (50%) had undetectable ctDNA and none progressed, suggesting MRD testing could have potentially rendered additional tests unnecessary. Conversely, patients with positive PET/CTs who progressed invariably had detectable ctDNA at EOT, suggesting utility of MRD for adjudicating PET/CT results. The 2-yr PFS for pts with detectable vs undetectable EOT MRD was 33% vs 98% (p&amp;lt;0.0001, Fig.B). At EOT, the PFS hazard ratio for MRD was 35.7, as compared with 3.1 for PET/CT. Conclusions : Response evaluations relying on PET/CT scans often require additional tests and procedures to assess remission status in aggressive B-cell lymphomas. Initiation of salvage therapy without adjudication in patients not achieving CR by EOT PET/CT scans will result in overtreatment. Given the higher specificity and PPV of EOT MRD, we propose an integrated response evaluation strategy combining these methods to reduce unnecessary additional tests and overtreatment.

Long-term outcomes of PD-1 blockade in metastatic or unresectable cutaneous squamous cell cancer.

e21551 Background: Cutaneous squamous cell carcinoma (CSCC) is the 2nd most common malignancy in the US. Approximately 10% of patients will experience either recurrent or metastatic disease, leading to worsened morbidity and mortality. In 2019, anti-PD1 therapy was FDA approved for metastatic or unresectable CSCC, and has been established as the standard frontline systemic therapy for this disease. Here we present our long-term, follow-up data investigating the efficacy, safety, and durability of PD-1 therapy for CSCC. Methods: This is a retrospective cohort study of metastatic or unresectable CSCC patients treated with PD-1 therapy at the University of Southern California Norris Comprehensive Cancer Center and the Scripps MD Anderson Cancer Center between June 2016 and January 2023. Patient demographics, tumor characteristics, and treatment related variables were collected. Objective response (ORR) was collected per RECIST criteria. Kaplan-Meier curves were used to estimate progression free survival (PFS) and overall survival (OS). For patients receiving salvage therapy post-PD1, progression free survival 2 (PFS2) and objective response rate 2 (ORR2) were also calculated. Toxicities were graded per CTCAE v5.0. Results: A total of 39 patients diagnosed with CSCC received at least one cycle of PD-1 therapy; among these 8 were excluded from efficacy analysis. Patients were on average 68 years old (range 22-97), predominantly male (69.2%) and Caucasian (74.4%). The most common primary tumor location was head/neck (64.1%), followed by extremity (15.4%). The mean tumor diameter was 6.0 cm (4.5-7.5, 95% CI). The majority of tumors were either moderately (33.3%) or poorly (28.2%) differentiated. The most common sites of metastatic disease included lymph node (41.0%), skin/soft tissue (33.3%) and bone (25.6%). Patients received on average 7 cycles of PD-1 therapy (range 1-26) and were followed for median 13.8 months. ORR for all patients was 39.0%, including CR and PR in 7 (22.6%) and 4 (13.0%) patients, respectively; 10 patients (32.2%) achieved stable disease (SD), while 7 patients (22.6%) had progression of disease (PD). Median PFS was 6.8 months, while OS was 26.7 months. Among 10 patients receiving salvage therapy after PD-1, 6 (60.0%) received a platinum-containing regimen. Median PFS2 was 4.4 months, while ORR2 was 10.0% with 1 PR, 4 SD, and 5 with PD. PD-1 therapy was well tolerated with 13 patients (33.3%) experiencing Grade 1-2 toxicity and 2 patients (5.2%) experiencing Grade 3-4. Conclusions: In this study of long-term outcomes of CSCC patients treated with PD-1 blockade, we found that initial responses to PD-1 therapy were durable, although PFS2 was less durable for patients who required salvage therapy and ORR2 was low. Novel treatment options are needed for patients with advanced CSCC who do not achieve durable responses to PD-1 based therapy.

Therapeutic Drug Monitoring of Infliximab in Acute Severe Ulcerative Colitis.

Therapeutic drug monitoring (TDM) is a useful strategy in ulcerative colitis (UC). Nearly a quarter of UC patients will experience acute severe UC (ASUC) in their lifetime, including 30% who will fail first-line corticosteroid therapy. Steroid-refractory ASUC patients require salvage therapy with infliximab, cyclosporine, or colectomy. Fewer data are available for the use of TDM of infliximab in ASUC. The pharmacokinetics of ASUC make TDM in this population more complex. High inflammatory burden is associated with increased infliximab clearance, which is associated with lower infliximab drug concentrations. Observational data support the association between increased serum infliximab concentrations, lower clearance, and favorable clinical and endoscopic outcomes, as well as decreased rates of colectomy. Data regarding the benefit of accelerated or intensified dosing strategies of infliximab-as well as target drug concentration thresholds-in ASUC patients remain more equivocal, though limited by their observational nature. Studies are underway to further evaluate optimal dosing and TDM targets in this population. This review examines the evidence for TDM in patients with ASUC, with a focus on infliximab.

Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation

BackgroundAlthough most patients with diffuse large B-cell lymphoma (DLBCL) achieve complete remission after first-line rituximab-containing immunochemotherapy, up to 40% of patients relapse and require salvage therapy. Among those patients, a substantial proportion remain refractory to salvage therapy due to insufficient efficacy or intolerance of toxicities. A hypomethylating agent, 5-azacytidine, showed a chemosensitizing effect when primed before chemotherapy in lymphoma cell lines and newly diagnosed DLBCL patients. However, its potential to improve outcomes of salvage chemotherapy in DLBCL has not been investigated.ResultsIn this study, we demonstrated the mechanism of 5-azacytidine priming as a chemosensitizer in a platinum-based salvage regimen. This chemosensitizing effect was associated with endogenous retrovirus (ERV)-induced viral mimicry responses via the cGAS-STING axis. We found deficiency of cGAS impaired the chemosensitizing effect of 5-azacytidine. Furthermore, combining vitamin C and 5-azacytidine to synergistically activate STING could be a potential remedy for insufficient priming induced by 5-azacytidine alone.ConclusionsTaken together, the chemosensitizing effect of 5-azacytidine could be exploited to overcome the limitations of the current platinum-containing salvage chemotherapy in DLBCL and the status of cGAS-STING has the potential to predict the efficacy of 5-azacytidine priming.

Radiation-Induced Sarcomas of the Breast: A Review of a 20-Year Single-Center Experience.

Background Radiation-induced sarcomas (RISs) are histologically proven sarcomas within or around a previously irradiated site, per Cahan's criteria. RIS incidence is higher in breast cancer compared to other solid cancers and the prognosis remains poor given limited treatment options. This study aimed to review 20-year experience with RISs at a large tertiary care center. Methodology Using our institutional cancer registry database, we included patients meeting Cahan's criteria diagnosed between 2000 and 2020. Patient demographics, oncologic treatment, and oncologic outcomes data were collected. Descriptive statistics were used to describe demographic data. Oncologic outcomes were assessed using the Kaplan-Meier method. Results A total of 19 patients were identified. The median age at RIS diagnosis was 72 years (range = 39-82 months), and the median latency period for the development of RIS was 112 months (range = 53-300 months). All patients underwent surgery, three patients received systemic therapy, and six patients received re-irradiation as salvage treatment. The median follow-up time was 31 months (range = 6-172 months) from the diagnosis of RIS. Overall, five patients had local recurrence, and one patient developed distant metastases. The median time to progression was seven months (range = 4-14 months). The progression-free survival (95% confidence interval (CI)) at two years was 56.1% (37.4-84.4%). At follow-up two years after the diagnosis of sarcoma, the overall survival (95% CI) was 88.9% (75.5-100%). Conclusions While breast RIS remains rare, when managed in a large tertiary care center, overall survival outcomes appear favorable. A significant proportion of patients recur locally after maximal treatment and require salvage therapy to improve outcomes. These patients should be managed in high-volume centers where multidisciplinary expertise is available.

Anti-PD-1 therapy can possibly reverse CAR T cells exhaustion in DLBCL.

Exhaustion describes a condition in which T cells are unable to perform any function. It has been characterized by chronic infections and cancers.1 Various features within the tumour microenvironment led to dysfunction of T infiltrating lymphocytes, such as antigen persistence, nutrient deprivation and/or PDCD1 demethylation.2 This gene codes for the protein PD-1, whose expression is the most known feature of exhaustion. Targeting PD-1 with nivolumab or pembrolizumab led to impressive clinical success in the context of various metastatic tumours and Hodgkin lymphoma.3 Even though single-agent anti-PD1 showed low and transient antitumor activity in R/R DLBCL,4 with the exception of patients with HIV-related lymphoma, that may benefit of a long-term disease control.5 About 60 per cent of patients treated with axicabtagene ciloleucel for a relapsing or refractory diffuse large B cell lymphoma (R/R DLBCL) do not achieve a persistent response.6 Massive research effort has been undertaken to dissect CAR T cell failure. Among other causes, absence/low expansion, functionality or persistence of those engineered T cells had been related to exhaustion features. These characteristics have been described among harvested T cells, CAR T cells from the final product and/or circulating CAR T cells, themselves linked to tumour burden, tumour microenvironment and/or systemic inflammation.7 In this issue, Gazeau et al. report on their experience with nivolumab in that context. With that drug, they have been trying to rescue 11 patients that did not achieve a complete remission 30 days after axicabtagene ciloleucel for a R/R DLBCL. They treated patients in 3 different situations. The “primary refractory” group included patients who showed stable or progressive disease at initial evaluation, the “booster” group included patients who achieved a partial response and were belief to require additional therapy, and the “salvage” group included patients who progressed after achieving a partial response and therefore required salvage therapy. Nivolumab was administrated every 2 weeks, and efficacy was evaluated by PET/CT after four injections. Regarding safety, four mild respiratory tract infections were reported, and no CRS/ICANS was observed. Four patients achieved a complete response after 2 months of treatment, two patients were in the situation of partial response at D30 and two others were experiencing relapsing disease after a partial response. A second expansion of circulating CAR T cells was observed, after a single injection of nivolumab, which argues on reversion of CAR T cell exhaustion: Cmax was 0.035 G/L, lower that the initial expansion but following a long period when the CAR T cells were undetectable. Moreover, the secretion of pro-inflammatory cytokines is probably reflecting the functionality of those CAR T cells. Another group recently reported three patients with early progression or relapse, after being treated with 4-1BB costimulated CD19 CAR T cells, who responded to pembrolizumab.8 Ten out of the 12 patients treated in this study experienced a second expansion of circulating CAR T cell. Interestingly, pretreatment biopsy from seven out of nine patients had positive PD1 ligand expression (PD-L1). Other groups described that PD-L1 expression by DLBCL tumour cells is associated with activated B cell genotype, as well as poor outcomes.9 Taken together, those clinical data suggest a potential therapeutic benefit of the reversion of CAR T cell exhaustion with anti-PD-1 therapy. Ongoing clinical trials will help to determine the best candidates and modalities for such salvage.

MP73-02 FOCAL THERAPY - 7 YEARS EXPERIENCE WITH FOCAL HIGH INTENSITY FOCUSED ULTRASOUND IN 164 PATIENTS WITH PROSTATE CANCER: SINGLE CENTER RESULTS

You have accessJournal of UrologyCME1 Apr 2023MP73-02 FOCAL THERAPY - 7 YEARS EXPERIENCE WITH FOCAL HIGH INTENSITY FOCUSED ULTRASOUND IN 164 PATIENTS WITH PROSTATE CANCER: SINGLE CENTER RESULTS Yamini Nagaraj, Fabian Falkenbach, Valia Veleva, Randi Marisa Pose, Jonas Ekrutt, Raisa Abrams-Pompe, Jaideep Ratkal, Pierre Tennstedt, Derya Tilki, Hans Heinzer, Markus Graefen, and Georg Salomon Yamini NagarajYamini Nagaraj More articles by this author , Fabian FalkenbachFabian Falkenbach More articles by this author , Valia VelevaValia Veleva More articles by this author , Randi Marisa PoseRandi Marisa Pose More articles by this author , Jonas EkruttJonas Ekrutt More articles by this author , Raisa Abrams-PompeRaisa Abrams-Pompe More articles by this author , Jaideep RatkalJaideep Ratkal More articles by this author , Pierre TennstedtPierre Tennstedt More articles by this author , Derya TilkiDerya Tilki More articles by this author , Hans HeinzerHans Heinzer More articles by this author , Markus GraefenMarkus Graefen More articles by this author , and Georg SalomonGeorg Salomon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy aims to selectively ablate tumor lesions and preserve prostate tissue, thus minimizing side effect whilst providing oncological control. The experience of the first 2 years lead to improved diagnostic work up prior to HIFU with better patient selection and less tumor recurrence in the following 5 years. The strong recommendation of control biopsy in the follow up, lead to a reliable and early selection of patients requiring salvage therapy and thus improving oncological results. METHODS: This is a prospective evaluation of 164 patients undergoing focal high intensity focused ultrasound (HIFU) in our institution from July 2015 till June 2022. Patients were required to have a unilateral Gleason score (GS) ≤7, stage T1 or T2 and a PSA level of≤15 ng/ml. Tumor localization was done using multiparametric MRI followed by mainly transrectal targeted and systematic biopsies of any lesion PI-RADS≥3. Systematic biopsy was recommended 1 year after HIFU with PSA levels every 3 months. An MRI was scheduled at 3 years post HIFU. In the control biopsy significant cancer recurrence was defined as >3mm GS 3+3, >3 positive cores or any GS≥3+4; these patients were offered further treatment; either a repeat HIFU, radical prostatectomy (RP) or radiation therapy (RT). Urinary and erectile function were assessed using validated questionnaires. RESULTS: Median PSA prior to HIFU was 6 ng/ml, the median follow-up was 61 months. 38% of the patients had low, 60% intermediate and 2% high risk disease. Median PSA level 2 years post HIFU was 1.9 ng/ml. Of the 119 control biopsies 50% had no evidence of tumor, 36% had insignificant tumor evidence and 14 % showed evidence of significant prostate cancer according to the above defined criteria. Significant infield recurrence occurred in 6 patients (4%) and significant outfield recurrence was seen in 10 patients (6%). 5 patients received a repeat HIFU, 4 patients a RT and 7 had a RP. There were no cases of distant metastasis, no need for palliative antiandrogen therapy (ADT) and no major complications. Urinary continence and erectile function were preserved in 99.5% and 85% respectively. CONCLUSIONS: At 7 years, HIFU therapy showed efficient oncological control rates with a radical treatment free survival rate of 93%. Significant infield recurrence was seen in 4% and significant outfield recurrence in 6% of patients. There was no distant metastasis and no need for palliative ADT. HIFU is associated with excellent preservation of continence and erectile function with very low morbidity. Source of Funding: Non funded © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1034 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yamini Nagaraj More articles by this author Fabian Falkenbach More articles by this author Valia Veleva More articles by this author Randi Marisa Pose More articles by this author Jonas Ekrutt More articles by this author Raisa Abrams-Pompe More articles by this author Jaideep Ratkal More articles by this author Pierre Tennstedt More articles by this author Derya Tilki More articles by this author Hans Heinzer More articles by this author Markus Graefen More articles by this author Georg Salomon More articles by this author Expand All Advertisement PDF downloadLoading ...

Proton Radiotherapy for Vestibular Schwannomas in Patients with NF2-Related Schwannomatosis: A Case Series.

(1) Background: This study aimed to evaluate the efficacy and treatment-related toxicity of proton radiotherapy (PRT) for vestibular schwannoma (VS) in patients with neurofibromatosis type 2-related schwannomatosis (NF2). (2) Methods: Consecutive NF2 patients treated with PRT for VS between 2004 and 2016 were retrospectively evaluated, focusing on tumor volume, facial and trigeminal nerve function, hearing, tinnitus, vestibular symptoms, and the need for salvage therapy after PRT. (3) Results: Eight patients were included (median age 36 years, 50% female). Median follow-up was 71 months. Five (63%) patients received fractionated PRT and three (38%) received PRT radiosurgery for VS. Six patients (75%) received prior VS surgery; three also received bevacizumab. Six patients (75%) did not require salvage therapy after PRT. Two patients (25%) with residual hearing lost it after PRT, and six had already lost ipsilateral hearing prior to PRT. Tumor and treatment-related morbidity could be evaluated in six patients. Following PRT, conditions that occurred or worsened were: facial paresis in five (83%), trigeminal hypoesthesia in two (33%), tinnitus in two (33%), and vestibular symptoms in four patients (67%). (4) Conclusion: After PRT for VS, the majority of the NF2 patients in the cohort did not require additional therapy. Tumor and/or treatment-related cranial nerve deficits were common. This is at least partly explained by the use of PRT as a salvage treatment after surgery or bevacizumab, in the majority of cases. There remains the further opportunity to elucidate the efficacy and toxicity of proton radiotherapy as a primary treatment.

Treatment strategy after the discontinuation of immunotherapy for head and neck cancer: a review

First-line systemic therapy with immune checkpoint inhibitors (ICIs) is currently the mainstream treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) that is not amenable to local therapy. However, the optimal treatment after discontinuation of ICIs is still unknown, and no large-scale analysis has been conducted in R/M SCCHN. In this narrative review, we summarize the treatment strategies available to continue ICI therapy using the currently available treatment modalities. After the administration of ICIs, unlike cytotoxic agents, the following responses are observed: durable response, pseudo-progressive disease, hyper-progressive disease, mixed response, immune-related adverse events (irAEs), and improved sensitivity to subsequent chemotherapy. Some patients show a durable response to ICIs and a good prognosis; however, many patients will require salvage therapy. We need to select the subsequent treatment according to the various responses unique to ICIs to obtain a durable response. For instance, there are reports on the effectiveness of reapplication of local therapy for a mixed response, retreatment with ICIs, and off-treatment in responsive cases complicated by irAEs. If a durable response can be maintained with ICI therapy, a long-term prognosis that cannot be obtained with conventional chemotherapy can be achieved.

High Grade B Cell NHL Outcomes: Real World Experience from the UK

Incidence of non-Hodgkin lymphoma (NHL) is increasing; it is already the sixth most common malignancy in UK (Cancer Research UK NHL incidence statistics 2022). It can present in aggressive or indolent form. Whilst for those with chemo-sensitive disease prognosis is good, with 5 year overall survival (OS) >50%, those with relapsing/refractory (R/R) forms have consistently poor outlook. Historically only 30-40% of these tolerate/respond to salvage therapy with <30% of those who respond able to proceed to consolidation with autologous stem cell transplant (ASCT). Despite this ~50% will relapse (Crump et al, Blood 2017 doi: 10.1182/blood-2017-03-769620). Recent treatment advances seek to address this area of unmet need. CAR-T cell therapy is presented as a highly effective solution for this cohort of patients. The pivotal studies leading to licensing and widespread adoption of these therapies drew comparison from SCHOLAR-1 which pooled data from 2 phase 3 clinical trials and 2 observational cohorts enabling data on 636 patients with refractory NHL to be analysed. There are challenges with this dataset and notably it does not include UK patients. We analysed patient level data for a UK NHL cohort and compare these to other, more historical data sets. 165 patients were identified. Diagnoses included primary DLBCL, DLBCL-transformed follicular lymphoma and PMBCL. Demographics: 92 male, 73 female; median age 64 (24-86yrs). Stage at diagnosis: I 10.3%, II 13.3%, III 21.2%, IV 54.5%, unknown <1%. IPI: 0- 2.4%, 1 - 13.3%, 2 - 27.3%, 3 - 26.7%, 4 - 18.8%, 5 - 3.6%, unknown 7.8%. C-MYC present in 20.7% of those where evaluated (24/116); of those 41.7% (10) double hit, 12.5% (3) triple hit. Cell of origin available for 54.5% (ACB 36.7%, GCB 63.3%). >90% considered suitable for intensive therapy; PS: 0 - 43%, 1 - 33.9%, 2 - 12.7%, 3 - 9.1%, 4 - <1%, unknown 4.2%. Nearly 2 thirds required >1 line treatment: 1 - 37%, 2 - 33.3%, 3 - 20.6%, 4 - 6.1%, 5 or greater - 3%. First line: 57.6% (95/165) 6-8 cycles R-CHOP (22% also received CNS prophylaxis - HD or intrathecal methotrexate, 16.8% additional radiotherapy (IFRT)); 10.3% abbreviated R-CHOP +/- IFRT; 9.7% dose attenuated R-CHOP, 16.4% R-CODOX-M/R-IVAC, 4.8% R-mini-CHOP, 1.8% non-intensive regimes and <1% IFRT alone. Best response was CR 52.7%, PR 11.5%, SD 13.3%, PD 11.5%, not available 10.9%. 63% (104/165) required second line treatment; time to treatment ranged from <6 months (27.9%), 6-12 months (32.7%), >12 months (37.5%), unknown in 2 cases. PS at first relapse: PS 0 - 36.6%, 1 - 45.5%, 2 - 7.1%, 3 - 7.1%, 4 - <1%. 35.6% with refractory disease had improvement in PS with treatment despite suboptimal response. 7.1% were considered too frail for further treatment. Second line therapy was primarily platinum based +/- IFRT +/- HD Mtx 71.2%; other intensive regimes included R-IVE, R-DHAP, R-ESHAP, R-CHOP and MATRIX (11.5%), less intensive regimes included R-lenalidomide, R-BP, R-miniCHOP, R-CVP, IFRT and R-CEPP (17.3%). Best response was CR 24.0%, PR 18.3%, SD 7.7%, PD 44.2%, not evaluated 5.8%. 31.7% proceeded to ASCT, 6 required >1 line of salvage therapy prior to ASCT. Exclusion basis: refractory disease 26.3%, declining PS and suboptimal response 7.5%, age only (>72years) 8.75%, frailty (PS > 2 - treatment induced/ comorbidities) 16.25%, age and frailty 13.75%, failed harvest 6.25%, patient choice 6.3%. 22 (66.6%) achieved CR after ASCT. 45 had suboptimal response to ≥2 lines intensive therapy but maintained fitness and would have been eligible for CAR-T. 47% (49/104) of those requiring salvage therapy proceeded to third line, 38.8% had refractory disease requiring treatment within 12months of first salvage treatment. 14.3% (7/49) had received ASCT. 57.1% (28/49) received intensive therapy, 18.4% (9/49) proceeded to ASCT. 42.9% were treated non-intensively. This UK dataset, analysing real world experience, highlights the challenge of high grade NHL. Whilst OS is: 2 year 63%, 5 year 29.1% with an additional 4.2% and 27.9% alive but <2 and <5 years from diagnosis respectively, for those with R/R disease OS is significantly reduced: 2 year 35.8%, 5 year 21.8%. CR rate after first line is 53.9%. However, 63% of patients required second line treatment; 4.8% relapsed >12months, 33.3% refractory; objective response rate (ORR) 42.3% (CR 24.0%), 35.8% alive at 2 years, 21.8% at 5 years. This is comparable to results from the referenced SCHOLAR-1 study supporting it as a reference point for new therapies.

Oncologic outcomes with and without amniotic membranes in robotic-assisted radical prostatectomy: A propensity score matched analysis

ObjectivePlacement of human placenta derived grafts during robotic-assisted radical prostatectomy (RARP) hastens the return of continence and potency. The long-term impact on the oncologic outcomes remains to be investigated. Our objective was to determine the oncologic outcomes of patients with dehydrated human amnion chorion membrane (dHACM) at RARP compared to a matched cohort. MethodsIn a referral centre, from August 2013 to October 2019, 599 patients used dHACM in bilateral nerve-sparing RARP. We excluded patients with less than 12 months follow-up, simple prostatectomy, and unilateral nerve-sparing. Patients with dHACM (amnio group) were 529, and were propensity score matched 1:1 to 2465 patients without dHACM (non-amnio group) and a minimum follow-up of 36 months. At the time of RARP, dHACM was placed around the neurovascular bundle in the amnio group. Continuous and categorical variables in matched groups was tested by two-sample Kolmogorov-Smirnov test and Fisher's exact test respectively. Outcomes measured were biochemical recurrence (BCR), adjuvant and salvage therapy rates. ResultsPropensity score matching resulted in two groups of 444 patients. Cumulative incidence functions for BCR did not show a difference between the groups (p=0.3). Patients in the non-amnio group required salvage therapy more frequently than the amnio group, particularly after partial nerve-sparing RARP (6.3% vs. 2.3%, p=0.001). Limitations are the absence of prospective randomization. ConclusionThe data suggest that using dHACM does not have a negative impact on BCR in patients. Outcomes of cancer specific and overall survival will require follow-up study to increase our understanding of these grafts’ impact on prostate cancer biology.

Long-Term Quality of Life of Vestibular Schwannoma Patients: A Longitudinal Analysis.

Vestibular schwannoma management aims to maintain optimal quality of life (QoL) while preventing severe sequelae of the tumor or its treatment. This study assessed long-term QoL of patients with vestibular schwannoma in relation to treatment modality and decisional regret. A longitudinal study, in which clinical and QoL data were used that were cross-sectionally acquired in 2014 and again in 2020 from the same patient group. A tertiary expert center for vestibular schwannoma care in the Netherlands. QoL was measured by the Penn Acoustic Quality of Life (PANQOL) scale. Changes in time were assed using a linear mixed model. In addition, the Decision Regret Scale was analyzed. Of 867 patients, 536 responded (62%), with a median follow-up of 11 years. All PANQOL subdomain scores remained stable over time and did not exceed minimal clinically important difference (MCID) levels. Time since treatment did not affect QoL. Patients had comparable average QoL scores and proportions of patients with changing QoL scores (ie, exceeding the MCID) over time, irrespective of the received initial treatment. Female patients and those who required salvage therapy (either by radiotherapy or surgery) reported a lower QoL. The latter patient group reported the highest decisional regret. On average, the long-term QoL of patients with vestibular schwannoma is comparable for patients under active surveillance and those who have received active treatment, and it remains stable over time. This suggests that, on average, preservation of QoL of patients with vestibular schwannoma is feasible when adequately managed.

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With or Without Radiation Therapy: A 25-Year Retrospective Analysis of a Single-Institution Experience

PurposeAtypical (World Health Organization [WHO] grade 2) and malignant (WHO grade 3) meningiomas have high rates of local recurrence, and questions remain about the role of adjuvant radiation therapy (RT) for patients with WHO grade 2 disease. These patients frequently require salvage therapy, and optimal management is uncertain given limited prospective data. We report on the long-term outcomes for patients with atypical and malignant meningiomas treated with surgery and/or RT at our institution. Methods and MaterialsData were collected through a retrospective chart review for all patients with WHO grade 2 or 3 meningiomas treated with surgery and/or RT at our institution between January 1992 and March 2017. Progression-free survival (PFS) and overall survival (OS) were described using the KaplanMeier estimator. The outcomes in the subgroups were compared with a log-rank test. A Cox proportional hazards model was used for the univariable and multivariable analyses of predictors of PFS. ResultsA total of 66 patients were included in this analysis. The median follow-up was 12.4 years overall and 8.6 years among surviving patients. Fifty-two patients (78.8%) had WHO grade 2 meningiomas, and 14 patients (21.2%) had WHO grade 3 disease. Thirty-six patients (54.5%) were treated with surgery alone, 28 patients (42.4%) with surgery and adjuvant RT, and 2 patients (3%) with RT alone. Median PFS and OS were 3.2 years and 8.8 years, respectively. PFS was significantly improved with adjuvant RT compared with surgery alone (hazard ratio, 0.36; 95% confidence interval, 0.18-0.70). Patients with Ki-67 index >10% showed a trend toward worse PFS compared with patients with Ki-67 ≤10% (hazard ratio, 0.51; 95% confidence interval, 0.25-1.04). No significant differences in PFS or OS were observed with respect to Simpson or WHO grade. ConclusionsFor patients with atypical or malignant meningiomas, adjuvant RT was associated with significantly improved PFS, and Ki-67 index >10% was associated with a trend toward worse PFS. Given the long-term survival, high recurrence rates, and efficacy of salvage therapy, patients with atypical and malignant meningiomas should be monitored systematically long after initial treatment.

Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis

Background:Although the prognosis for children with Hodgkin lymphoma (HL) is excellent, up to 25% of patients experience relapse and require salvage therapy. Event-free survival (EFS) for patients with relapsed or refractory disease (R/R) who require high-dose therapy with autologous stem cell transplantation (ASCT) is between 31-67% (Daw, 2011), and efforts to improve these outcomes are an area of urgent clinical need. Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate combined with monomethyl auristatin E. The phase III AETHERA study (NCT01100502) was a randomized, placebo-controlled trial that demonstrated consolidation with BV following ASCT for adults with R/R HL improved progression-free survival (PFS) in comparison to placebo (5-year PFS 59% vs. 41%) in patients identified as having a high-risk of post-ASCT progression (Moskowitz, 2015, 2018). However, there is limited data on post-ASCT BV consolidation in pediatric patients. Here, we report a retrospective multi-center study of BV as consolidation post-ASCT in pediatric patients with R/R HL.Patients and Methods:We performed a retrospective analysis of pediatric patients aged ≤ 21 years who received BV as consolidative therapy following ASCT for the treatment of relapsed/refractory HL. Data was collected on disease risk factors (refractory disease or relapse ≤ 12 months after frontline therapy, best response of partial remission or stable disease to salvage therapy, presence of extranodal involvement, presence of B symptoms, and number of systemic treatments pre-ASCT ≥ 2), treatment history, BV-related toxicity, and response to therapy. The primary endpoint was 3-year EFS. Events were defined as relapse, progression of disease, or death from any cause.Results:Seventy patients were identified from 14 academic centers. Eighteen received BV >90 days after ASCT and were excluded due to significant delay in initiation of BV. Of the remaining 52 patients, the median age at diagnosis was 15 years (range 4-21), and the median age at diagnosis of R/R disease was 16 years (range 8-22). Twenty-eight patients (54%) were male, 13 (25%) had B symptoms, 19 (37%) had extranodal disease. Six patients (12%) had primary refractory disease and 24 patients (47%) relapsed <12 months after frontline therapy. The median number of salvage regimens received pre-ASCT was 2 (range 1-7). Forty-two patients (81%) received BV as part of a pre-ASCT salvage regimen, 4 (8%) of whom did not receive BV in the regimen immediately prior to ASCT. Radiation therapy was used pre or post-ASCT in 16 patients (31%). Prior to ASCT, 40 patients (77%) were PET-negative (Deauville 1-3), 11 (21%) were PET-positive (Deauville 4-5), and response in 1 (2%) was unknown.The median time from ASCT to the start of BV consolidation was 52 days (range 30-90 days). The most frequent adverse events were peripheral neuropathy of any grade (sensory 19/52 [37%]; motor (14/52 [27%]), and cytopenias (grade 3 or 4: (25/52 [48%]), including neutropenia (13/52 [25%]), thrombocytopenia (7/52 [14%]), and anemia (5/52 [10%]). Three patients (6%) experienced infusion-related reactions. The median number of BV cycles completed post-ASCT was 12 (range 1-17), and 16 patients (31%) completed the full 16 cycles of BV. The most common reason for premature termination was adverse effects (22/36 [61%]). Additional reasons included: physician plan for shorter duration (4/36 [11%]), patient/family decision (3/36 [8%]), and progression (1/36 [3%]). Treatment was still ongoing in 3 patients and reason for premature termination was not reported for 17/36 patients (47%).With a median follow of 2.8 years (range 0.1 to 6.25 years) the three-year EFS was 92% [95%CI: 83-100]. Patients with 0-1 risk factors (15/52 [29%]) and ≥ 2 risk factors (37/52 [71%]), had a 3-year EFS of 100% and 90% [95%CI: 79-100], respectively. Fifty patients (96%) are alive with no evidence of disease, while 2 (4%) patients are alive with disease. No deaths have occurred.Conclusion:The use of post-ASCT BV consolidation for pediatric patients with R/R HL is associated with a favorable safety and tolerability profile. In this cohort, the combination of salvage therapy, HD-chemotherapy/ASCT, and BV consolidation resulted in extremely promising outcomes and warrants further investigation in a prospective pediatric trial. [Display omitted] DisclosuresLeger: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbott Diagnostics: Research Funding. Roth: Merck: Consultancy; Janssen: Consultancy.

Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Introduction:Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution.Methods:All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA).Results:114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the ‘high risk criteria’ as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease.The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%).After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma).Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of ‘low risk’ patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2).Conclusion:After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. [Display omitted] DisclosuresWhite: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

ADAPT First-Line Strategy for MCA Mainstem Occlusion; Analysis for Optimal Salvage Therapy and its Related Factor

ObjectivesA direct first-pass aspiration technique (ADAPT) is an attractive interventional technique for mechanical thrombectomy (MT), which could achieve recanalization quickly and safely at a small amount of material resources. To clarify its usefulness, our ADAPT first-line strategy for middle cerebral artery (MCA)-mainstem occlusion was retrospectively analyzed. Materials and MethodsWe reviewed 54 consecutive patients who underwent MT for MCA-mainstem occlusion using ADAPT first-line strategy. A salvage procedure was concurrently conducted in cases that failed to achieve successful recanalization by ADAPT attempt alone. Procedural and clinical outcome were assessed in both ADAPT alone and Salvage groups. Further investigation was performed in cases that required salvage procedure to determine the reason, risk factors, and optimal procedure. ResultsForty-one patients (75.9%) were able to achieve successful recanalization with ADAPT technique alone. In salvage group, the procedural time was longer, and rates of successful recanalization were lower than in ADAPT-alone group. No significant difference in the rates of favorable outcomes was observed. Among 13 patients who required salvage therapy, the major reason (eight cases) was intra-procedural “thrombus distal migration”. Failure of recanalization was seen in two cases due to “inaccessibility”. In patients who had “thrombus distal migration”, occlusion in the proximal portion was more frequently observed than in patients who did not (p = 0.032, 63.6% vs. 23.3%). ConclusionsOur ADAPT first-line strategy for MCA-mainstem occlusion demonstrated favorable procedural and clinical outcomes, even in cases that required additional procedures. Further investigation and better understanding are required to refine this promising procedure.