One-year One-year Overall Survival Research Articles

Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

Evaluation of the Local Control Rate and Late Toxicity of High-Dose-Rate Interstitial Brachytherapy in Tongue Squamous Cell Carcinoma

Background: Tongue Squamous Cell Carcinoma (TSCC) is one of the most consequential oral Squamous Cell Carcinomas (SCC) worldwide.
 Methods: This retrospective cross-sectional study was conducted on 29 TSCC patients treated with High Dose Rate Brachytherapy (HDR-BT) with or without External Beam Radiotherapy (EBRT) between 2017-2020. Patients without distant metastasis at the time of treatment and at least one year after completion of brachytherapy were included.
 Results: One-year Overall Survival (OS), Disease-Free Survival (DFS), and Local Control Rate (LCR) were 82.8, 79.3, and 100%, respectively. 6 patients (20.7%) had distant metastasis, of which 5 (17.2%) died. Local recurrence was not observed in any patients, and only one (3.4%) regional recurrence occurred. The most common late toxicity of HDR-BT was dry mouth (79.2%) and dysarthria (66.7%). There were no severe and life-threatening complications (grades 3 and 4) during one year. Also, 79.2% of the patients had good functional performance. One-year OS, the significant difference between the two groups of HDR-BT with and without EBRT (p=0.055).
 Conclusion: Our findings indicated that the HDR-BT increases the OS of TSCC patients more than EBRT without developing grade 3-4 AEs and metastasis. We showed that the mean 3.2 ±0.7 Gy of HDR-BT has more OS compared to EBRT.

Comparison of Safety and Efficacy between Venetoclax Combined with CAG (cytarabine, aclarubicin, G-CSF) Regimen and CAG Regimen Alone in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Background: Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) have dismal outcomes, representing an urgent unmet need. The BCL2 inhibitor venetoclax has exhibit encouraging anti-tumor activity in AML. The clinical efficacy of the CAG regimen in patients with R/R AML has been confirmed in previous studies. The aim of this study was to retrospectively compare the safety and efficacy of the combination of venetoclax with CAG regimen and CAG alone in patients with R/R AML. Patients and methods: We retrospectively reviewed and compared the efficacy and safety of venetoclax combined with the CAG regimen (Ven-CAG group, n=37) and CAG regimen alone (CAG group, n=37) for 74 patients with R/R AML treated at our institution between August, 2016 and March 2023. The patients included those who were refractory to at least one cycle of induction chemotherapy, and patients with relapsed leukemia. According to the duration from complete remission (CR) to relapse, the relapsed patients were further divided into two subgroups, the favorable-risk relapsed group (the duration≥12 months) and the poor-risk relapsed group (the duration<12 months). The incidence of composite complete remission (CCR), minimal residual disease (MRD) status, one-year overall survival (OS), and adverse events (AEs) were analyzed and compared in two groups. Results: Patient age, sex, ELN risk stratification, disease status, risk stratification according to the duration from CR to relapse were comparable between two groups (Table 1). The CCR of Ven-CAG group was 78.4% (29/37)，which was superior to 56.8% (21/37) of CAG group (P=0.047) . Furthermore, the rate of MRD elimination in patients who achieved CCR in Ven-CAG group was significantly higher than that in CAG group [44.8% (13/29) vs. 9.5% (2/21), P= 0.007] (Table 2). The rate of MRD elimination in favorable-risk relapsed group (CR to hematological relapse ≥12 months) was higher in Ven-CAG group [100% (5/5) vs. 25% (1/4), P= 0.048]. The one-year OS were 78.4% (95% CI, 62.3%-94.5%) and 66.7% (95% CI, 51.2%-82.2%) in Ven-CAG and CAG group (P=0.225), respectively. The incidences of grade 3-4 hematologic AEs in Ven-CAG group and CAG group were 100% (37/37) and 97.3% (36/37), respectively (P=1.000). The incidences of febrile neutropenia were 67.6% (25/37) and 62.2% (23/37), respectively (P=0.626). Among patients who achieved CCR, the median time for neutrophil recovery in the Ven-CAG group and CAG group were 8 (3-30) days and 9.5 (3-31) days (P=0.781), while the median time for platelet recovery was 9 (3-28) days and 8 (3-19) days (P=0.708). The incidences of grade 3-4 non-hematologic AEs were comparable in Ven-CAG and CAG group (32.4% vs. 35.1%, P=0.806). The most common nonhematologic AEs were infections, with the incidences of 18.9% and 27%, respectively (P=0.407). No patients died within 4 weeks after initiating the induction course in Ven-CAG group. There was one case of early death during induction in CAG group due to cerebral hemorrhage. Conclusions: Venetoclax added to CAG regimen was safe and active in patients with R/R AML, producing higher CCR and MRD-negative remissions than CAG regimen alone. These results highlight the incremental benefit of venetoclax added to CAG regimen. This requires further verification through prospective, larger size clinical trials.

Efficacy and safety of osimertinib for leptomeningeal metastases from EGFR-mutant non-small cell lung cancer: a pooled analysis

BackgroundThe aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).MethodsWe conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs).ResultsA total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies.ConclusionsOur study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.

Prevalence of Poverty and Hunger at Cancer Diagnosis and Its Association with Malnutrition and Overall Survival in South Africa

Many South African children live in poverty and food insecurity; therefore, malnutrition within the context of childhood cancer should be examined. Parents/caregivers completed the Poverty-Assessment Tool (divided into poverty risk groups) and the Household Hunger Scale questionnaire in five pediatric oncology units. Height, weight, and mid-upper arm circumference assessments classified malnutrition. Regression analysis evaluated the association of poverty and food insecurity with nutritional status, abandonment of treatment, and one-year overall survival (OS). Nearly a third (27.8%) of 320 patients had a high poverty risk, associated significantly with stunting (p = 0.009), food insecurity (p < 0.001) and residential province (p < 0.001) (multinomial regression). Stunting was independently and significantly associated with one-year OS on univariate analysis. The hunger scale was significant predictor of OS, as patients living with hunger at home had an increased odds ratio for treatment abandonment (OR 4.5; 95% CI 1.0; 19.4; p = 0.045) and hazard for death (HR 3.2; 95% CI 1.02, 9.9; p = 0.046) compared to those with food security. Evaluating sociodemographic factors such as poverty and food insecurity at diagnosis is essential among South African children to identify at-risk children and implement adequate nutritional support during cancer treatment.

Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.

Abstract B121: HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplant cyclophosphamide improves clinical outcomes for racial and ethnic minority patients with hematologic malignancies

Abstract Introduction: Racial and ethnic disparities exist in three areas related to hematopoietic cell transplantation (HCT): donor availability, access, and post-HCT outcomes. A significant barrier to access to HCT for patients (pts) of racial or ethnic minorities (REM) is the limited availability of fully matched donors (i.e., grafts matched at HLA-A, -B, -C, and -DRB1 loci) in volunteer registries. While mismatched unrelated donor (MMUD) grafts (i.e., &amp;lt;7/8 match) can be offered to pts without matched donors, MMUD HCT results in poor survival when traditional graft-versus-host disease (GVHD) prophylaxis (PPx) is used. GVHD PPx with post-transplantation cyclophosphamide (PTCy) is associated with favorable survival after haploidentical HCT, and promising outcomes have been reported in a prospective multicenter study utilizing PTCy in MMUD HCT. Herein, we analyzed the outcomes of an ethnically diverse cohort of pts who underwent MMUD HCT with PTCy at two large urban transplant centers. Objectives and Methods: Subjects receiving HCT from an MMUD from 2010-to 2020 at the University of Miami and Memorial Sloan-KetteringCancer Center were included. Pts were stratified by age, HCT indication, race/ethnicity, graft type, conditioning intensity, disease status, and degree of HLA mismatch. The primary study endpoint was one-year overall survival (OS). Secondary endpoints were event-free survival (EFS), non-relapse mortality (NRM), and cumulative incidence of acute and chronic GVHD. Results: A total of 82 pts were evaluated. The median age at HCT was 60 years (21-75), the most common indication for HCT was acute leukemia (51%), 41% of pts received an ablative conditioning regimen, and 50% received peripheral blood (PB) grafts. Forty-four percent identified as non-Hispanic white (NHW), and 56% identified as REM (Non-Hispanic Black: 30%; Hispanic: 64%; Asian/Pacific: 4.3%). The two groups (NHW vs. REM) were well-matched for leading HCT indication, disease-risk index, degree of mismatch, and disease status at HCT. REM pts were younger (median age at HCT 65 vs 56 years for NHW, p=0.001) and more likely to receive a PB graft (63% vs 40%, P = 0.04). One-year OS was 75%, EFS was 69%, and NRM was 16% for the entire cohort. Grade 3-4 acute GVHD at day 180 post-HCT was 15%, and one-year severe chronic GVHD was 9%. OS was comparable between 7/8-matched and highly-mismatched (&amp;lt;6/8) HCT recipients (75% vs. 76%, respectively; P &amp;gt;0.9). There were no differences in one-year OS (77% vs 74%, p = 0.9) and EFS (63% vs 72%, p = &amp;gt;0.9) between NHW and REM pts. Similarly, rates of acute (17% vs 13%, p = 0.5) and chronic GVHD (5.7% vs 11%, p = 0.5) were comparable between NHW and REM pts. Conclusion: PTCy resulted in encouraging clinical outcomes following MMUD HCT. Post-HCT OS, RFS, and GVHD rates were comparable between NHW and REM pts and those receiving 7/8 or highly mismatched grafts. Favorable post-HCT outcomes following MMUD with PTCy may increase HCT utilization and access for REM pts. Citation Format: Antonio M. Jimenez Jimenez, Sunil Iyer, Krishna Komanduri, Samantha Brown, Trent Wang, Stephanie Chinapen, Denise Pereira, Sean Devlin, Mark Goodman, Amer Beitinjaneh, Craig Sauter, Lazaros Lekakis, Miguel Angel Perales, Doris Ponce, Brian Shaffer. HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplant cyclophosphamide improves clinical outcomes for racial and ethnic minority patients with hematologic malignancies [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B121.

A retrospective evaluation of the presentation, prognostic factors and outcomes of neuroblastoma in Ugandan children

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The complete burden and outcomes in Uganda are unknown. The study was a multicenter retrospective chart review of children aged between 0 to 15 years diagnosed with NB from 2010 to 2020. Demographic, clinical and tumor-related characteristics were extracted for analysis. Kaplan-Meier survival curves and Cox regression models were used to determine the one-year overall survival (OS) and identify prognostic factors. Seventy-five patients were evaluated, with a median age at diagnosis of 48 months (IQR 26-108 months). Fever (74.7%), weight loss (74.7%), high blood pressure (70.3%) and abdominal swelling/mass (65.3%) were the most common features at diagnosis. Suprarenal tumors (52%) and stage 4 disease (70.7%) were also common. The one-year OS was 60.0% (95%CI 56.8%; 64.3%) with a median survival time of 12.6 months (95% CI: 8.1; 20.8). The one-year OS for non-metastatic and metastatic disease was 67.3% and 42.6% (p = 0.11) respectively. Leukocytosis (p < 0.001) at diagnosis was of prognostic significance while clinical remission after induction chemotherapy (p < 0.001) provided survival advantages. Children who received maintenance chemotherapy had a longer median survival time of 38.5 months (range 10.8–69.5). Age (p = 0.001), lung metastasis (p < 0.001), and leukocytosis (p < 0.001) remained significant on multivariate analysis. In this Ugandan study, leukocytosis was a clinical predictor of prognosis, metastatic disease had management challenges and maintenance chemotherapy prolonged the survival time but not OS.

Chidamide Plus Prednisone, Cyclophosphamide, and Thalidomide (CPCT) for Relapsed or Refractory Peripheral T-Cell Lymphoma: A Multicenter Phase II Trial

Purpose: Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of aggressive lymphomas that portends an unfavorable outcome. Although the treatment of PTCL has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory-particularly for relapsed or refractory (R/R) patients. We herein conducted a prospective, single-arm phase II clinical trial to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate standard chemotherapy for a variety of reasons. Methods: This was an open-label, single-arm, multicenter pivotal phase II study in which patients were enrolled at 9 centers. The flow chart of the CPCT regimen: a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. The CPCT regimen was administered orally until disease progression or unacceptable toxicity as follows: chidamide at 30 mg twice weekly, prednisone at 20 mg daily after breakfast, cyclophosphamide at 50 mg daily after lunch, and thalidomide at 100 mg daily at bedtime. Our primary objective was to assess overall response rate (ORR) after treatment with CPCT, with secondary objectives to evaluate the duration of response, one-year overall survival (OS), and one-year progression-free survival (PFS). Results: Forty-five patients were ultimately enrolled in the present study for response and safety assessments from August 2016 to April 2021 with respect to Chinese patients (the characteristics of the 45 patients with at least one treatment response assessment are listed in Figure 1A). Twenty-three patients (51.1%) were heavily pretreated before enrollment. Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% and 28.9%, respectively, and after a median follow-up period of 56 months, the median PFS and OS were 8.5 and 17.2 months, respectively (Figure 1B). The median median duration of response (DOR) was six months with a range of 0.7-71.5 months, and most responders (41 patients, 91.1%) had a DOR more than three months. Twenty-eight patients (62.2%) exhibited a DOR over six months and 17 patients (37.8%) had a DOR over 12 months. The one-year PFS and OS rates were 42.2% (95% CI, 27.7%‒56.7%) and 57.8% (95% CI, 43.3%‒72.3%), respectively, and the five-year PFS and OS rates were 21.2% (95% CI, 7.9%‒34.5%) and 43.8% (95% CI, 28.3%‒59.3%), respectively. Although subgroup survival analysis indicated no significant differences among different histopathologies (Figure 1C and D), the median PFS (p<0.001) and OS (p<0.001) were not attained for patients who achieved CR/CRu (N=13) (Figure 1E and F). The most common grade 3/4 adverse event was neutropenia (24.5%), but we observed no treatment-related mortality. Conclusions: In conclusion, the all-oral CPCT regimen was a well-tolerated and effective treatment for R/R PTCL patients who could not tolerate standard chemotherapy for a variety of reasons. However, further studies that entail a larger sample size in different subtypes of PTCL are still required. This trial was registered in ClinicalTrials.gov (NCT02879526). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S240: CD7 CHIMERIC ANTIGEN RECEPTOR T CELLS BRIDGING TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IMPROVED DISEASE-FREE SURVIVAL IN REFRACTORY/RELAPSED T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

Background: Our previous clinical study has shown that the patients with refractory/relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL) have achieved 90% complete remission (CR) with donor-derived CD7 chimeric antigen receptor T cells (CART), but some cases have developed donor-recipient mixed chimerism and remarkable pancytopenia (Pan J. et al. JCO 2021). It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Aims: In current study, the safety and efficacy of allo-HSCT in r/r T-ALL after CD7-CART are investigated. Methods: From February 2018 to December 2021, total 57 patients with r/r T-ALL who underwent allo-HSCT in our hospital were included. The median age was 13(4-69) years old. Extramedullary disease (EMD) was found in 32 patients (56.1%). Somatic gene mutations (NOTCH 18, IL7R 3, JAK 2, FBXW7 2, WT1 2, NRAS 2) were detected in 17 patients. Eighteen patients who were resistant to chemotherapy received CD7-CART (CART group) before transplant, and all patients except one achieved CR. Thirty-nine r/r T-ALL patients were managed with chemotherapy before transplant (non-CART group), and 25 patients achieved CR (CR arm), 14 patients were in non-remission (NR) (NR arm) before transplantation. Conditioning regimens in CART group were either busulfan/fludarabine (n=12) or TBI/fludarabine (n=6). Conditioning regimens in non-CART group were either busulfan/fludarabine (n=11) or TBI/ fludarabine (n=28). ATG was used for haploidentical or unrelated transplants. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for GVHD prophylaxis. Results: In CART group, the median time of neutrophils and platelets engraftment were 15 (10-22) and 18 (8-50) days. With the median follow-up 283 (14-496) days, 13 patients survived and 5 patients died (infection 4, cerebral hemorrhage 1). Three of 18 (16.7%) patients relapsed (CD7- 1, CD7 + 2) after transplantation and have been receiving treatment so far. One-year overall survival (OS) and disease-free survival (DFS) were 77.8% and 61.2%. Transplantation-related mortality (TRM) was 16.6%. In non-CART group, the median time of neutrophils and platelets engraftment were 15 (10-22) and 15 (8-28) days. Total 25 patients survived and 14 cases died (relapse 3, infection 4, GVHD 1, multiple organ failure 6). Fifteen of 39 (38.5%) patients relapsed. In CR arm, with the median follow-up 637(9-1357) days, one-year OS and DFS were 71.0% and 59.2%. In NR arm, with the median follow-up 517 (7-513) days, one-year OS and DFS were 59.2% and 40%. TRM was 28.2%. Summary/Conclusion: Donor-derived CD7-CART followed by allo-HSCT has achieved similar survival (OS, DFS) and lower relapse rate and TRM compared with chemotherapy followed by allo-HSCT in r/r T-ALL. CD7-CART may result in better disease control which will translate into less disease recurrence after transplant.

Graft Inflow Modulation in Living Donor Liver Transplantation with a Small-for-Size Graft: A Systematic Review and Meta-Analysis.

Introduction: Small-for-size graft and consequently small-for-size syndrome (SFSS) is an important issue for adult living donor liver transplantation (LDLT). The optimal intra- and postoperative prevention and management strategies for SFSS remain unclear. We aimed to analyse and compare the existing strategies of portal inflow modulation (PIM) and conduct a meta-analysis of studies comparing various PIMs. The primary outcome was the incidence SFSS. Methods: The Google Scholar, Embase, PubMed, and Cochrane Library databases were systematically searched. Both fixed-and random-effects models were used to perform the meta-analysis. Results: Twenty-five studies were selected from a pool of 830 studies, of which 13 compared available surgical techniques between cohorts with and without PIM, and 12 reported outcomes of patients who underwent LDLT and developed SFSS. The incidence rate of SFSS was significantly lower in the PIM cohort than in the non-portal inflow modulation (NPIM) cohort. One-year overall survival (OS) and the re-transplantation rate were significantly better in the PIM cohort than in the NPIM cohort. Conclusion: In LDLT patients diagnosed during the reperfusion period with increased portal venous pressure and/or flow, application of PIM significantly decreased the incidence rate of SFSS and demonstrated significantly better one-year OS.

High-dose Chemotherapy Response in Adults with Relapsed/Refractory Small Round Cell Tumours.

To demonstrate the treatment responses, survival analysis, and treatment-related mortality characteristics of high-dose chemotherapy (HDC) in patients with relapsed/refractory Ewing sarcoma (ES), osteosarcoma, rhabdomyosarcoma (RMS) and medulloblastoma (MB). Observational study. Department of Medical Oncology, University of Health Sciences, Gulhane School of Medicine, from January 2016 and April 2020. Clinical features and follow-up data of relapsed/refractory ES, osteosarcoma, RMS and MB patients treated with HDC were recorded from the patients' registration database of the hospital. Patients <16 years and those whose medical records were not available were excluded. Progression-free survival (PFS), one-year overall survival (OS) rates and treatment-related mortality (TRM) after the HDC were determined. Ifosfamide, carboplatin and etoposide (HD-ICE) were used as the HDC protocol in all patients. Thirty-seven adult patients were included. PFS was determined as 2.70 ± 0.97 months, 11.57 ± 3.63 months, 3.47 ± 0.44 months and 2.96 ± 0.91 months, for ES, MB, RMS and osteosarcoma, respectively. One-year OS rate was 44.8 ± 14.8% for ES; 75 ± 15.8% for MB. In ES, PFS was found to be better in males than females (p = 0.025). No patient died during HD-ICE. Mortality was observed most frequently in the RMS in the first 100 days (25%). HD-ICE treatment may be an option in relapsed/refractory small round cell tumours (SRCT). Significant progression-free survival can be achieved in patients who received at least two lines of treatment, with acceptable treatment-related mortality. Key Words: Small round cell tumours, Ewing sarcoma, Osteosarcoma, Rhabdomyosarcoma, Medulloblastoma, High-dose chemotherapy, Autologous stem cell transplantation.

PCN114 Investigating Secular Trends in the Survival of Melanoma Patients in England

Understanding survival through use of population level cancer registry data can help to describe standards of care, identify unmet need and understand changes in the therapeutic landscape. We assessed the availability of such data from Public Health England (PHE) to study malignant melanoma survival in England. De-identified cancer registry data were obtained from PHE after NHS ethics committee approval. Survival was estimated in a cohort of patients diagnosed with malignant melanoma in England from 1995 to 2016. The data included numerous clinical characteristics (e.g. tumour site, cancer morphology, behaviour, T,N,M and pathological stage) and an indicator of socioeconomic status (SES). Primary endpoints measured from time of diagnosis, were one-year overall survival (OS) and one-year relative survival (RS) relative to the total population of England (1995 to 2016). One-year OS by disease stage and SES was also investigated. Data were available for 184,864 melanoma patients. Disease stage was missing in 57% of patients (79% between 1995 and 2011, and 13% between 2012 and 2016). No information was available on relevant behaviours such as smoking. In the overall population, average one-year OS and RS were high (94% and 97% respectively). Between 1995 and 2016, one-year OS and RS increased from 92% to 95%, and from 95% to 99% respectively. The average OS for Stage I, II, III and IV melanoma was 99%, 94%, 90% and 48% respectively. Probability of survival was also higher with greater SES (95% versus 92% for the highest and lowest quintile). England’s PHE data provides a useful resource to study trends in melanoma survival over time, with rich clinical detail. While it is limited by high levels of missing data on disease stage in earlier years, it nevertheless provides a robust source of data to understand population level disease epidemiology.

#8: Survival Analysis in Childhood Acute Myeloblastic Leukemia: Do Infection and Lymphocyte-Mediated Immune Response Play a Role?

Abstract Background Acute myeloblastic leukemia (AML) is the second most prevalent cancer among Indonesian children. In contrast, to those of acute lymphoblastic leukemia (ALL), a number of studies reported unfavorable outcomes following the initiation of cytostatic protocols for childhood AML. In addition, our previous study showed that Gram-negative bacterial infection constitutes the major cause of treatment-related mortality in children with AML. These findings raised a question on the prognostic role of diagnostic lymphopenia, which represents the immunosuppressive state, as demonstrated in adult patients with solid tumors. Methods A retrospective cohort study, which involved children younger than 18 years of age with the newly diagnosed, non-M3 AML, was conducted. These children were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the period of 2011–2019 and received National Pilot Protocol (2011–2016), Pediatric AML Protocol (2016–2018), and International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) Protocol with prephase (2018–2019). One-year overall survival (OS) was analyzed, using diagnostic absolute lymphocyte counts (ALC0) of more than 4.5 × 109/L and less than 4.5 × 109/L as the determinants, in accordance with those reported in a number of studies on adult AML. Results Sixty-five children, which consisted of 41 (63%) children with ALC0 of more than 4.5 × 109/L and 24 (37%) children with ALC0 of less than 4.5 × 109/L, were eligible for this study. Of these 65 children, 56 (86%) children received Cytosine arabinoside in the first week of treatment (National Pilot Protocol and Pediatric AML Protocol), while 9 (14%) children did not (SIOP PODC Protocol with prephase). OS analysis showed that 44% and 19% of children with ALC0 of more than 4.5 × 109/L and ALC0 of less than 4.5×109/L, respectively, were alive within the first year of treatment. Cox-regression analysis, however, failed to reach statistical significance [hazard ratio (HR), 0.63; 95% confidence interval (95% CI), 0.33–1.18; P = 0.15]. Conclusion Despite lacked statistical significance, our study showed the superior one-year OS in children with ALC0 of more than 4.5 × 109/L. Our findings, therefore, might indicate the prognostic role of infection and lymphocyte-mediated immune response in childhood AML.

#23: Survival Analysis of Childhood Acute Myeloblastic Leukemia in a Limited Resource Center: Do Infection and Lymphocyte-Mediated Immune Response Play a Role?

Abstract Background Acute myeloblastic leukemia (AML) is the second most prevalent cancer among Indonesian children. In contrast to those of acute lymphoblastic leukemia (ALL), a number of studies reported unfavorable outcomes following the initiation of cytostatic protocols for childhood AML. In addition, our previous study showed that Gram-negative bacterial infection constitutes the major cause of treatment-related mortality in children with AML. These findings raised a question on the prognostic role of diagnostic lymphopenia, which represents the immunosuppressive state, as demonstrated in adult patients with solid tumors. Methods A retrospective cohort study, which involved children younger than 18 years of age with the newly diagnosed, non-M3 AML, was conducted. These children were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the period of 2011–2019 and received National Pilot Protocol (2011–2016), Pediatric AML Protocol (2016–2018), and International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) Protocol with prephase (2018–2019). One-year overall survival (OS) was analyzed, using diagnostic absolute lymphocyte counts (ALC0) of more than 4.5 × 109/L and less than 4.5 × 109/L as the determinants, in accordance with those reported in a number of studies on adult AML. Results Sixty-five children, which consisted of 41 (63%) children with ALC0 of more than 4.5 × 109/L and 24 (37%) children with ALC0 of less than 4.5 × 109/L, were eligible for this study. In a multivariate logistic regression analysis, compared with those of diagnostic white blood cell and peripheral blood myeloblast counts, treatment-related pneumonia, gastrointestinal tract infection, and sepsis were the most responsible factors for the occurrence of death within the first year of treatment [relative risk (RR), 2.82; 95% confidence interval (95% CI), 0.99–8.04; P = 0.05]. OS analysis showed that 43% and 16% of children with ALC0 of more than 4.5 × 109/L and less than 4.5 × 109/L, respectively, were alive within the first year of treatment. Cox-regression analysis, however, failed to reach statistical significance [hazard ratio (HR), 0.63; 95% CI, 0.33–1.18; P = 0.15]. Conclusion Despite lacked statistical significance, our study showed the superior one-year OS in children with ALC0 of more than 4.5 × 109/L. Our findings, therefore, might indicate the prognostic role of infection and lymphocyte-mediated immune response in childhood AML.

Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients.

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (177Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative 177Lu-DOTAGA-(I-y)fk(Sub-KuE) (177Lu-PSMA I&T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of 177Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p < 0.0001; 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: 177Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. 68Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.

Stereotactic Body Radiation Therapy (SBRT) for Liver Oligometastases: Outcomes and Safety.

The aim of this study was to investigate adverse effects, progression free survival (PFS), one-year local control (LC) and one-year overall survival (OS) of patients with liver oligometastases treated with stereotactic body radiotherapy (SBRT), and whether there was a significant difference in these parameters in patients with primary colorectal cancer compared to other tumor localizations. Patients were simulated using four-dimensional computed tomography (4DCT). Using volumetric modulated arc therapy (VMAT) technique, SBRT was performed on 16 patients with <3 liver metastases. The prescribed dose was 60 Gy in 8 fractions (BED 105 Gy). Cone beam CT (CBCT) was used for image guidance before each fraction with online correction. There were no adverse effects. Median PFS for all patients, patients with primary colorectal cancer, and patients with primary non-colorectal cancer was 11 months (SE 2.1), 16 months (SE 2.8), 6 months (SE 2.4), respectively. There was no significant difference in the PFS for these two observed groups (P=0.09). The one-year LC was 62.5%. Patients with primary colorectal cancer had one-year LC of 87.5%, while the group of patients with primary non-colorectal cancer had one-year LC of 37.5% (P=0.063). The total one-year OS was 87.5%. In the group of patients with primary colorectal cancer, the one-year OS was 100%, while in the group of patients with primary non-colorectal cancer, the one-year OS was 75% (P=0.317). SBRT with 8 × 7.5 Gy can be safely delivered and is effective method of treating liver oligometastases.

Real-world one-year overall survival among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan in the NAPOLI-1 based regimen.

392 Background: Pancreatic cancer remains one of the most lethal cancers in the United States (US) with a 5-year relative survival of 9%. Among patients who received liposomal irinotecan + 5-fluorouracil (5-FU) and leucovorin in the NAPOLI-1 study, a randomized phase 3 study in patients with mPDAC previously treated with gemcitabine-based therapy, 25% (n = 29) were alive at ≥ 1 year. This study examines the real world one-year survival of patients with mPDAC treated with liposomal irinotecan as a doublet with 5-FU in the NAPOLI-1 based regimen. Methods: This retrospective observational study utilized the Flatiron Health EHR database from over 280 cancer clinics in the US. Data were analyzed for adult patients with mPDAC treated with liposomal irinotecan-based regimens between November 2015 and July 2020. Patient characteristics and one-year overall survival (OS) based on Kaplan-Meier estimates were assessed. Cycles were defined as unique days with an administration of liposomal irinotecan. Results: There were 669 patients (median age: 69y, IQR: 62-75) included in the study. ECOG performance status (PS) of 0-1 and 2+ were reported for 78.3% (n = 396) and 21.7% (n = 110) of patients, respectively. ECOG PS was not captured for 24.4% (n = 163) of patients. 16.3% (n = 109) of patients initiated liposomal irinotecan-based in the first line (1L) metastatic setting, 47.5% (n = 318) in second line (2L), and 36.2% (n = 242) in the third line or later (3L+). The median number of cycles received was 4 (IQR: 2 – 8). Among all patients, one-year OS was 17.2% (95% CI: 14.3% - 20.7%). One-year OS was 31.5% (22.1% – 41.3%) for patients treated in 1L, 16.4% (12.2% - 21.1%) for patients treated in 2L, and 12.2% (7.5% - 18.0%) for patients treated in 3L. The median number of cycles for 1L, 2L, and 3L were 5, 4, and 3, respectively. One-year OS increased as patients were able to receive more cycles of liposomal irinotecan. Patients who received at least 2 cycles of liposomal irinotecan (n = 551) had a one-year OS of 20.4% (16.8% - 24.2%). Among patients who received at least 4 cycles (n = 359) and at least 8 cycles (n = 170), the one-year OS estimates were 29.1% (24.0% - 34.3%) and 47.9% (39.7% - 55.7%), respectively. Conclusions: In this real-world cohort of patients with mPDAC treated with liposomal irinotecan, as expected, one-year OS increased as patients remained on therapy. Patients in this cohort were older, had more prior lines of therapy, worse ECOG PS, and similar exposure to treatment compared with patients in the registrational phase 3 NAPOLI-1 study. Among patients who received at least 4 cycles of liposomal irinotecan, one-year OS (29%) was similar to both the intent-to-treat (25%) and per protocol treated patient populations in the NAPOLI-1 trial (34%). Further studies are needed to understand the predictors of long-term survival among patients with mPDAC.

An Open–Label, Randomized, Multi–Center Study Comparing the Sequence of High Dose Aldesleukin (Interleukin–2) and Ipilimumab (Yervoy) in Patients with Metastatic Melanoma

ABSTRACT Combination immunotherapy with sequential administration may enhance metastatic melanoma (MM) patients with long-term disease control. High Dose Aldesleukin/Recombinant Interleukin-2 (HD rIL-2) and ipilimumab (IPI) offer complementary mechanisms against MM. This phase IV study assessed the sequenced use of HD rIL-2 and IPI in MM patients. Eligible Stage IV MM patients were randomized to treatment with either two courses of HD rIL-2(600,000 IU/kg) followed by four doses of IPI 3 mg/kg or vice-versa. The primary objective was to compare one-year overall survival (OS) with historical control (46%, Hodi et al., NEJM 2010). Secondary objectives were 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) profile. Evaluable Population (EP) included patients who received at least 50% of planned treatment with each drug. Thirteen and 16 patients were randomized to receive HD rIL-2 first, and IPI first, respectively. One-year OS rate was 75% for intention to treat population. Eighteen patients were included in EP, 8 in HD rIL-2, 10 in IPI first arm. In EP, 1-year OS, PFS and ORR rates were 87%, 68%, and 50%, respectively. The frequency of AEs was similar in both arms with 13 patients experiencing Grade 3 or higher AEs, 3 resulting in the end of study participation. There was one HD rIL-2-related death, from cerebral hemorrhage due to thrombocytopenia. In this study with small sample size, HD rIL-2 and IPI were safe to administer sequentially in MM patients and showed more than additive effects. 1-year OS was superior to that of IPI alone from historical studies.