Patients Received Induction Therapy Research Articles

Risk Factor for Rash in Patients Receiving Cytarabine and Idarubicin Induction Therapy for Acute Myeloid Leukemia

Background/Aim: Rash is a common adverse event (AE) observed during cytarabine and idarubicin induction therapy in patients with acute myeloid leukemia (AML). Previous studies have highlighted the challenge in predicting the onset and duration of rash. This study aimed to determine the factors that affect the onset of rash in patients receiving induction therapy for AML. Patients and Methods: This retrospective study involved 97 patients with AML who received induction chemotherapy with cytarabine and idarubicin at the Department of Hematology, Kyushu University Hospital between January 2008 and June 2022. The factors associated with rash were identified through a multivariate stepwise logistic regression analysis. Subsequently, the patient’s characteristics were compared between those with risk factors and those without risk factors using a matched pair analysis. Results: Pre-existing leukopenia [odds ratio (OR)=3.294; 95% confidence interval (CI)=1.272-8.531] and good performance status (PS=0) (OR=2.717; 95%CI=1.087-6.792) were significant risk factors for rash development. Conversely, the matched pair analysis indicated that patients with pre-existing leukopenia, excluding those with a PS score of 0, exhibited a significantly (p=0.015) higher incidence of rash than those without it. Conclusion: Both multivariate logistic regression analysis and matched pair analysis identified pre-existing leukopenia as a primary risk factor for rash development associated with cytarabine and idarubicin chemotherapy.

Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19]years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.

Utilization of Discharge Checklist and Improved Education Reduces Hospital Readmission Rates in Childhood Leukemia Patients Receiving Induction Therapy.

The aim is to identify preventable cause for hospital readmissions during induction and implement interventions to decreased preventable treatment-associated complications. Multiple factors contribute to patients with acute lymphoblastic leukemia (ALL) requiring readmissions during induction. A dashboard monitored features of newly diagnosed patients with ALL. Readmission causes were stratified as preventable, possibly preventable, or unpreventable. A discharge checklist, including standardized education, and change of discharge date were implemented. Initially, there were 57 hospital readmissions of 98 patients (9 intensive care unit admissions and 2 deaths). Sixteen preventable (28.1%) and 32 unpreventable (56.1%) readmissions. After the interventions were initiated, including improved education, discharge checklist utilization, and standardized discharge date, there were 23 readmissions (78.3% were unpreventable, 6 intensive care unit admissions). Intervention implementation reduced readmission rates of induction patients with ALL by 20%.

Phase II study of multidisciplinary therapy combined with pembrolizumab for patients with synchronous oligometastatic non-small cell lung cancer TRAP-OLIGO study (WJOG11118L): Feasibility analysis of induction therapy and local ablative therapy.

8564 Background: Several clinical trials have shown that local ablative therapy (LAT) to all sites of the disease might provide survival benefit for patients with oligometastatic non-small cell lung cancer (NSCLC). Few studies have evaluated feasibility of multiciliary therapy combined immune-checkpoint inhibitor plus chemotherapy with LAT to all sites of disease. Methods: This multicenter, single-arm, phase II trial enrolled untreated patients with stage IV NSCLC who had 3 or fewer metastatic lesions. All patients had received 2–4 cycles of a systemic treatment including pembrolizumab and platinum-doublet chemotherapy as induction therapy. LAT was administered to all residual lesions after induction therapy, followed by maintenance therapy including pembrolizumab. The primary endpoint is the progression-free survival (PFS) rate of 24 months from the date of initiation of LAT. The secondary endpoints are safety, response rate of induction therapy, PFS, overall survival, and proportion of implementation. The present analysis showed feasibility of induction therapy and LAT. Results: Between October 30, 2020, and August 12, 2022, 30 patients were enrolled. The number of metastases at diagnosis was one in 7 patients (7/30, 23%), two in 14 patients (14/30, 47%), and three in 9 patients (9/30, 30%). All patients received induction therapy, and the objective response rate was 21/30, 70% (95% confidence interval, 50% to 85%). Adverse events of grade 3/4 occurred in 21/30, 70%, including neutropenia (5/30, 17%), anemia (2/30, 7%), and thrombocytopenia (2/30, 7%). Seven patients did not receive planned LAT for the following reasons: disease progression (N=3), adverse events (N=2; pneumonitis grade 2, and hepatitis grade 3), sudden death (N=1), and one patient had proven stage III after induction therapy. Twenty-three patients (23/30, 77%) received planned LAT to all sites of residual disease. As LAT, five patients received surgery only, 12 patients received radiotherapy only, and 6 patients received both surgery and radiotherapy. Eighteen patients completed planned radiotherapy for 32 lesions (primary sites 22%, lymph node 25%, bone 25%, pulmonary metastasis 19%, brain 6% and adrenal 3%). Eleven patients received surgery (primary sites and lymph node) as LAT. Grade 3/4 adverse events during LAT occurred in 3 patients (3/23, 13%): rash (n=1), hypoxia (n=1) and CPK increased (n=1). There were no treatment-related deaths. Conclusions: Results of the TRAP-OLIGO study showed that multimodality treatment with platinum-based chemotherapy plus pembrolizumab and LAT had favorable implementation, and planned LAT was feasible in this population. Clinical trial information: jRCTs041200046 .

Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial, ALTER-G-001-cohort C.

e16304 Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without progressive disease (PD) and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to response (TTR), depth of response (DpR), radical resection rate for LMs, and safety. Results: As of November 30, 2023, 44 patients were enrolled in cohort C (32 PC, 6 GC, 5 BTC, and others), the median age was 63.5 years (34-74), 65.9% male, 93.2% ECOG-PS 1 and 56.8% had LMs only. The majority of the pancreatic cancer patients (90.6%) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 37 evaluable patients in cohort C, 14 had partial response (PR), 18 had stable disease (SD) and 15 SD with reduced tumor size. The confirmed ORR was 37.8%, DCR was 86.5%. Of 25 evaluable pancreatic cancer patients, confirmed ORR and DCR were 36% (9/25) and 88% (22/25) respectively. In patients with pancreatic cancer, all PRs with DpR ≥30% and DpR ≥50% were 6 (66.7%). According to the Kaplan-Meier method, the median DoR was 4.6 (95%CI, 2.89-NE) months and PFS was 5.8 (95%CI, 4.1-6.0) months. The median TTR was 1.6 (range, 1.2-3.5) months. 36 patients in cohort C had TRAEs and ≥ grade 3 TRAEs (45.5%) mainly included hypertension (11.4%), neutropenia (9.1%), and blood platelet decreased (9.1%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335 .

#1714 The treatment of antibody-mediated rejection in kidney transplantation with recent drugs: a network meta-analysis

Abstract Background and Aims The recent treatments for antibody-mediated rejection (AMR) have been carried out in a small number of controlled clinical trials and are based on limited data. In recent research on AMR treatment, new drugs targeting B cells, plasma cells, the complement system, and IL-6 have been gaining attention. Method Studies on antibody mediated rejection (AMR) treatment were divided into four groups:, 1) rituximab, 2 bortezomib, 3 eculizumab, and 4) tocilizumab. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2023.5. We performed direct and indirect network meta-analyses using Bayesian models and ranked different AMR treatment method using a generation mixed treatment comparison (GeMTC) and Stata version 13. The outcomes included patient survival, graft failure, and bacterial and viral infections Results This analysis included 21 clinical trials with a total of 1217 participants. We focused on graft failure events based on the use of four groups of medications when patients received induction therapy for AMR treatment. There was a lower tendency in graft failure rates in the bortezomib and tocilizumab groups (odds ratio [OR] 0.31, 95% CrI: 0.058-1.4 and OR 0.42, 95% CrI 0.012-7.4), while the eculizumab group showed a higher graft failure rate (OR 2.3, 95% CrI 0.26-31.0) compared to the rituximab using group. However, these study results were not statistically significant. Conclusion When looking at the study results, although not statistically significant, it was observed that bortezomib and tocilizumab, compared to rituximab, showed a tendency to reduce the incidence of graft failure after AMR occurrence. Although this study did not demonstrate statistical significance, it is believed that future research with increased enrollment and additional studies may help identify effective drugs for AMR treatment.

Abstract CT213: Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

Abstract Background Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without progressive disease (PD) and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to response (TTR), depth of response (DpR), radical resection rate for LMs, and safety. Results As of November 13, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 38 evaluable patients in cohort C, 16 had partial response (PR), 17 had stable disease (SD) and 14 SD with reduced tumor size. The ORR was 42.1%, DCR was 86.8%. Of 26 evaluable pancreatic cancer patients, ORR and DCR were 42.3% (11/26) and 88.5%(23/26) respectively. 11 PRs and 10 SD- were observed with the median depth of response (DpR) of 37.6%. According to the Kaplan-Meier method, the median DoR was 4.1 (95%CI, 3.5-4.6) months and PFS was 5.8 (95%CI, 5.2-6.3) months. The median TTR was 1.7 (range, 0.8-3.5) months. 39 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (53.7%) mainly included neutropenia (19.5%), white blood cell decreased (14.6%), and blood platelet decreased (9.8%). Conclusions Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335. Citation Format: Junwei Wu, Chenfei Zhou, Jun Yan, Zhengxiang Han, Chun Wang, Zhiquan Qin, Jinling Jiang, Chunbin Wang, Xinyu Tang, Lingjun Zhu, Jun Chen, Yong Mao, Xiaowei Wei, Chengfang Shangguan, Jun Zhang. Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT213.

The Role of Autologous Hematopoietic Stem Cell Transplantation in the Therapy of Systemic AL Amyloidosis

Aim. To assess the outcomes of autologous hematopoietic stem cell transplantation (auto-HSCT) in systemic AL Amyloidosis patients treated at the R.M. Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation.&#x0D; Materials &amp; Methods. In the period from 2005 to 2022, auto-HSCT was performed in 33 patients with systemic AL Amyloidosis. In 7 of them, auto-HSCT was not preceded by the induction therapy “upfront”. From 2012 all patients received induction therapy prior to transplantation. The median age of patients was 54 years (range 38–68 years); among them there were 17 women and 16 men.&#x0D; Results. The 3-year follow-up period showed hematological response rate of 76 % (95% confidence interval [95% CI] 50–90 %), heart response rate of 27 % (95% CI 6–55 %), renal response rate of 76 % (95% CI 41–93 %), and hepatic response rate of 26 % (95% CI 8–50 %). The 5-year overall (OS) and progression-free (PFS) survivals were 71 % (95% CI 49–85 %) and 53 % (95% CI 32–71 %), respectively. The OS parameters in the group with delayed auto-HSCT, i.e., after induction therapy, were better than in the “upfront” group: 82 % (95% CI 60–93 %) vs. 43 % (95% CI 10–73 %) (p = 0.03). The OS parameters were affected by health status (p = 0.03), reduced left ventricular ejection fraction &lt; 60 % (p = 0.006), stage of heart disease (p = 0.016), and stage III kidney disease (p = 0.007). The PFS parameters depended on ECOG performance status (p = 0.004) and stage of heart disease (p = 0.041).&#x0D; Conclusion. The presented data confirm the results of the studies emphasizing the importance of induction therapy prior to auto-HSCT in the treatment of systemic AL Amyloidosis. More stringent parameters of renal function, left ventricular ejection fraction, and ECOG performance status can be used as criteria for auto-HSCT eligibility. Reduced melphalan doses, as conditioning regimen, can be administered to patients with pronounced comorbidity.

Effect of Induction Therapy Dose on Survival in Abo-Incompatible Kidney Transplantation: A Network Meta-Analysis Using Recent Data

Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.

Long-Term Survival and Stable Disease in a Patient with Extensive-Stage Small-Cell Lung Cancer after Treatment with Carboplatin, Etoposide and Atezolizumab.

Survival beyond 2years is rare in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemotherapy alone. We describe a patient with ES-SCLC who was treated with carboplatin, etoposide and the programmed death-ligand 1 inhibitor atezolizumab in the IMpower133 study (ClinicalTrials.gov registration: NCT02763579) and who achieved exceptionally long-term survival. Treatment-naïve patients with ES-SCLC (n = 403) were included in the IMpower133 study, and the identified patient had been randomised to the investigational treatment arm, where patients received induction therapy with carboplatin and etoposide plus atezolizumab for four 21-day cycles, followed by ongoing maintenance therapy with atezolizumab. The patient had achieved a partial response after induction therapy, and then received seven cycles of atezolizumab maintenance therapy until immune-related toxicities necessitated discontinuation. The patient was alive with an ongoing response and excellent performance status more than 6years after starting treatment and 5years after discontinuing atezolizumab maintenance. In conclusion, this patient with ES-SCLC from the IMpower133 study is a rare example of ongoing survival more than 6years beyond diagnosis and the start of treatment with first-line atezolizumab. This demonstrates the potential durability of response with immunotherapy.

Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C.

653 Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 37 evaluable patients in cohort C, ORR and DCR were 45.9% and 86.5% (PR, n=17; SD, n=15, 12 SD had reduced tumor size). Of 25 evaluable pancreatic cancer patients, 12 had PR, 10 had SD, ORR and DCR were 48% and 88%. According to the Kaplan-Meier method, the median DoR was 4.2 months (95%CI, 1.7-6.6) and the median PFS was 5.5 months (95%CI, 4.7-6.3). 37 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (51.2%) mainly included neutropenia (19.5%), white blood cell decreased (12.2%), and blood platelet decreased (9.8%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335 .

Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Updated results from multi-cohort, multi-center phase II trial ALTER-G-001-cohort A.

112 Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs). The prognosis of CRC with unresectable LMs is poor, with a 5-year survival rate of less than 5%. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, etc.). In cohort A, CRC patients received induction therapy (6 cycles, q3w): anlotinib (12 mg, PO, QD, days 1-14), oxaliplatin (130 mg/m2, IV, day 1), capecitabine (850 mg/m2, PO, BID, days 1-14). Patients without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 45 patients were enrolled in cohort A, the median age was 67 years (35-75), 66.7% male, 91.1% ECOG-PS 1 and 60% had LMs only. After induction therapy, 8 patients received surgical resection. Currently, 13 patients are receiving induction therapy and 10 are undergoing maintenance therapy, with a maximum duration of treatment (DOT) of 13.7 months. Of 39 evaluable patients in cohort A, ORR and DCR were 48.7% and 97.4% (PR, n=19; SD, n=19, 16 SD had reduced tumor size). The median PFS was not reached. 36 patients had TEAEs and ≥ grade 3 TEAEs (33.3%) mainly included neutropenia (11.1%), hypertension (6.7%), and white blood cell decreased (6.7%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs CRC tumors. Clinical trial information: NCT05262335 .

Assessment of 2022 European Leukemianet Risk Classification System in FLT3-ITD Positive Real-World Cohort from China

Background: The 2017 European LeukemiaNet (ELN-2017) risk classification system updated AML guidelines in 2022, adjusted FLT3-ITD mutated patients without core binding factor (CBF) or adverse risk markers to intermediate risk groups, according to the clinical trial results of midostaurin on patients with FLT3-ITD not NPM1 mutation and MRD in treatment decisions. However, midostaurin is not approved in mainland china; many patients in China are unable to receive FLT3 inhibitor due to highly cost yet. Methods: We include newly diagnosed de novo AML patients at our center from January 2017 to December 2021, regardless of the further treatment received. Patients with acute promyelocytic leukemia and AML with other previous myeloid neoplasms were excluded. All patients were diagnosed according to 2016 World Health Organization (WHO) criteria. Clinical data, chromosome and next-generation sequencing (NGS) results, treatment regimen and date of survival were included. Results: 408 patients were diagnosed as de novo AML (excluding M3) in our center, 364 patients have available cytogenetic and NGS data to access ELN-2022 risk classification. 137 (37.7%), 141 (38.8%) and 83 (23.5%) patients are classified into ELN-2022 favorable, intermediate and adverse risk groups, respectively, the median age of all patients at diagnosis is 52. 37 (10.2%) patients have a change in ELN risk classification compared with ELN-2017. In ELN-2017 favorable risk group, 19 patients whose FLT3-ITD allelic ratio &amp;lt;50% with NPM1 mutation are reclassified to ELN-2022 intermediate risk; in ELN-2017 intermediate risk group, five patients with CEBPA monoallelic bZIP mutation are reclassified to ELN-2022 favorable risk, 10 patients with MR gene mutations are reclassified to adverse risk; in ELN-2017 adverse risk group, 3 patients with FLT3-ITD allelic ratio &amp;gt;50% are reclassified to ELN-2022 intermediate risk. 323 (89.0%) patients received induction therapy: 271 (74.6%) patients received cytarabine-based chemotherapy, 52 (14.3%) patients unfit for intensive chemotherapy received hypomethylating agents (HMA)-based therapy, while 36 (9.9%) patients only received best supportive care, mainly due to early death during hydroxyurea treatment or did not want any therapy due to potential treatment costs. 211 (58.1%) patients received complete remission (CR), with CR rates in the ELN-2022 favorable, intermediate and adverse groups of 74.4%, 53.1% and 40.0%, respectively (p&amp;lt;0.001). After a median follow-up of 36.9 months, the median overall survival (OS) is 27.6 months, 10.6 months and 4.7 months in the ELN-2022 favorable, intermediate and adverse risk groups, compared to 21.9 months, 10.6 months and 4.8 months in the corresponding ELN-2017 risk groups. Patients in the ELN-2022 favorable group have a significantly better OS than those in intermediate and adverse group (p=0.002 and p&amp;lt;0.001), while there are no statistical differences between the intermediate and adverse groups (p=0.11), not significant as ELN-2017 (p=0.046). (Figure.1) 61 patients with FLT3-ITD mutations without adverse prognostic markers are classified as ELN-2022 intermediated risk. Among these patients, only 9 received FLT3 inhibitors (gilteritinib or sorafenib) due to late approval of FLT3 inhibitors in China; the remaining 52 patients received chemotherapy alone: 40 have FLT3-ITD allelic ratio &amp;lt;50%, 12 have allelic ratio ≥50%. These patients unable to receive FLT3 inhibitor did not achieve the same survival outcomes as other ELN-2022 intermediate risk patients (FLT3-ITD allelic ratio &amp;lt;50% group vs. intermediate risk group, p=0.046; FLT3-ITD allelic ratio &amp;gt;50% group vs. intermediate risk group, p=0.021); instead, both FLT3 mutated groups have no survival difference compare to the ELN-2022 adverse risk group. Moreover, for the ELN-2022 intermediate risk group without FLT3-ITD mutated patients, we find statistical difference to ELN-2022 adverse risk group on overall survival (median OS 17.6 months vs. 4.6 months, p=0.029), which is not achieved when FLT3-ITD mutated patients is included. (Figure.2) Conclusion: our real-world clinical data show that the ELN-2022 risk classification system is not superior to the ELN-2017 version in classifying patients in our center. For patients with FLT3-ITD mutation but unable to receive FLT3 inhibitor, their risk classification and treatment therapy should be considered as adverse risk group.

A Retrospective Comparative Analysis of Intensive Vs. Non-Intensive Chemotherapy in Treatment Naïve Acute Myeloid Leukemia (AML) Patients in India

Background &amp; Significance: Acute Myeloid Leukemia (AML) is a hematological malignancy characterized by the rapid proliferation of abnormal myeloid cells. Intensive chemotherapy has been the main stay of therapy in young adults whereas Azacytidine and Venetoclax based therapy is preferred in older and unfit patients of AML. As per Indian Acute Leukemia Research Database of (INwARD) of the Hematology Cancer Consortium, 3+7 is the most commonly used intensive chemotherapy in India induction mortality (n=392) is 16.9% (range 6.1 - 43%). (1) Another Indian Study of acute leukemia (n=268), highlighted that 54% had baseline infections. Only 40% of infected patients received induction therapy as compared to 93% of non-infected patients. Venetoclax has improved outcomes in AML. There is an unmet need for protocols for younger patients who are unfit for 3+7 due to multi drug resistant baseline infections or ECOG ≥2 or organ dysfunction. Poor risk cytogenetics and mutations are associated poor response to intensive therapies. We did retrospective comparative analysis of overall outcomes in patients receiving intensive chemotherapy versus non-intensive chemotherapy in a tertiary care centre of North India Material &amp; Methods: We did a retrospective comparison of intensive chemotherapy 3+7/ FLAG based therapy versus Azacytidine and Venetoclax based therapy since 2019. Institutional electronic medical record software (PARAS) was utilized to identify patients. Type of therapy was decided as per physician discretion. Patients who were elderly (age &amp;gt;60 years), ECOG PS 2 or more, or clinic-radiological evidence of infection. Intensive therapy included received Inj. Daunorubicin 60 mg/m2 IV once daily for 3 days and Inj. Cytarabine 100 mg/m2 IV as a continuous infusion for 7 days. Or FLAG/VEN based therapy Inj. Fludarabine 30 mg/m2 IV once daily for 4 days, Cytarabine 1500 mg/m2 IV once daily for 4 days. Inj. Filgrastim (biosimilar)5 mcg/kg s/c once daily from day 1 to ANC &amp;gt; 500 cells/ μL. Non-Intensive therapy arm received Inj. Azacytidine @75mg/m2 for 7 days with Tab Venetoclax 100mg once a day for 7-14 days as per patient tolerance. Posaconazole was used as a anti-fungal prophylaxis. We recorded baseline characteristics, type of therapy, compared the tolerability and efficacy of both the regimens. We did survival analysis using Kaplan Meier Curves and statistical analysis using SPSS version 25. Results: Baseline Data is presented in Table 1, 69 patients received intensive chemotherapy and 58 patients received non-intensive therapy. Patient in the intensive therapy arm were younger and fit whereas patients were older in the non-intensive therapy arm. Post Induction bone marrow evaluation was done between day 28 to day 35 post therapy. CR rate was 78.2 per cent in Intensive therapy arm v/s 51.7 per cent in non-intensive therapy arm. Patients were stratified as per ELN risk category. Patients in the standard risk and intermediate risk groups did better in the intensive therapy arm but outcome did not differ in patients of poor risk ELN category patients. Fig:1 Non- intensive therapy was better tolerated with fewer grade 3 or more febrile neutropenia and fewer 3 rd line antibiotics lesser duration of stay. The decision between intensive and non-intensive chemotherapy should be carefully individualized, considering patient age, performance status, cytogenetic risk, and comorbidities. Conclusion: Our study re-affirms the role of intensive chemotherapy in younger and fitter patients, however in adverse risk ELN patients non-intensive therapy appears non inferior to intensive therapy

A Retrospective Study of Patient Characteristics, Treatment Patterns and Outcomes in Patients with Primary CNS Lymphoma

INTRODUCTION: Primary CNS lymphoma (PCNSL) is a rare lymphoma subtype. Treatment with whole brain radiotherapy (WBRT) resulted in high response rates but poor overall survival and modern therapy typically involves combination chemotherapy regimens that include rituximab and high dose methotrexate and, in some cases, followed by consolidative chemotherapy such as autologous stem cell transplantation (ASCT). However, there is no standard regimen, and the choice is institutional and/or physician preference. We performed a single institution retrospective study evaluating the outcomes of patients with PCNSL with focus on outcome stratified by POD24. METHODS: We performed a retrospective analysis of patients with PCNSL at Cleveland Clinic between January 1, 2010 to December 31, 2020, at the Cleveland Clinic. Patients were excluded if there was any evidence of disease outside of the CNS. Progression-free survival (PFS) and overall survival (OS) after diagnosis were estimated using the Kaplan-Meier method and compared by log rank test. OS was estimated for patients with an event within 24 months (POD24) from the time of this event to death or last follow up. RESULTS: Data from 80 consecutive eligible patients were analyzed with a median follow up of 44 months. The median age at diagnosis was 63 (range 24-87) and 55% were female. Only a small minority of patients were being treated with immunosuppressants at diagnosis (12%). Of the patients receiving induction therapy, 35% received R-MPV, 20% received R-HDMTX, 4% received HD-MTX alone, 4 % received WBRT as a frontline treatment. 16% of patients received no therapy. The overall response rate to induction therapy was 62% (56% CR and 6% PR). The majority of patients did not receive consolidation treatment (59%). Of those who did receive consolidative therapy, non-myeloablative high dose cytarabine was the most frequently used strategy. Thirty-six patients progressed (45%) and of these, the majority (67%) occurred within 24 months of starting therapy. For the entire cohort, the median PFS was 16 months, and the median OS was 32 months. The 1-year and 5-year OS rates were 66% and 34%, respectively. An ECOG performance status of 0 or 1 was associated with significantly improved PFS and OS (p &amp;lt; 0.0001 for both. Median OS after PD for patients with POD24 was 6 months [95% confidence interval (CI) 4-NA] with only 42% alive at 1 year. CONCLUSION: This large retrospective study evaluating all patients with B-cell NHL PCNSL with extended follow up shows that the majority of progressive events occur within 24 months and is associated with poor outcomes. Rituximab and polychemotherapy regimens are now favored over rituximab and methotrexate alone to improve response rates. Our data show that emphasis on strategies for consolidation such as high dose chemotherapy and autologous transplantation are needed to prevent progression.

Optimizing antimicrobial prophylaxis strategies in acute leukemia patients: Assessing the efficacy of fluconazole

Background Acute myeloid (AML) and promyelocytic (APL) leukemia patients are at high risk for infection and mortality. While guidance for infection prevention is provided by the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), each institution may vary in antimicrobial prophylaxis prescribing practices. The discrepancy may be explained by medication intolerance, cost, and low incidence of mold infections in leukemia patients. A recent meta-analysis demonstrated mortality benefits with the use of posaconazole, which was adopted by the NCCN. Despite known risks, it is unclear whether universal mold-active coverage is indicated for all AML and APL patients. Objective To assess the incidence of breakthrough infections in AML and APL patients. Methods This was a single-center, retrospective chart review of AML and APL patients receiving induction therapy at Baylor St Luke's Medical Center (BSLMC) between January 2019 and October 2021. The primary outcome assessed the incidence of breakthrough infections. Descriptive statistics were used to summarize the data. Results A total of 55 patients were included and 54 (98%) had prolonged neutropenia with a median duration of 30 days. Five patients (9.3%) experienced breakthrough infections during induction while 21 individuals (38.9%) during the follow-up period. Aspergillus infections occurred in three patients receiving nonmold coverage compared to none on mold-active agents (p = 1.0) with no statistical difference in mortality. Conclusion Despite the majority of patients not receiving mold-active prophylaxis, nonmold-active prophylaxis may be sufficient with consideration of low aspergillosis incidence.

Clinical features of blastic plasmacytoid dendritic neoplasm in Chile: report of 10 cases

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant tumor with a dismal prognosis, with isolated case reports in Chile. The BPDCN can present skin and bone marrow compromise, and its diagnosis is frequently confused with other pathologies. This study aimed to evaluate the clinical and immunophenotypical features of BPDCN in the Chilean population. We performed a retrospective study from 2013 to 2021 in clinical records of 2 public Chilean referral hospitals, including ten patients, 80% male, with a median age of 66 years (15-81). The most frequent initial referral diagnoses were T-cell lymphoma (4/10) and acute myeloblastic leukemia (3/10). Seven patients presented skin and bone marrow involvement; we found a lower frequency of adenopathies (5/10), splenomegaly (2/10), and hepatomegaly (2/10). The complete blood count revealed anemia and leukopenia, with blasts in 5/10. Nine patients received induction therapy. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was indicated in 8/10 cases with remission in 5/8, and 1 patient received HyerCVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone, methotrexate, cytarabine) and an allogeneic bone marrow transplant. The median survival was 10 months (95% CI 4.2-15.8 months) with 9/10 deaths. Relapse in the central nervous system was documented in 2 cases. Our study found that BPDCN, a rare pathology in the Chilean population, shows a similar clinical presentation compared to previous studies. It is susceptible to respond to initial systemic and intrathecal chemotherapy.

#5296 CYTOMEGALOVIRUS INFECTION AFTER COVID-19 IN KIDNEY TRANSPLANT RECIPIENTS: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Kidney transplant recipients (KTR) have adverse COVID-19 outcomes due to the immunosuppressed status and multiple comorbidities. Cytomegalovirus (CMV) is one of the most frequent opportunistic infections after kidney transplantation. However, data concerning its reactivation after COVID-19 is scarce. Herein, we present a single-center cohort of KRT presenting with CMV infection after COVID-19 and its clinical outcomes. Method Single-center cross-sectional study including 22 KTR with CMV viraemia detected by quantitative polymerase chain reaction up to 6 months after COVID-19, between 2020 and 2022. Demographic and clinical data were collected from the electronic records. Results A total of 22 KTR (13 male) were included with a mean age of 55.5±15.5 years and a median Charlson score of 4 (IQR 3-6). Median time after transplantation was 65 months (IQR 12.5-174.5; 3 KTR with &amp;lt;6 months) and only one patient had been submitted to living-donor transplantation. Eight patients received induction therapy with antithymocyte globulin (ATG). At transplantation time, CMV serologic status had been: 50% D+/R+, 13.6% D+/R- and 4.5% D-/R+. CMV infection prior to COVID-19 had been documented in 6 patients. Concerning COVID-19, severe or critical disease had been reported in 8 patients. Specific therapy had been used in 4 patients: 2 with remdesivir/baricitinib, one with remdesivir and one with molnupiravir. Moreover, immunosuppressive therapy had been adjusted in 11 patients, namely by withdrawing the antimetabolite and increasing steroids (7 patients). Median maximum steroid dose (expressed as equivalents of prednisone dose) had been 40 mg (IQR 20-40) and mean cumulative steroid dose had been 416±317 mg. CMV disease was documented in 8 patients (4 with gastrointestinal involvement) and the mean time of diagnosis after COVID-19 was 10±6 weeks. Maintenance immunosuppression included tacrolimus, antimetabolite and steroid in 12 patients; 6 patients had supratherapeutic levels of tacrolimus at CMV infection diagnosis. Median initial viraemia was 770 copies/mL (IQR 288-4106). Valganciclovir was used in 14 patients (one was already taking it as prophylaxis), ganciclovir in 4 patients and CMV enriched human intravenous immunoglobulin was used in one patient. Nine patients required hospitalization and 2 were transferred to an intensive care unit; one of these 2 patients died. Induction therapy with ATG, CMV serologic status at transplantation time, previous CMV infection, COVID-19 severity or supratherapeutic immunosuppressive drug levels were not associated with CMV infection severity or hospitalization. However, higher maximum steroid dose during COVID-19 was associated with CMV disease (p = 0.038), higher viraemia at diagnosis (p = 0.032) and hospitalization (p = 0.018). Conclusion CMV infection is a common and clinically relevant complication in KTR. Altered immunologic status after COVID-19 may predispose to this infection. In addition, immunosuppressive therapy adjustments, namely the increase in steroid dosing may be very relevant to favor reactivation of CMV. Larger studies are warranted, but careful monitoring could help identifying risk patients earlier and prophylaxis may be considered when increased corticosteroids are prescribed.

CD81 and Its Relationship to Treatment Response in Patients With Acute Myeloid Leukemia at a Hospital in Hanoi, Vietnam.

Acute myeloid leukemia (AML) has the proliferation of poorly differentiated immature myeloid cells. New studies on immune markers also consider them as one of the factors that affect the prognosis or the patient's ability to respond to drugs. Our study was designed to determine the rate of remission and mortality, and the ability to respond to drugs in newly diagnosed AML patients withpositive CD81. A total of 50 patients diagnosed with AML (excluding acute promyelocytic leukemia) underwent immunophenotyping analysis using flow cytometry. Following the initial diagnosis, the patients received induction therapy, followed by three cycles of consolidation therapy. The patients were then followed up for a period of six months. The treatment efficacy was assessed at two timepoints: on day 28 after the first chemotherapy course and on day 28 after the fourth chemotherapy course. Out of the 50 newly diagnosed AML patients, 40 (80%) were found to be CD81 positive. This CD81-positive group had a high mortality rate after the first course of chemotherapy (17.5%)and after the fourth course of chemotherapy(52.5%), while no patients died in the CD81-negative group. The CD81-positive group had a worse drug response rate with 22.5% and 18.2% in CD81 positive group versus 30% and 40% in the CD81-negative group achieving complete remission after the first course and fourth course, respectively. The CD81 immunological marker was found to be highly prevalent among AML patients in Vietnam. Overexpression of CD81 in patients with AML is associated with an unfavorable prognosis, characterized by higher mortality rates and poorer treatment response.

CRES3T: A single-arm confirmatory trial of S-1 plus cisplatin with concurrent radical-dose radiotherapy followed by surgery for superior sulcus tumor.

8514 Background: A multicenter, single-arm, confirmatory trial (CRES3T) was conducted to investigate the efficacy and safety of S-1 plus cisplatin and concurrent radical-dose thoracic radiotherapy (TRT) followed by surgery in patients with superior sulcus tumor (SST). To date, no clinical trials on radical-dose TRT in the induction setting for SST have been conducted. Methods: SST was defined as a tumor that directly invades the chest wall including the first rib or more cephalad, subclavian artery, or subclavian vein according to CT or MRI scans. Eligible patients were 20 to 75 years old and had pathologically proven non-small cell lung cancer, performance status of 0–1, and no history of prior treatment. The patients received induction therapy consisting of three cycles of S-1 plus cisplatin with concurrent TRT (66 Gy in 33 fractions) followed by surgery. S-1 was administered orally at 40 mg/m2 twice per day, on days 1–14 along with an intravenous infusion of cisplatin (60 mg/m2) on day 1. The treatment cycles were repeated every four weeks. The primary endpoint was the 3-year overall survival (OS) rate, and key secondary endpoints included progression-free survival (PFS) rate, objective response rate (ORR), pathological complete remission (pCR) rate, and toxicity. Results: Between June 2014 and March 2019, 61 patients registered and received induction therapy. Pathological diagnoses were 30 adenocarcinoma, 20 squamous cell carcinoma, and 11 others. Radiologically diagnosed tumor invasion sites were the chest wall (n=57), subclavian artery (n=18), and subclavian vein (n=10). One patient with distant metastasis that manifested after starting induction therapy was removed from this study. Forty-nine patients underwent lobectomy and resection of the involved sites. The complete resection rate was 98% (48/49). Median follow-up time was 54 months. The 3-year OS and PFS rates were 73% (95% CI: 60–83%) and 53% (95% CI: 40–65%), respectively. The ORR and pCR rate were 42% (25/60, 95% CI: 29–54%) and 33% (16/49, 95% CI: 20–46%), respectively. Grade (G) 3 or 4 toxicities during induction therapy included neutropenia (28%), anemia (13%), thrombocytopenia (5%), and hyponatremia (8%). Two (3%) cases of pneumonia resulted in death. G3 surgical complications such as supraventricular arrhythmia, chylothorax, pleural effusion, pneumonia, mediastinitis, wound infection, and arm neuropathy developed in one (2%) patient each. One (2%) cardiac arrest on postoperative day 3 resulted in death. Conclusions: CRES3T demonstrated that induction therapy using S-1 plus cisplatin and concurrent radical-dose TRT followed by surgery was safe and effective in treating SST. Therefore, this strategy is potentially a new standard treatment for SST. (UMIN: 000014386, jRCT: s031180401.). Clinical trial information: UMIN000014386 .