Received Induction Therapy Research Articles

Different prognosis according to treatment in patients with acute promyelocytic leukemia: How the outcome changed over time.

A comprehensive analysis of 220 patients diagnosed with APL between 1993 and 2022 is here reported. Overall, 214 patients (97.2%) received induction therapy. Complete response (CR) was achieved in 97.4%, 100%, 100%, and 27% of patients treated with AIDA protocol, AIDA + Ara-C, ATRA + ATO, and ATRA monotherapy, respectively. Molecular complete response (CRMRD-) was achieved in 96.8% cases, and 142 patients proceeded to maintenance therapy. Overall, the 3-year and 5-year overall survival (OS) rates were 80.8% (95% CI, 78.1-83.5) and 79.1% (95% CI, 76.4-81.8), respectively. Considering only patients who completed induction and maintenance therapy, the 5-year OS rates were 82.1% (95% CI, 77.5-86.7) for the AIDA0493 cohort, 87.5% (95% CI, 84.4-91.1) for the AIDA2000 cohort, and 100% for the APL0406 cohort (p = 0.044). Additionally, the disease-free survival (DFS) rates were 65.7% (95% CI, 60.4-70.9), 70% (95% CI, 65.8-75.2), and 95.1% (95% CI, 91.7-98.5) (p = 0.016), respectively. Among low and intermediate-risk patients, age > 70 years (p = 0.027) and relapse (p < 0.001) were significantly associated with reduced outcomes. This study contributes to the advancement of our understanding of APL treatment, underscoring the ongoing need for research to enhance outcomes and explore new therapeutic approaches and prognostic factors.

Intensive Oral Hygiene Interventions during Therapy of Acute Leukemia May Result in Detrimental Outcomes: A Randomized Clinical Trial

Objectives There are no standard guidelines on oro-dental care during induction therapy of acute leukemia (AL). This study aimed to assess the effect of intensive oral hygiene practice on oral mucositis, infection, and disease outcomes compared to standard clinical practice. Materials and Methods Newly diagnosed patients with AL were randomized to receive either standard oral hygiene protocol (group A, n = 92) or comprehensive oral hygiene protocol (group B, n = 91). In group A, the oral hygiene indexes were measured by the dentist at baseline and at the end of treatment. In group B, weekly monitoring of oral hygiene indexes by the dentist and interventions in the form of oral cavity inspection, probing for gum health, and use of a soft toothbrush and education on oral hygiene practices were carried out. Results The frequency of mucositis was higher in group B (60%) than in group A (40%; p = 0.09). There was no difference in the median Simplified Oral Hygiene Index (OHI-S; 0.5 vs. 0.6) and Silness and Loe plaque index (0.4 vs. 0.25) between the groups. The local (11 vs. 1%; p = 0.005) and systemic infection rate (82.2 vs. 65.2%; p = 0.009) were higher in group B than in group A. Conclusion This study failed to show the superiority of a comprehensive oral hygiene protocol compared to standard protocol in reducing oral mucositis in patients receiving induction therapy for AL. We hypothesize that frequent intervention in the oral cavity may lead to the dissemination of infection.

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

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. 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. 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. 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.

Utilization of allogeneic hematopoietic stem cell transplantation among patients with newly diagnosed acute myeloid leukemia in California: a population-based linked dataset study.

Acute myeloid leukemia (AML) often requires allogeneic hematopoietic cell transplantation (alloHCT) for cure, but historically alloHCT has been strikingly underutilized. Reasons for this remain uncertain at the population level. We examined alloHCT utilization over time and explored associations between demographic/healthcare factors and use of alloHCT by age group (AYA 15-39y, adult 40-64y, older adult 65-79y) using a linked dataset merging the Center for International Blood and Marrow Transplant Research, California Cancer Registry, and California Patient Discharge Database. Eligibility included patients newly diagnosed with AML in California between 2001-2016 who received induction therapy and had no prior HCT. Multivariable Fine-Gray regression analyses were fitted separately across age groups. Among 7,925 patients with AML, alloHCT utilization increased over time across all age groups; however, in the most recent time period studied (2011-2016), utilization within 2 years of diagnosis remained lowest in older adults (13%) relative to adults (41%) and AYAs (49%). Factors statistically significantly associated with lower alloHCT utilization: (1) AYAs: female sex, lower neighborhood socioeconomic status (nSES), uninsured or Indian Health Services (IHS) coverage; (2) adults: older age, male sex, non-Hispanic Black or Asian race and ethnicity, unmarried, lower nSES, uninsured or covered by Medicaid, Medicare, or IHS, higher comorbidity, and living 100+ miles from a transplant center; and (3) older adults: older age, Asian race, and unmarried. In conclusion, using a population-based linked dataset, we demonstrate that utilization of alloHCT among older patients newly diagnosed with AML remains low in California, and factors associated with utilization vary by age group.

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.

Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study

Background & AimsAcid secretion inhibitors are associated with hypergastrinemia, which can lead to gastric mucosal changes. Potassium-competitive acid blockers, such as vonoprazan, are more potent than proton pump inhibitors, but long-term safety data are lacking. MethodsIn this phase 4, randomized trial, patients with erosive esophagitis (EE) received induction therapy (once-daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once-daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). The primary endpoint was the proportion of patients with malignant epithelial cell alterations, parietal cell hyperplasia, foveolar hyperplasia, enterochromaffin-like (ECL) cell hyperplasia, and G-cell hyperplasia. ResultsOverall, 202/208 patients (vonoprazan n=139; lansoprazole n=69) achieved healed EE and received maintenance therapy. No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was one adenoma in each group. At week 260, more patients taking vonoprazan versus lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%); proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar. Median serum gastrin levels were higher with vonoprazan treatment versus lansoprazole (625 pg/mL vs 200 pg/mL). Incidences of adverse events were comparable for both treatments. ConclusionsThe exploratory VISION study assessed the safety profile of vonoprazan and lansoprazole over 5 years in Japanese patients with healed EE. While gastrin concentration, parietal cell hyperplasia and foveolar hyperplasia were higher in the vonoprazan group, there was no increased risk of malignant epithelial cell alterations and gastric NETs. (ClinicalTrials.gov, NCT02679508.)

Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial

Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma. In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at the MD Anderson Cancer Center. We excluded patients with evidence of ongoing transformation to aggressive lymphoma. During phase 1, 1000mg intravenous obinutuzumab was administered with three predefined levels of oral lenalidomide in a 3+3 dose escalation design to establish lenalidomide 20mg as the recommended phase 2 dose. During phase 2, patients received induction therapy with six 28-day cycles of lenalidomide 20mg with intravenous obinutuzumab 1000mg. In accordance with our prior experience with lenalidomide plus rituximab, patients who were responding to the combination could receive up to 6 additional cycles (up to 12 cycles in total) of combination therapy. Dosing of obinutuzumab was continued in all responding patients after cycle 6 every 2 months for a total of 30 months from the start of therapy. The decision of number of cycles of combination therapy beyond 6 was at discretion of the investigator and was included to allow individualisation of therapy to maximise response while minimising exposure. The co-primary objectives were to evaluate the safety and overall response, defined as the proportion of patients who achieved a complete or partial response in relapsed and refractory indolent non-Hodgkin lymphoma at the end of induction therapy, according to Cheson and colleagues (2007 criteria). The secondary endpoints were complete response after induction therapy and time to event endpoints including time to progression, progression free survival, and overall survival. Analyses were intent to treat in the efficacy cohort and per-treated in the safety population in all patients who received at least one dose of either investigational agent. This trial is registered with ClinicalTrials.gov, NCT01995669. Between June 03, 2014, and 07 March 2019, we completed planned enrolment, and 66 patients started therapy including 9 patients in phase 1 and 57 patients in phase 2. All patients were evaluated for safety and the 60 patients treated at the recommended phase 2 dose of lenalidomide 20mg were evaluable for activity. Grade 3-4 haematological toxicities included neutropenia 21% (14/66) and thrombocytopenia 11% (7/66) with no cases of febrile neutropenia. Grade 3-4 non-haematological toxicities included lung infection 8% (5/66), fatigue 8% (5/66) and rash 6% (4/66). By Cheson 2007 criteria, 90% (54/60, 95% CI: 79-96) achieved an overall response at the end of induction meeting the prespecified activity endpoint. Complete responses were seen in 33% (20/60, 95% CI: 22-47) at the end of induction. Median progression free survival, time to progression and overall survival have not been reached after median follow-up of 41.7 months. Estimated 4-year progression free survival rates were 55% (95% CI: 42-73), time to progression of 56% (95% CI: 43-74) and overall survival of 84% (95% CI: 74-95). Our findings suggest that oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration. The study is limited by the lack of a control arm leading to cross-trial comparisons to evaluate activity. Future randomised trials comparing this regime to rituximab and lenalidomide are warranted. Genentech and an MD Anderson Core grant.

Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance.

Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM. Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m2) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years. The primary end point was undetectable measurable residual disease (uMRD) rate by next-generation flow after ASCT. Sustained uMRD 4 years after ASCT was the secondary end point. Between June 2015 and June 2017, 90 patients were included, and 31% met at least one SixtyLightchain MRI (SLiM)-hypercalcemia, renal impairment, anemia, bone disease (CRAB) criterion. After a median follow-up of 70.1 months, 3 months after ASCT, in the intention-to-treat population, 56 (62%) of 90 patients had uMRD, and 4 years later, it was sustained in 29 patients (31%). Five patients progressed to MM, and the 70-month progression rate was 94% (95% CI, 84 to 89). The presence of any SLiM CRAB criteria predicted progression to MM (four of the five patients; hazard ratio, 0.12; 95% CI, 0.14 to 1.13; P = .03). Thirty-six patients showed biochemical progression, and failure to achieve uMRD at the end of treatment predicted it. The 70-month overall survival was 92% (95% CI, 82 to 89). Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment-related death. Three second primary malignancies have been reported. Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT.

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%.

Interim results from a prospective multicenter phase II trial of stratified treatment of localized cervical esophageal squamous cell carcinoma induced by neoadjuvant immunotherapy plus chemotherapy (SCENIC trial).

e16089 Background: Definitive concurrent chemoradiotherapy (dCRT) is the standard treatment for cervical esophageal squamous cell cancer (CESCC). However, salvage esophagectomy poses significant technical challenges in dCRT failures, and optimizing patient selection for dCRT remains an unsolved concern. In this context, we propose a stratified screening strategy by incorporating induction immunochemotherapy, aiming to identify suitable candidates for organ-sparing dCRT and timely surgical treatment. Methods: This prospective multicenter interventional phase II study (ChiCTR2200057732) enrolled patients with clinical stage T2-4NanyM0 (AJCC TNM 8th) resectable CESCC. Eligible participants received induction therapy of intravenous PD-1 inhibitor tislelizumab (200mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1,8,15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles. Treatment response was evaluated 4 weeks after the completion of induction therapy, according to the criteria of the CROC trial: Grade 1, remarkable response (RR); Grade 2, limited partial response (LPR); and Grade 3, poor response (POR). Stratified patients would receive different follow-up treatments: dCRT was administered to RR patients, and radical surgery was performed in LPR and POR patients. Tislelizumab was maintained after dCRT in RR patients, and the postoperative adjuvant therapy was dependent on the doctors in the surgery groups. The primary endpoint was the 2-year event-free survival with a planned enrollment of 36 patients in this study. Results: From Jul 2022 to Jan 2024, 28 patients were enrolled. Of these, 22 patients completed the full two-cycle induction therapy and response evaluation. The response after induction immunochemotherapy were RR in 50.0% (11/22), LPR in 31.8% (7/22), and POR in 18.2% (4/22). All of the RR population underwent subsequent dCRT. Among 11 non-RR patients, only 7 cases received esophagectomy, other 4 selected dCRT according to their will. Up to Jan 2024, the median follow-up was 11.0 months (3.5-17.7), all of the RR patients with dCRT were in disease-free survival, 1 LPR and 1 POR patients received dCRT had progression in the primary lesion, and 4 patients underwent surgery had locoregional or distant recurrences. Overall, 24 patients (96%) had any-grade treatment-related adverse events with the most common being leukocytopenia. Four patients (16%) had adverse events of grade 3 or worse, and no treatment-related death occurred. Conclusions: The 1-year survival of RR followed by dCRT appears promising compared to historical data. The strategy of induction immunochemotherapy showed effective in identifying candidates suitable for dCRT in patients with resectable CESCC. Enrollment is ongoing. Clinical trial information: ChiCTR2200057732.

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 .

Frontline treatment with zanubrutinib plus rituximab (ZR) followed by short course R-DHAOx in patients with mantle cell lymphoma (MCL): Results of the phase II CHESS clinical trial.

7062 Background: Combining Bruton’s tyrosine kinase (BTK) inhibitor and rituximab showed favourable efficacy as first-line therapy for mantle cell lymphoma (MCL). Zanubrutinib, a next-generation, highly-selective BTK inhibitor, achieved promising antitumor activity in MCL. In this multicenter phase II trial (CHESS - chemo-less), we aimed to investigate the efficacy and toxicity of zanubrutinib plus rituximab (ZR) combination, followed by short course cytarabine-based chemotherapy, then zanubrutinib maintenance as frontline therapy for MCL (NCT04624958). Methods: Previously untreated MCL patients enrolled and received induction therapy of ZR until complete response (CR) or to a maximum of 12 cycles, and followed by 4 cycles of R-DHAOx regimen (rituximab, dexamethasone, cytarabine and oxaliplatin). Patients achieving CR after chemotherapy would receive maintenance therapy with zanubrutinib for a maximum of 1 year. The primary endpoint was CR rate after induction therapy with ZR regimen. Minimal residual disease (MRD) of bone marrow and peripheral blood were evaluated by flow cytometry. Results: From Oct 2020 to Nov 2023, a total of 42 patients were enrolled and the enrollment was finished. The median age was 57 years (IQR, 51-64). Stage III-IV accounted for 92.8%, and 42.8% were intermediate or high risk simplified MIPI. Thirty-four patients (81.0%) were classic histological subtype. The median cycle of ZR was 4 (range, 2-6). As of Jan 2024, among 37/42 patients with post-treatment PET evaluation, the best CR rate of ZR regimen was 91.9% (34/37), and 94.1% (32/34) obtained CR after 2-4 cycles. The bone marrow MRD negative CR rate was 92.0% (23/25). The other 5/42 patients were still receiving ZR treatment, and PET evaluation would be performed subsequently. Among 27 patients who finished chemotherapy and were evaluable for response, only one patient experienced disease progression. With a median follow up of 11.6 months, the 1-year progression-free survival and overall survival was 90.1% and 96.7%, respectively. Two patients died due to lymphoma (n=1) and COVID-19 (n=1). Grade 3-4 adverse events on ZR regimen were neutropenia (n=3), fatigue (n=2), and aminotransferase (n=1). During chemotherapy, grade 3-4 thrombocytopenia was observed in 75.8% of patients. Conclusions: Induction treatment with ZR followed by short-course R-DHAOx chemotherapy yielded promising antitumor efficacy. This strategy might reduce the toxicity of cytarabine-based chemotherapy without weakening the therapeutic efficacy. Clinical trial information: NCT04624958 . [Table: see text]

#2082 Effectiveness of a surveillance protocol and early mTORi conversion according to Urine BK viral load in Thai kidney transplant recipients

Abstract Background and Aims BK viral nephropathy (BKVN) is a crucial cause of early kidney allograft failure. Early detection and prompt treatment in the case of a high urine viral load might be more advantageous than waiting until BK viremia occurs. Data regarding outcome of BK infection based on adjustments of immunosuppression according to urine viral load is limited. Method A prospective cohort study of kidney transplant (KT) recipients at Siriraj Hospital, conducted between January 2015 and June 2020, involved monitoring urine BK viral load (RT-PCR) at 1, 2, 3, 6, 12, 18, and 24 months after KT. Determination of BK viremia and adjustments to immunosuppression were performed in patients with urine BK viral loads exceeding 1,000,000 copies/ml or demonstrating progressive increments in BK viruria. Initially, mycophenolate (MPA) dosage was reduced, and subsequently, conversion to mTOR inhibitors was considered for non-responsive cases. Data on the overall incidence and risk factors of BK viremia and/or BKVN were collected. Results Out of a total of 339 enrolled patients, 234 (69%) underwent deceased KT, and 49 (14.5%) received induction therapy with anti-thymocyte globulin. The incidence of BK viruria, viremia, and BKVN were 38.6% (131 patients), 9.7% (33 patients), and 4.1% (14 patients), respectively. The median time of occurrence for BK viruria and BKVN was 3 (IQR 1-12) and 4.5 (IQR 3–18) months after KT, respectively. Most BKVN cases (71.4%) developed within the first six months post KT. We did not find any significant risk factors associated with the occurrence of BK viremia or BKVN. Regarding the adjustment of immunosuppression, the initial reduction of MPA dosage was effective in 48 out of 92 patients (52.17%). In cases with an extremely high urine BK viral load or no response to MPA reduction, 46 patients received a change from MPA to everolimus, which was successful in 38 patients (82.6%). No graft loss due to BKVN was observed throughout the study. Conclusion The incidence of BK infection after KT in Thai recipients is high, comparable to western population. A surveillance protocol with urine BK viral load and early mTORi conversion is effective for prevention of allograft loss from BKVN.

#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 GS01-05: Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study

Abstract Background: Pembrolizumab (pembro) plus chemotherapy (chemo) showed statistically significant improvements in PFS and OS vs placebo + chemo in patients (pts) with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) whose tumors expressed PD-L1 with a combined positive score (CPS) ≥10 in the phase 3 KEYNOTE-355 study. Tolerable and effective maintenance regimens after induction therapy are needed to sustain clinical benefit. The PARP inhibitor olaparib is an established maintenance therapy for multiple platinum-sensitive tumor types and prior data suggest that PARP inhibitors combined with PD-1/PD-L1 inhibitors could provide an improved therapeutic effect. KEYLYNK-009 (NCT04191135) is a randomized open-label phase 2 study to evaluate the efficacy and safety of maintenance pembro + olaparib vs pembro + chemo in pts with locally recurrent inoperable or metastatic TNBC who had clinical benefit from induction with 1L pembro + platinum-based chemo. Methods: Eligible pts with measurable, locally recurrent inoperable or metastatic TNBC that had not been previously treated with chemo in the metastatic setting received induction therapy for up to 6 cycles of pembro 200 mg + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 and 8) every 3 wk (Q3W). Pts with complete response (CR), partial response (PR), or stable disease (SD) after 4-6 treatment cycles were randomized 1:1 to receive pembro 200 mg Q3W + olaparib 300 mg twice daily or pembro + chemo (continued induction regimen). Olaparib or chemo was continued until progression or unacceptable toxicity; pembro was continued for up to 35 cycles (including induction treatment), progression, or unacceptable toxicity. Pts were stratified by induction response (CR or PR vs SD, by RECIST v1.1), tumor PD-L1 status (CPS ≥1 vs CPS &amp;lt; 1), and tumor genomic status (tBRCAm vs tBRCAwt). Dual primary endpoints were PFS per RECIST v1.1 by BICR and OS from randomization in all pts. Secondary endpoints included PFS and OS from randomization in pts with PD-L1 CPS ≥10 tumors and in pts with tBRCAm, and safety. Results: Of the 460 pts who received induction therapy, 271 were randomly assigned to pembro + olaparib (n=135) or pembro + chemo (n=136). At the Dec 15, 2022 data cutoff, median follow-up was 17.2 mo. Maintenance pembro + olaparib did not significantly improve PFS or OS vs pembro + chemo after induction therapy (Table). Median PFS was longer with pembro + olaparib vs pembro + chemo in pts with tBRCAm, but not in pts with PD-L1 CPS ≥10 tumors; a similar trend was observed for OS (Table). In 268 treated pts, treatment-related AEs (TRAEs) occurred in 114 of 135 pts (84.4%) for pembro + olaparib and in 128 of 133 pts (96.2%) for pembro + chemo. Grade ≥3 TRAEs occurred in 44 pts (32.6%) for pembro + olaparib (0 deaths) and in 91 pts (68.4%) for pembro + chemo (2 [1.5%] deaths), with 12 (8.9%) vs 26 (19.5%) discontinuations for TRAEs, respectively. Conclusions: The primary endpoints of PFS and OS were not met in an unselected population of pts with advanced TNBC. However, directionally favorable improvements in PFS and OS were observed in pts with tBRCAm with pembro + olaparib vs pembro + chemo, representing a potential maintenance strategy. Further data are required to confirm this effect. No new safety signals were observed, and there were fewer TRAEs in the pembro + olaparib group vs the pembro + chemo group. PFS and OS were evaluated from the time of randomization. *Based on stratified Cox regression model with Efron’s method of tie-handling with treatment as a covariate. NR = not reached. Citation Format: Hope Rugo, Mark Robson, Seock-Ah Im, Florence Dalenc, Eduardo Yañez Ruiz, Young-Hyuck Im, Sergii Kulyk, Oleksandr Dudnichenko, Néstor Llinás-Quintero, Shigehira Saji, Yasuo Miyoshi, Nadia Harbeck, Li Fan, Jaime Mejia, Vassiliki Karantza, David Cescon. Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-05.

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.