Significant Difference In mOS Research Articles

Treating lung cancer in resource limited setting: Retrospective study from Armenia.

e20055 Background: Lung cancer (LC) is second most common cancer by incidence in Armenia. Every year approximately 800-900 new cases are diagnosed, from all cases 55.5% are in the 4th stage. Methods: We have collected data from three oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. In this retrospective hospital-based study the data of patients with LC who were treated at these three centers during the 01 Oct 2009 - 31 Dec 2023 period was collected․ Results: Four hundred and eighty-nine LC patients were involved in the final analysis. Male to female ratio was 6:1. From the all patients 10.6% were diagnosed at age ≤ 50, 79,6% of patients 50-70, and 9.6% ≥ 70 years. In 71.6% of all cases, LC was diagnosed in current or former smokers. Only 3% of patients were diagnosed in stage I, 9.8% in stage II, 44.8% in stage III, 41.1% in stage IV, and for 1.2% of patients' stage was unknown. From all cases 74% of patients had non small cell lung cancer (NSCLC), 22.7% small cell lung cancer (SCLC) and 3.3% had other histological types of lung cancer. Of all patients 63% are dead. The median overall survival (mOS) for all stages was 21 months for the entire cohort. Median OS was not reached for stage I ( > 100 months), was 61 months for stage II, 23 months for stage III, and 13 months for stage IV (p < 0,001). ALK mutation was checked in 22.7%, EGFR in 22%,ROS in 14.1%, KRAS in 11.2%, BRAF in 9.8% and of all patients. From all checked AKL was positive in 1.8%, EGFR in 19.4%, ROS in 2.8%, KRAS in 21.8%, BRAF in 8,3% and of cases. For patients with stage IV lung cancer (41.1%), we found a significant difference in mOS in those who received first line immunotherapy in combination with chemotherapy (19,4%) compared to those who received only chemotherapy (74.1%) (mOS: 24 months vs 11 months accordingly, p = 0.014). For stage I-III LC patients, those who received systematic therapy with cisplatin showed better overall survival than those who received systemic therapy with carboplatin (mOS 31 vs 25 months, p = 0.01), but for stage IV LC patients survival difference was not found (mOS 15 vs 12 months, p = 0.24). Conclusions: In Armenia, lung cancer is mostly diagnosed in the advanced stage where overall survival is approximately one year. In our study population, those who received immunotherapy in combination with chemotherapy showed doubled mOS, compared with only chemotherapy. In the nonmetastatic group, chemotherapy with cisplatin showed a significant increase in mOS compared with carboplatin.

Survival outcomes in primary orbital diffuse large B-cell lymphoma.

e19075 Background: Orbital diffuse large B-cell lymphoma is a rare entity accounts for less than 1% of all non-Hodgkin lymphoma cases. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with primary orbital DLBCL between 2004 and 2020. All patients aged ≥ 18 years diagnosed with primary orbital DLBLC were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 404 patients with primary orbital DLBCL. Out of whom 233 (58%) were females, 326 (81%) were White non-Hispanic, 29 (7%) were White Hispanic and 16 (4%) were African Americans. 113 (28%) received chemotherapy only, 76 (19%) received radiation only, 113 (28%) received chemoradiation, 79 (20%) did not receive any treatment and 23 (6%) had unknown treatment status. The median age at diagnosis was 71 years (range 28-90). The median follow-up time was 132 months (95%CI 117-147), the median overall survival (mOS) for the whole cohort was 110 months (95%CI 82-138). Among patients with known treatment status and vital status of last contact (N=381), patient who received chemoradiation had significantly better mOS compared to patients who received radiation only (169 vs 67 months, P=0.002), but there was no statistically significant difference in mOS between chemoradiation and chemotherapy only (169 vs 124 months, P=0.068) or between chemotherapy only and radiation only (124 vs 67 months, P=0.213). On multivariate analysis, older age and Charlson-Deyo score of 2 were associated with worse OS (HR 1.072 95%CI 1.055-1.089; P<0.001, HR 2.292 95%CI 1.099-4.778; P=0.027, respectively). Compared to no treatment, only chemoradiation was associated with better OS (HR 0.509 95%CI 0.332-0.778; P=0.002), whereas chemotherapy only and radiation only did not add a survival benefit (HR 0.909 95%CI 0.598-1.381; P=656 and HR 0.766 95%CI 0.496-1.185; P=0.231). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in primary orbital DLBCL compared to single treatment modality.

Efficacy of cytotoxic chemotherapy in recurrent/metastatic adenoid cystic carcinoma (ACC).

6111 Background: Despite aggressive local therapy, many ACC patients (~50%) develop recurrent and/or metastatic (R/M) disease. However, there is no standard of care or FDA-approved systemic therapy for this population. Based on small phase II trials, mostly including multiple salivary gland histologies, cytotoxic chemotherapy is recommended for symptomatic patients with high tumor burden, but its efficacy and impact on survival in R/M ACC remain unsubstantiated. Methods: A retrospective cohort study was conducted at MD Anderson Cancer Center with an institutional ACC database (N=769). Patients diagnosed with R/M ACC and treated with single-agent or combination palliative-intent chemotherapy were included. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST 1.1. Secondary endpoints were median overall survival (mOS) and progression-free survival (mPFS) on chemotherapy for the entire cohort and stratified by growth pattern (solid v non-solid), line of therapy (1 v >2), chemotherapy regimen, and stage at diagnosis (M0 v M1). Results: 48 out of 115 patients who received chemotherapy were evaluated for response per RECIST.Median age at diagnosis was 43.6 years. 56% were male, 79% had M0 stage at diagnosis, 67% had minor salivary gland primary tumors, 52% had solid growth pattern, 31% had non-solid growth pattern, and 54% received first-line chemotherapy. The most common regimens were Platinum/Vinorelbine (38%), Platinum/Taxane (27%) and CAP (15%).The ORR and DCR rates were 12.5% and 56.3% respectively; 6 had partial response, 21 had stable disease, and 21 had progressive disease. The ORR and DCR rates were 20% and 52% for solid and 6.7% and 73.3% for non-solid growth pattern, respectively. The mOS from diagnosis was 7 years (95% CI, 3.5-10.7). The mOS on chemotherapy was 16 months (95% CI, 10.8-24.5). There was a significant difference in mOS between solid and non-solid growth pattern (10.8 v 24.1 months, p=0.015), but not by line of therapy, regimen, or stage at diagnosis. The mPFS on chemotherapy was 4.3 months (95% CI, 2.8-6.3 months). There was a significant difference in mPFS between solid and non-solid growth pattern (4.0 v 7.3 months, p=0.018), but not by line of therapy, regimen, or stage at diagnosis. Conclusions: In this largest to date real-world data on chemotherapy in ACC, response and survival outcomes were lower than historical data. The efficacy of chemotherapy may vary by growth pattern and other patient and tumor factors, which requires further investigation. Given the low ORR and overall slow-growing disease pattern, tumor volumetrics may be better than RECIST to assess treatment benefit.

The genomic, transcriptomic, and immunologic landscape of TEM8 (ANTXR1) in small-cell lung cancer (SCLC).

3128 Background: The TEM8 receptor (coded by ANTXR1) plays several roles in oncogenesis. Novel oncolytic therapies, such as the SVV-01 virus, uniquely bind this protein in tumor histologies such as small-cell lung cancer (SCLC). Emerging pre-clinical data suggest that TEM8-targeting therapies may convert immunologically “cold” tumor microenvironments (TME) into “hot” milieu with greater responses to immune checkpoint inhibitors (ICIs). Methods: NextGen sequencing of DNA (592 genes or whole exome)/RNA (whole transcriptome) was performed on SCLC ( N=1404) submitted to Caris Life Sciences (Phoenix, AZ). Mutations were defined as pathogenic SNVs/indels. ANTXR1H and ANTXR1L samples included those with >75th and <25th percentile expression, respectively. PD-L1 expression (22c3; Positive (+):TPS ³1%) was assessed by IHC. High tumor mutational burden (TMB-H) was defined as ≥10 mutations per MB. Cell infiltration in the TME was estimated by QuantiSEQ. Gene expression profiles were analyzed for transcriptional signatures predictive of response to immunotherapy (T cell-inflamed) and MAPK pathway activation score (MPAS). Real-world median overall survival (mOS) was assessed from insurance claims data, and Kaplan-Meier estimates were calculated for molecularly defined subpopulations of patients. Mann-Whitney U and X2/Fisher-Exact tests were applied where appropriate, with P-values adjusted for multiple comparisons ( p<0.05). Results: No pathogenic mutations were significantly associated with ANTXR1H vs L tumors ( p>0.05 for all), along with no differences in the prevalence of TMB-H (28.6% vs 36.3%, p=1) or PDL1+ (45.0%: vs 35.0%, p=1). However, a greater proportion of B cells (6.53 % vs 5.12%, p<0.001), M1 (1.63% vs 0.37%, p<0.001) and M2 macrophages (3.40% vs 1.50%, p<0.001) were observed in ANTXR1H TME, which were more frequently classified as T cell-inflamed compared to ANTXR1L TME (23% vs 5%, p<0.001). ANTXR1H tumors also had higher MPAS compared to ANTXR1L (1.36 vs -1.86 arbitrary units, p<0.001). There was no significant difference in mOS between ANTXR1H vs L tumors (12.2 vs 10.5 months, HR: 0.95, p=0.678). Conclusions: Increased B cell, M1 and M2 macrophage infiltrates, and increased prevalence of T-cell inflamed tumors in ANTXR1H TME suggest that these patients with SCLC may respond preferentially to ICI. A Phase 1 trial incorporating SVV-01 along with ICI is underway. Prospective investigation of molecular associations and clinical outcomes related to ANTXR1 expression in SCLC is warranted.

Abemaciclib for the Treatment of HR+HER2- Metastatic Breast Cancer: An Institutional Experience.

(1) Background: Abemaciclib combined with endocrine therapy is a standard first- or later-line of treatment for HR+/HER2- metastatic breast cancer (MBC). The aim of this retrospective cohort study was to describe the outcomes of patients treated in a real-world setting, with particular focus on elderly patients. (2) Patients and methods: Patients treated with abemaciclib between November 2019 and February 2022 were included in the study. Data were collected from electronic medical records. The primary objective was to determine real-world progression-free survival (rwPFS), and secondary objectives included median overall survival (mOS) and safety. (3) Results: Analysis included 134 patients, with a median follow-up of 42 months. Median age was 62 years, with 29.9% aged 70+ years. A total of 51.5% of patients received abemaciclib in first-line, predominantly with aromatase inhibitor (68.1%). Median rwPFS was 21 in first-line and 20 months in the second-line, with no significant difference between treatment lines (HR 0.96; p = 0.88). Patients treated in the third- or later-line had a significantly shorter rwPFS, at 7 months (HR 1.48, p = 0.003). mOS was not reached in the first-line setting. For second- and third- or later-lines, mOS was 29 and 19 months, respectively. There was no significant difference in mOS between first- or second-line (HR 1.37, p = 0.36). In the 70+ group, median rwPFS was 15 months and mOS was 25 months with no significant difference compared to younger patients (rwPFS HR 1.1; p = 0.65; OS HR 1.4; p = 0.21). Most common adverse events (AEs) were diarrhoea (68.7%), anaemia (64.9%), and increased serum creatinine (63.4%). Grade 3/4 AEs were reported in 21.6% of patients. Dose reductions occurred in 30.6% of patients and were more frequent in patients 70+ (40%) compared to younger patients (28%); the difference was not significant (p = 0.22). At study cut-off, 64.9% of patients discontinued abemaciclib, primarily due to disease progression (73.5%). (4) Conclusions: Our study provides valuable insights into the effectiveness and safety of abemaciclib for the treatment of MBC. We observed comparable outcomes in terms of rwPFS and OS between the first two lines, suggesting consistent effectiveness across treatment lines. In addition, our findings suggest that older age (70+) does not significantly impact the effectiveness and tolerability of abemaciclib, although the careful monitoring and management of AEs are warranted.

Abstract 6293: Influence of prescription opioids and recreational cannabis use on efficacy outcomes and adverse events related to immune checkpoint inhibitors

Abstract Introduction: Opioids and cannabis possess immunomodulatory properties. However, the effect of opioid receptor activity on immune function is complicated, facilitated by several mechanisms and can lead to enhancement or inhibition. Similarly, the relation between cannabinoid ligands of diverse types and endocannabinoid receptors on various immune cells is complex. We hereby delineate the effect of prescription opioids and recreational cannabis use on immune-related adverse events (IRAEs) during immune checkpoint inhibitor (ICI) therapy in various cancers, as well as efficacy outcomes in advanced non-small cell lung cancer (aNSCLC). Methods: This is a retrospective cohort study of adult patients with advanced cancers who received ICI with or without chemotherapy for at least two months at an urban safety net hospital from January 2016 to June 2022. All patients, as well as a subset of patients with aNSCLC, were divided into two arms based on whether they were prescribed opioids during ICI therapy or not (OP vs. NO). Similarly, they were grouped based on whether they reported recreational cannabis use during ICI therapy (since initiation of therapy) or not (CA vs. NC). Incidence of IRAEs, median overall survival (mOS) and median progression-free survival (mPFS) calculated per RECIST 1.1 were the outcome variables. Multivariate logistic regression and alternative log-rank test were utilized for analysis with adjustments for demographics, insurance status, BMI, ECOG, PD-L1, TMB, smoking and concurrent chemotherapy. Results: 230 patients received ICI-based therapy; 47% were female, 34% were African American and 6.5% were Hispanic. There was no significant difference in the incidence of IRAEs between OP (n=144) and NO (n=86; p=0.225). However, CA (n=44) had higher IRAEs than NC (n=186) with an odds ratio estimate of 2.023 (X2=4.18, CI 1.03-3.97, p=0.04). Among 110 patients with aNSCLC, 46% were female. Patients with aNSCLC in the OP arm (n=69) had no significant difference in mOS (HR=1.34, CI 0.8-2.25, p=0.26) or mPFS (HR=1.21, CI 0.69-2.1, p=0.51) compared to patients in the NO arm (n=51). Similarly, the two arms CA (n=21) and NC (n=89) had no difference in mOS (HR:0.96, CI 0.5-1.83, p=0.89) or mPFS (HR:1.18, CI 0.61-2.29, p=0.63) for aNSCLC. Conclusion: Recreational cannabis use during ICI therapy increased the incidence of IRAEs. Prescription opioids and recreational cannabis use did not significantly affect survival outcomes for ICI in aNSCLC. Prescription opioid use also did not significantly influence the occurrence of IRAEs. This study suggests that recreational cannabis may need to be used with caution in this patient population due to its influence on IRAEs. On the other hand, opioids appear to be a safe option for pain management in these patients. Larger studies are warranted to shed more insight into the effect of these substances on ICI therapy. Citation Format: Himil Mahadevia, Benjamin Eidenschink, An-Lin Cheng, Atharva Desai, Stephanie Harry, Lara Kujtan. Influence of prescription opioids and recreational cannabis use on efficacy outcomes and adverse events related to immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6293.

Evaluation of Radiotherapy Efficacy and Prognostic Analysis for Solid and Cystic Brain Metastases.

Brain metastases (BMs) are commonly categorized into cystic and solid. However, the difference in the prognosis of patients with either cystic or solid BMs following radiotherapy remains poorly understood. We used a retrospective design to elucidate the disparities in survival between these two patient groups undergoing radiotherapy and to identify factors influencing the overall survival (OS) of patients with BMs. This retrospective study encompasses 212 patients diagnosed with BMs. We meticulously analyzed the clinical characteristics, radiation therapy modalities, and risk factors influencing the OS among these patients, categorized by BMs type, post-brain radiation therapy. A statistically significant difference in mOS was observed between the two cohorts (Solid vs Cystic: 23.1 vs 14.6months). Subgroup analysis unveiled distinctions in mOS, particularly in patients with EGFR-mutant lung adenocarcinoma (Solid vs Cystic: 23.1 vs 6.43months). The volume of BMs and the biological effective dose (BED) emerged as significantly prognostic factors for patients with cystic BMs. For patients with solid BMs, fraction dose, BED, and the number of BMs were identified as independent prognostic factors for survival. Brain radiotherapy shows superior survival benefits for lung cancer patients with solid BMs compared to those with cystic BMs, particularly in EGFR-mutant lung cancer. In particular, patients receiving BED ≥60Gy have a more favorable prognosis than those receiving BED <60Gy, regardless of the type of BM (solid or cystic) in lung cancer.

Brief Report: Real-World Toxicity and Survival of Combination Immunotherapy in Pleural Mesothelioma—RIOMeso

BackgroundAustralia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-year overall survival of 10%. First-line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate 743 trial, with supportive data from the later line single-arm MAPS2 trial. RIOMeso evaluates survival and toxicity of this regimen in real-world practice. MethodsDemographic and clinicopathologic data of Australian patients treated with ipilimumab and nivolumab in first- and subsequent-line settings for pleural mesothelioma were collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log-rank test. Toxicity was investigator assessed using Common Terminology Criteria for Adverse Events version 5.0. ResultsA total of 119 patients were identified from 11 centers. The median age was 72 years, 83% were male, 92% had Eastern Cooperative Oncology Group less than or equal to 1, 50% were past or current smokers, and 78% had known asbestos exposure. In addition, 50% were epithelioid, 19% sarcomatoid, 14% biphasic, and 17% unavailable. Ipilimumab and nivolumab were used first line in 75% of patients. Median overall survival (mOS) was 14.5 months (95% confidence interval [CI]: 13.0–not reached [NR]) for the entire cohort. For patients treated first line, mOS was 14.5 months (95% CI: 12.5–NR) and in second- or later-line patients was 15.4 months (95% CI: 11.2–NR). There was no statistically significant difference in mOS for epithelioid patients compared with nonepithelioid (19.1 mo [95% CI: 15.4–NR] versus 13.0 mo [95% CI: 9.7–NR], respectively, p = 0.064). Furthermore, 24% of the patients had a Common Terminology Criteria for Adverse Events grade greater than or equal to 3 adverse events, including three treatment-related deaths. Colitis was the most frequent adverse event. ConclusionsCombination immunotherapy in real-world practice has poorer survival outcomes and seems more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.

Examining Racial Disparities in Diffuse Large B-Cell Lymphoma (DLBCL) Outcomes within the Veterans Health Administration (VHA)

INTRODUCTION: The incidence of DLBCL in the United Sates is projected to increase to 32, 443 new cases per year by 2025. With increasing incidence and prevalence, DLBCL prognosis has improved significantly in the past decade through the addition of novel therapies such as new monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) therapy, antibody-drug conjugates, and most recently bispecific T-cell engagers. Despite these improvements, racial and ethnic disparities continue to impact outcomes in DLBCL patients (Flowers 2012). The purpose of this study was to assess racial and ethnic differences in DLBCL patients and outcomes within the VHA, an equal access system where confounding factors such as disease biology and socioeconomic status are more controlled giving us an opportunity to examine racial disparities. The aim of this study is to present a final analysis the final analysis of racial and ethnic differences in DLBCL patients within the VHA over a time span of 11 years. METHODS: Trained abstractors performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. Patients diagnosed with DLBCL were included. Patients were excluded if they had a diagnosis other than DLBCL, had incomplete records, or were diagnosed and treated outside the VHA. Data was collected on baseline patient demographics, disease characteristics, and treatment. Survival time was determined via electronic health record query on 1/4/2023. The study population was divided into non-Hispanic Black (NHB), non-Hispanic White (NHW), Hispanic (H), and other. Chi-squared tests were used to analyze the relationship between race and variables of interest. RESULTS: 3178 patients met inclusion criteria for analysis. Patients were predominantly male with a median age of 69 and presented primarily with advanced disease (Baseline Characteristics-Table 1). NHB were diagnosed at a younger median age (63 years) when compared to the NHW, H and other (69 years, P &amp;lt; 0.001). Patients in each subgroup presented with similar rates of stage I/II and III/IV disease with no statistically significant difference in stage at presentation amongst each racial subgroup (P=0.61). Of all the patients who received chemotherapy, the objective response (OR) rate was 79.2% with a complete response (CR) rate of 66.4%. The response rates were similar across the 4 subgroups with most patients achieving a CR after first-line therapy (P=0.74). There were no statistically significant differences in OR rates amongst subgroups (P = 0.95). Median overall survival (mOS) for the entire population was 69.6 months (95% CI = 65-75), with a mOS of 85.1 months (67-112), 85.9 months (60-112), 67.4 months (60-73), and 71.2 months (49-122) for NHB, H, NHW, and other patients respectively (Figure 1). There was no statistically significant difference in mOS amongst subgroups (P = 0.13). The 1-year, 3-year, and 5-year survival rates were also similar between subgroups (P=0.97, P= 0.39, P=0.32 respectively). CONCLUSION: This study represents one of the largest retrospective analyses of DLBCL in the VHA nationwide, highlighting that there is no statistically significant racial difference in DLBCL outcomes for patients treated within the VHA. Our study highlights the significance of equal access system and that disease biology and other social factors can be mitigated resulting in equal response to treatment and OS amongst all groups. Potential limitations of this study include using retrospective data on a predominantly white, male population that may not truly represent general DLBCL population data. The study period is mainly until 2021 with limited data on the accessibility of newer, novel treatments. With the development of newer, expensive treatments, especially Bispecific T Cell Engagers and CAR-T therapy, it is imperative to study utilizations of these novel treatments and study racial differences in this new treatment non-chemotherapy-based era.

Impact of Recent Advancements in Relapsed/Refractory Acute Myeloid Leukemia on Overall Survival in Clinical Practice

Introduction: The treatment landscape for relapsed or refractory acute myeloid leukemia (RR AML) is quickly evolving, guided by routine genetic profiling at diagnosis and relapse. In recent years, there has been a surge in FDA approvals for novel therapies, including venetoclax in combination with a hypomethylating agent (VEN + HMA), gilteritinib, ivosidenib, and enasidenib. Additionally, newer multi-agent combination chemotherapy regimens, such as fludarabine, cytarabine, idarubicin, and venetoclax (FLAG-Ida + VEN), have been increasingly used for RR disease. The year-by-year impact of the availability of these therapies on overall survival remains unclear. Methods: A cohort of 257 subsequent patients aged &amp;gt; 18 years with R/R AML treated at VCU Massey Comprehensive Cancer Center was retrospectively studied from 2015 to 2019. Only 2015-2019 were studied to avoid confounding from effects of the COVID-19 pandemic. Data was obtained from the medical record including cytogenetic and molecular profile, treatment regimens, allogeneic stem cell transplantation status (HCT), and survival. Disease was categorized by ELN 2022 genetic risk stratification. Median overall survival (mOS) was compared across individual calendar years using the Kaplan-Meier method. Categorical variables were analyzed using Fisher's exact test. Results: The median age of all patients with R/R AML was 61.4 years (range, 19.9-84.8) and median ECOG performance status was 1 (range, 0-4). The median Charlson Comorbidity Index was 4 (range, 0-14). Of the 248 patients for whom data on ELN 2022 genetic risk was available, 30 (12.1%) patients had ELN favorable risk disease, 65 (26.2%) had intermediate risk, and 151 (60.9%) had adverse risk disease. The median OS in 2015 was 5.8 months for all patients compared to 6.9 months in 2019 (p=0.38). When stratified by ELN risk category, patients with R/R favorable risk disease in 2019 had improved mOS compared to those in 2015 (mOS not reached vs. 7.1 months, respectively, HR 0.30 [95% CI 0.08-1.13], p=0.0400) (Fig. 1). There was no significant difference in mOS for the intermediate or adverse risk R/R AML cohorts over time. The proportions of patients with relapsed disease in 2019 who received alloSCT (39.2%) were numerically higher than in 2015 (26.3%), but were not statistically significant (p=0.259). Next, we studied relapsed/refractory therapeutic regimen usage over time. Coinciding with the approval of venetoclax, there was a marked increase in the percentage of patients who received a VEN + HMA beginning in 2018-2019, which corresponded to a decline in HMA monotherapy, as well as increased use of targeted therapeutics (Fig. 2). Conclusions: Prognosis for relapsed/refractory AML remains poor despite advances in novel therapeutics. While modest improvements in survival have been achieved, this is largely for ELN 2022 favorable-risk disease. Our work highlights the need for novel therapeutics aimed at those with relapsed or refractory disease. Our findings demonstrate reduced use of conventional chemotherapy in RR AML, with increased reliance on small molecule inhibitors and targeted therapies.

Hyperleukocytosis Does Not Present a Worse Prognosis in Acute Myeloid Leukemia (Non-APL) with Favorable Risk According to ELN-2022 Criteria: A Retrospective Study

Introduction: Acute myeloid leukemia (AML) with hyperleukocytosis, characterized by a white blood cell count ≥100,000/µL, is usually considered a subtype associated with poor prognosis. For AML patients with hyperleukocytosis, more aggressive treatment approaches, such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), are commonly considered. However, when favorable-risk AML accompanies hyperleukocytosis, it is unclear whether the risk level needs to be redefined. There is also no universally accepted treatment strategy for this subtype. We conducted a retrospective, single-center study to investigate the impact of hyperleukocytosis on the response and prognosis of favorable-risk AML according to ELN-2022 risk classification. Method: We retrospectively enrolled 217 favorable-risk AML patients, excluding acute promyelocytic leukemia (APL), treated at Zhejiang University School of Medicine's First Affiliated Hospital from October 1st, 2021, to April 30th, 2023. Some of them have been treated in other hospitals. The diagnosis, risk classification, and response evaluation were determined according to ELN-2022 criteria. Patients were divided into two groups: the hyperleukocytosis group (white blood cell count ≥100,000/µL) and the non-hyperleukocytosis group (white blood cell count &amp;lt;100,000/µL). We compare these two groups on the response rate after the induction chemotherapy, the median overall survival (mOS), and median disease-free survival (mDFS), then evaluate different treatments and other prognostic factors associated with outcomes. Statistical analyses were carried out using SPSS 24.0. The Kaplan-Meier method and log-rank test were used to assess and compare the survival outcomes. Univariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. A two-tailed P value &amp;lt;0.05 was considered statistically significant. Result: Totally 217 patients were enrolled. To balance the impact factors, 12 patients who received high-dose cytarabine were excluded from the non-hyperleukocytosis group. The cohort ready for analysis had 45 patients in the hyperleukocytosis group and 160 patients in the non-hyperleukocytosis group. Two groups had no significant differences in age; gender, FAB classification; platelet counts and hemoglobin level at initial diagnosis; co-existing intermediate/high-risk mutations according to 2022 ELN risk stratification; treated with high-dose cytarabine, or receiving bone marrow transplantation (all P＞0.05). The median follow-up time was 29.5 months, and 154 patients were still alive at the study endpoint. There were no significant differences in the composite complete remission (CRc) rates (73.3% vs. 79.3%, P= 0.389), mOS (65.0m vs. 56.0m, P= 0.574), and mDFS (54.0m vs. 35.0m, P= 0.855) between two groups. With high-dose cytarabine (2.0-3.0 g/m2 q12h X 3 days for at least three courses) as consolidation chemotherapy, the two groups had no significant difference in mOS (Not reached vs. Not reached, P=0.143) and mDFS (21.0m vs. 35.0, P= 0.352). In order to understand the impact of allo-HSCT on the hyperleukocytosis group, we divided this group into the allo-HSCT subgroup and the non-HSCT subgroup. After balancing on age, gender, presence of high-risk mutations, and MRD negativity after the first remission (all P&amp;gt;0.05), the mOS in the allo-HSCT subgroup (n=16) was significantly longer than the non-HSCT subgroup (n=16) (Not reached vs. 46.0m, P= 0.007). However, the mDFS had no significant difference between the two sub-groups (63.0m vs. 43.0m, P= 0.341). The univariate Cox proportional hazards regression analysis revealed that only age had a significant impact ( P= 0.01), all other factors had no significant effects, including hyperleukocytosis, gender, hemoglobin level, platelet count, intermediate/high-risk mutations, or bone marrow transplantation. Conclusion: In favorable-risk AML, hyperleukocytosis does not lead to an adverse prognosis. Received high-dose cytarabine as a consolidation therapy, favorable-risk AML patients with hyperleukocytosis do not have worse OS or DFS than those without hyperleukocytosis. Allo-HSCT may bring longer OS for hyperleukocytosis patients at favorable risk but may not bring longer DFS. Our results suggest favorable-risk AML patients with hyperleukocytosis can be managed equally as non-hyperleukocytosis patients.

The Presence of Ring Chromosomes in Patients with Myeloid Neoplasms Is Predictive of a Poor Outcome

Cytogenomic analysis is an important tool in the risk stratification of patients with hematologic malignancies. Complex chromosomal alterations are associated with a poor prognosis (Döhner et al., Blood 2022). Ring chromosomes (RC) are circular chromosomal structures associated with loss or gain/amplification of genetic material and are associated with poor prognosis in acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) (Rosenbaum et al., Human Path 2017). Due to their rarity, the impact of RC on response to therapy has not yet been well characterized. We further examined the significance of RC in AML, MDS and myeloproliferative neoplasms (MPN) by retrospectively analyzing records of patients identified to have RC and myeloid neoplasms at our institution between 2017 and 2023 and collected demographic, diagnostic, treatment, molecular, cytogenomic, and outcomes data. We identified 27 cases with RC with clinical data available for 25. Demographic and treatment details are described in Table 1. The most common chromosomes involved were r(11) and r(7), 6 and 4 cases respectively, followed by r(6) and r(19) with 2 cases each. The most frequently observed diagnosis was AML in 12 patients (48%) followed by MDS with 9 cases (36%) and MPN in 4 cases (16%). In 17 cases (68%) the RC was cytogenetically detected at diagnosis and was not observed in the context of prior therapy. Remarkably, mutations in TP53 were present in 14 cases (56%) and accompanied by loss of 17p (bi-allelic) in 7 cases (28%). The next most commonly observed gene mutations were in DNMT3A (7 cases), TET2 (4 cases) and ASXL1 (3 cases). In 11 cases (44%) the alterations in TP53 were not associated with prior therapy for other malignancies. The median time from prior chemotherapy to detection of the RC was 5.1 years (range 0.6 to 13.5 years). Chromothripsis (a single DNA catastrophic event resulting in extensive genomic rearrangements of one or a few chromosomes) as detected by CGH+SNP array and homogenous staining regions (autonomously replicating extra-chromosomal elements that are frequently associated with gene amplification) were observed in 3 patients each. RC were the sole genetic abnormality in 5 patients. A Kaplan-Meier analysis of median overall survival (mOS) in patients with AML and MDS with RC at diagnosis revealed that patients who received supportive care had significantly shorter mOS than patients who received hypomethylating agents (HMA), HMA/Venetoclax(VEN), or anthracycline-based chemotherapy (log rank test, p = 0.001). A significant difference in mOS between patients who received HMA alone versus HMA/VEN versus chemotherapy was not observed (11.4 vs 3.1 vs 7.3 months, p = 0.8) (Figure 1). Patients who received any of the therapies outlined above likewise demonstrated a significantly longer progression free survival (log rank test, p = 0.001). There was no effect on mOS for any of the other tested prognostic parameters, including the presence of a complex karyotype, TP53 allele status, or therapy-related neoplasm, nor for pair-wise interactions between those categories and first-line therapies (p &amp;gt; 0.05 for all tested associations). These data represent a large single-institution cohort of patients with RC and is the first to investigate the impact of therapy and molecular profiles in this population. We observed a high prevalence of TP53 mutations and loss of 17p, however we lacked longitudinal data to make causal inferences regarding the relationship between these abnormalities and ring formation. Of note, 68% of patients did not have prior exposure to therapy, and 36% of all patients lacked TP53 mutations or chromosomal p53 loss, indicating a high rate of de novo ring formation. This is a novel finding perhaps suggesting that inherent chromosomal instability characterizes these patients. Comparing response to type of therapy and outcomes of patients, we conclude that the mOS in patients with RC without therapy is significantly shortened compared with any of the therapeutic options described above, and that the addition of VEN to HMA did not positively influence mOS or PFS compared to HMA alone or chemotherapy in our cohort. Furthermore, the presence of a complex karyotype or a mutation and/or deletion of TP53 with a RC was not independently associated with inferior mOS, suggesting that the presence of a ring chromosome alone may be an important adverse risk factor in myeloid malignancies.

Comparing Arsenic-Containing Qinghuang Powder and Low-Intensity Chemotherapy in Elderly Patients with Acute Myeloid Leukemia.

To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients. Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups. The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01). QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.

Clinical and Genetic Analysis of Metastatic Prostate Cancer to the Central Nervous System: A Single-Institution Retrospective Experience.

Prostate cancer (PC) rarely metastasizes to the central nervous system (CNS). In this retrospective single-institution study at a tertiary cancer center, we aimed to evaluate the clinical and genetic characteristics of advanced PC patients with CNS metastases. Between January 2010 and March 2020, 12 out of 579 patients with extracranial metastatic PC were identified to have CNS metastases based on imaging, including six patients with brain metastases (BMs), five patients with dural metastases, and one unknown. These patients were followed up through March 2022. Clinical data were compared to the overall cohort of patients evaluated at our cancer center during that decade. Genetics information was also analyzed for the patients with available data via cell-free DNA (cfDNA) blood samples. Median time from development of extracranial metastatic disease to development of CNS metastases was 5.5 years (95% CI, 1.8-7.0). Median overall survival (mOS) from diagnosis of CNS metastases was 6.1 months (95% CI, 5.8-8.2). Notably, there was no significant difference in mOS after development of extracranial metastases in patients with CNS metastases (6.4 years; 95% CI, 4.6-7.9) compared to the patients without known CNS metastases (5.2 years; 95% CI, 4.6-5.7) (P=.91). For the cohort with CNS metastases, nine patients had germline testing and seven patients had somatic testing via cfDNA. PC patients with CNS metastases did not often die from a neurological cause. With advancing therapies, the overall prognosis of metastatic PC continues to improve, and CNS metastases will become more common.

First-line anti-EGFR or anti-VEGF therapy, tumour sidedness, and survival: Results from the South Australian (SA) Metastatic Colorectal Cancer (mCRC) Registry.

42 Background: The anti-EGFR monoclonal antibodies panitumumab (Pmab) and cetuximab (Cmab) and the anti-VEGF antibody bevacizumab (bev) have demonstrated clinical efficacy in mCRC in combination with first-line chemotherapy. Clinical and molecular characteristics, such as primary tumour sidedness, RAS, BRAF and MMR status are prognostic and predictive biomarkers for response to treatment. Our aim was to compare the survival and tumour characteristics of patients receiving first-line chemotherapy and antibody combinations using the SA mCRC Registry. Methods: This real-world registry has collected data from all patients diagnosed with mCRC in SA prospectively since 2006. We identified patients who had received first-line Pmab, Cmab or bev. Survival was analysed using the Kaplan-Meier method and log-rank test to compare outcomes based on primary tumour location. Results: Of the 5537 patients currently entered onto the registry, 1313 with RAS results available had received first-line anti-EGFR/VEGF antibodies and had colon tumour side recorded. The table summarises median overall survival (mOS) and patient characteristics. Survival was significantly shorter for those with right colon cancers (P &lt; 0.001). There were more high-grade (P &lt; 0.001), KRAS mutant (P = 0.004) and BRAF mutant (P = 0.036) tumours in those with right colon cancers, and a trend towards fewer curative liver resections (P = 0.059). There was no significant difference in mOS seen between Pmab, Cmab or bev for both left (P = 0.14) and right-sided (P = 0.88) primary tumours. Conclusions: There were more high-grade, BRAF and KRAS mutant patients with right colon tumours, and lower rates of liver resection, which may explain the significantly shorter mOS. The survival seen for Pmab and Cmab was almost identical for both right and left primary tumours. When comparing Pmab, Cmab and bev as first-line therapy, there was no significant difference in mOS for both left- and right-sided CRC. [Table: see text]

The Role of Corrected Dlco in Predicting Relapse and Mortality Post Autologous Hematopoietic Cell Transplantation in Multiple Myeloma

Introduction: Autologous Hematopoietic Cell Transplantation (AHCT) remains the standard of care for multiple myeloma (MM) patients who achieve at least a partial response to prior chemotherapy. Survival post AHCT is associated with disease risk and patient comorbidities, including lung diseases indicated by pulmonary function. The corrected diffusing capacity for carbon monoxide (DLCOc) is usually assessed in transplant candidates in order to determine AHCT eligibility, although precise DLCOc cut-offs are yet to be standardized. Recent studies suggested that a DLCOc ≤60% possesses a prognostic value in predicting relapse and mortality post AHCT. Hence, we aimed to validate the role of DLCOc ≤60% in predicting post-AHCT outcomes at our institution. Methods: We did a retrospective review of MM patients who underwent AHCT at Cleveland Clinic between January 1st, 2011 and January 15th 2021. The patients were categorized based on their corrected DLCO into two groups: DLCOc ≤60% and DLCOc >60% of the predicted value. Baseline characteristics, including patient, disease, and transplant factors were compared between the two groups. The collected data were analyzed using SPSS and GraphPad Prim by means of Chi square, ANOVA, and Kaplan Meier survival analysis. Results: A total of 466 patients with available DLCOc data were included in our study, of which 38 patients had a DLCOc ≤60% and 428 had a DLCOc >60% of the predicted value. Our cohort had a median follow up of 31.9 months post-AHCT. Patient and disease characteristics were similar between the 2 groups, including age (median 59.1 vs 60.3 years, P= 0.407), sex (Males 65.8 vs 58.2%, P=0.361), standard risk (81.5 vs 66.4%) and high risk (18.5 vs 33.6%) cytogenetic profiles (P=0.107), as well as history of smoking (23 vs 38.2%, P=0.1). In addition, both groups had a similar distribution across the International Staging System (ISS) stages (37.9, 37.9, 24.2% vs 38.3, 38.9, 22.8% for stages I, II and III, P= 0.987) and received similar preparative regimens (92.1, 7.9, 0% vs 96.3, 3, 0.7% for Melphalan 200 mg/m2, Melphalan 140 mg/m2 and Busulfan + Cyclophosphamide, P=0.25). Kaplan-Meier survival analysis showed that the DLCOc ≤60% group survived for a significantly shorter period with median overall survival (mOS) of 27.3 vs 91.7 months (P<0.0001) (Fig 1A). In addition, the DLCOc ≤60% group had earlier relapses with median progression free survival (mPFS) of 21.2 vs 38.7 months (P=0.0115) (Fig 1B). Subgroup analysis confirmed that mOS was significantly shorter in the DLCOc ≤60% group irrespective of relapse, with mOS of 25.4 vs 79.6 months (P<0.0001) in relapsed MM of DLCOc ≤60% (n=18) and DLCOc >60% (n=193) patients, respectively. Similarly, non-relapse survival was also shorter (medians unreached) in the non-relapsed DLCOc ≤60% group (n=20) compared to the non-relapsed DLCOc >60% group (n=235) (P<0.0001). When selecting patients of standard risk cytogenetics from both groups, the significant difference in mOS and mPFS was retained with mOS 51.7 vs unreached months (P<0.0001) and mPFS 21.2 vs 67.7 months (P=0.0051) for DLCOc ≤60% group (n=22) and DLCOc >60% (n=225), respectively. Likewise, matching for melphalan 200 mg/m2 regimen patients further maintained the remarkable gap in mOS 25.4 vs 91.7 months (P<0.0001) and mPFS 20 vs 40 months (P=0.0013) for DLCOc ≤60% group (n=35) and DLCOc >60% (n=413), respectively. Conclusion: The pre-AHCT DLCOc level possesses a useful prognostic value that can predict disease relapse as well as both relapse- and non-relapse related mortality post AHCT. This was demonstrated when using a cut-off value of ≤60% vs >60%. Our findings were supported by the fact that both groups had similar clinical and cytogenetic characteristics, thus reducing the risk of confounding effects. Our findings were also validated when controlling for cytogenetic risks and melphalan dosage. Large, prospective trials are warranted to determine whether DLCOc ≤60% can serve AHCT eligibility criterion. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Homologous recombination repair gene mutations as a predictive biomarker for immunotherapy in patients with advanced melanoma.

BackgroundNowadays, immunotherapy targeting immune checkpoint receptors is one of the cornerstones of systemic treatment in melanoma. Homologous recombination repair (HRR) is one of the DNA damage response (DDR) pathways, which has been proved to correlate with the efficacy of platinum-based chemotherapy, PARP inhibitor therapy, and immunotherapy in a variety of cancers. However, their predictive value of HRR remained unknown in patients with advanced melanoma.MethodsData of advanced melanoma patients from an independent cohort (Samstein2018) were used to analyze the correlation with immunogenic markers and the prognostic effect of HRR on immunotherapy, and another four cohorts (pooled cohort: Miao2018, Allen 2015, Hugo2016, and Synder2014) were used for validation. Immune infiltration cell scores analyzed by TCGA-SKCM cohort were used to explore potential mechanisms related to the immune microenvironment.ResultsCompared to patients with an HRR wild type (HRRwt), those with HRR mutations (HRRmut) in anti-CTLA-4-treated patients of the Samstein2018 cohort had higher tumor mutation burden (TMB; P = 0.0041) and longer median overall survival (mOS; P = 0.0094). In terms of results validation, it was also confirmed that the mOS (P = 0.0014) of HRRmut patients receiving anti-CTLA-4 therapy was significantly better than that of HRRwt patients in the pooled cohort, and objective response rates (ORR; P = 0.0053) were also found to be significant. However, there was no significant difference in mOS between HRRmut patients who received anti-PD-1/L1 therapy and HRRwt patients in either the discovery (Samstein2018 cohort, P = 0.94) or validation (pooled cohort, P = 0.96) set. Exploratory analysis found that although HRRmut patients showed no significant difference in mOS between anti-CTLA-4 and anti-PD-1/L1 therapy (P = 0.79), the mOS value of the anti-CTLA-4 therapy group (31.7 months) in HRRmut patients was numerically superior to the anti-PD-1/L1 therapy group (27.5 months). In contrast, the mOS of the anti-CTLA-4 therapy group was significantly lower than that of the anti-PD-1/L1 therapy group (12.4 vs. 32.0 months) in HRRwt patients. In addition, transcriptome profiling analysis revealed that the 29 (65.9%)-gene mutation of the HRR pathway associated with reshaping of the immunological microenvironment in melanoma.ConclusionsHRR mutations were associated with a higher TMB level, and better anti-CTLA-4 therapy outcomes. HRR may serve as an independent predictor of anti-CTLA-4 therapy efficacy in patients with advanced melanoma and their clinical value warrants further investigation.

P766: CLINICAL OUTCOMES IN PATIENTS WITH HIGHER-RISK MYELODYSPLASTIC SYNDROMES RECEIVING HYPOMETHYLATING AGENTS: A LARGE POPULATION-BASED ANALYSIS

Background: Myelodysplastic syndromes (MDS) are a spectrum of hematopoietic neoplasms characterized by variable degrees of cytopenias and risk of progression to acute myeloid leukemia (AML). Although the hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DEC) are widely used to treat higher-risk (HR)-MDS in the United States (US), questions remain about their longer-term clinical benefits. Aims: To understand the survival outcomes and progression-related events of patients (pts) treated with AZA or DEC for HR-MDS in the US. Methods: Older adults (≥66 years old) diagnosed with refractory anemia with excess blasts (RAEB), an established proxy for HR-MDS, between January 2009 and December 2017, were included from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The index date was date of HMA initiation. Pts who received AZA or DEC, had ≥12 months (mo) of continuous enrollment prior to the index date, and who did not receive a stem cell transplant (SCT) prior to the index date were included. Overall survival (OS) from the index date to death was estimated using Kaplan–Meier methodology. Baseline platelet and red blood cell (RBC) transfusion dependence (TD) were defined as ≥2 transfusion episodes in the 8 weeks prior to the index date; baseline transfusion use (TU) was defined as one transfusion episode in the 8 weeks prior to the index date. A competing risk analysis was used to assess the incidence of progression to AML, with death as the competing event. Results: Of 973 pts with HR-MDS treated with HMA, 75.8% received AZA and 24.2% received DEC. Median time from diagnosis to HMA initiation was 1.2 mo (interquartile range [IQR]: 0.6–2.6). Median treatment duration was 5.7 mo (IQR: 2.3–11.5) overall (5.8 mo [IQR: 2.6–11.8] for AZA and 5.0 mo [IQR: 1.9–11.0] for DEC). At baseline, 13.8% of pts had platelet TD/TU, 29.9% had RBC-TD and 27.0% had RBC-TU. Only 6.4% of pts received SCT during follow-up. Median follow-up from the index date until death or censoring was 13.8 mo (IQR: 6.2–25.3). Median OS (mOS) was 13.9 mo (95% confidence interval: 12.9–15.0). There was no significant difference in mOS for pts treated with AZA vs DEC (13.4 vs 15.2 mo, respectively; p=0.22). Pts with RBC-TD/TU had shorter mOS vs those with RBC-transfusion independence (TI) (10.7 vs 18.6 mo, respectively; p<0.0001). Similarly, pts with platelet TD/TU had shorter mOS vs those with platelet TI (8.4 vs 14.9 mo, respectively; p<0.0001). There were no statistically significant differences in OS by the route of AZA administration, insurance category, county metropolitan status, or county poverty level. Overall, 38.0% of HMA-treated pts progressed to AML; median time from HMA initiation to AML progression was 8.2 mo (IQR: 3.5–15.1). Cumulative incidences of AML and death were 25.7% and 30.7%, respectively, at Year 1 and 34.3% and 45.8%, respectively, at Year 2, with the rates of progression slowing over time. Summary/Conclusion: Compared with previously published literature from the SEER-Medicare database (Zeidan Br J Haematol 2016; mOS: 11 mo [AZA] and 12 mo [DEC] in pts diagnosed with HR-MDS between 2004 and 2011), pts with HR-MDS treated with HMA have improved mOS, but OS remains substantially worse vs the landmark AZA-001 trial (Fenaux Lancet Oncol 2009; mOS: 24.5 mo). The incidence of death and AML progression was highest in the first year after initiation of therapy. SCT rates remain very low among pts with HR-MDS, further emphasizing the urgent need for novel treatment options for pts with HR-MDS.

Characteristics, Management and Outcomes of Patients with Intravascular Lymphoma: A Mayo Clinic Experience

Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL.Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method.Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was <2 in 66%.The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse.Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (>30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29].Conclusion:1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected.2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations.3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions.4.Overall prognosis in the literature was poor with most patients surviving <1 year. Our cohort has mOS of 57 months. The reason(s) for better survival in our cohort could not be definitively determined.5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size.6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL.7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. [Display omitted] DisclosuresNowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

Outcome with Hypomethylating Agent and Venetoclax Combination in Patients with Chronic Myelomonocytic Leukemia

Outcome with Hypomethylating Agent and Venetoclax Combination in Patients with Chronic Myelomonocytic Leukemia