Common Treatment Regimen Research Articles

Efficacy of CARVYKTI in CARTITUDE-4 versus other conventional treatment regimens for lenalidomide-refractory multiple myeloma using inverse probability of treatment weighting.

Aim: The phase III randomized controlled trial (RCT) CARTITUDE-4 (NCT04181827) demonstrated superiority of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) over daratumumab, pomalidomide and dexamethasone (DPd) and pomalidomide, bortezomib and dexamethasone (PVd) for relapsed/refractory multiple myeloma (RRMM) patients who have received one to three prior line(s) of therapy (LOT[s]) including an immunomodulatory agent and a proteasome inhibitor, and are refractory to lenalidomide. These analyses estimate the relative efficacy between cilta-cel and other common treatment regimens, for which no direct comparative evidence is available. Materials & methods: Patient data were available from the CARTITUDE-4, CASTOR, CANDOR and APOLLO RCTs. Imbalances between cohorts on key patient characteristics were adjusted for using inverse probability of treatment weighting (IPTW). Relative efficacies were estimated with response rate ratios (RRs) and 95% confidence intervals (CIs) for overall response rate (ORR), very good partial response or better rate (≥VGPR) and complete response or better rate (≥CR), and with hazard ratios (HRs) and 95% CIs for progression-free survival (PFS). Sensitivity analyses using different analytical methods and additional covariates were explored. Results: Key characteristics were well balanced across cohorts after IPTW. Cilta-cel showed statistically significant benefit in PFS (HRs: 0.11-0.51), ≥VGPR (RRs: 1.51-5.13) and ≥CR (RRs: 2.90-35.24) versus all comparators, and statistically significant improvements in ORR over most comparator regimens (RRs: 1.22-1.90). Results were consistent across sensitivity analyses. Conclusion: Cilta-cel demonstrated benefit over other common treatment regimens, highlighting its potential to become a new standard of care option for lenalidomide-refractory RRMM patients with one to three prior LOT(s). These comparisons help to demonstrate the improved efficacy of cilta-cel in countries where the standard of care may differ from DPd/PVd.

Advancing Cancer Care Infrastructure in Cambodia: Summary of the First 100 Patients with Cervical Cancer Treated at the National Cancer Centre

Background: Cervical cancer is Cambodia’s leading cause of female malignancy in both incidence and mortality. Cambodia’s first dedicated multidisciplinary cancer center, the National Cancer Centre (NCC), opened in January 2018 in Phnom Penh, and serves as the main public referral center for the region. Methods: This cross-sectional study retrospectively reviewed the care experience of the first 100 patients with cervical cancer treated at the NCC to collect demographic, diagnostic, and treatment characteristics. Results: The most common FIGO Stage was IIB (T2bN0M0) (n = 17). Squamous cell carcinoma represented 85% of cases. Definitive-intent therapy was recommended for 65 patients; neoadjuvant chemotherapy followed by external beam radiotherapy (EBRT) & tandem and ovoid (T&O) brachytherapy +/- concurrent cisplatin was the most common treatment regimen (n=23). Thirty-five patients presented with recurrent (n=22) or metastatic (n=13) disease and were treated with salvage/palliative intent; neoadjuvant chemotherapy followed by EBRT +/- concurrent cisplatin was the most common treatment regimen (n=10). Of the patients treated with definitive-intent treatment, 92% were prescribed an EBRT dose of 45 Gy in 25 fractions, and the median prescribed T&O brachytherapy dose was 28 Gy in 4 fractions. Mean cumulative EQD2 HR-CTV D90 dose was 91.8 Gy, or ~69-70 Gy to Point A, depending on planning technique. Follow-up data was limited to 27 patients; of the 14 patients whose follow-up period exceeded 1 year, 13 (93%) were alive and disease-free at their last assessment. Conclusion: With multidisciplinary partnership, the NCC has demonstrated that high quality complex cancer care can be delivered in a resource-constrained setting. This early sample of patients treated for cervical cancer is an initial step towards a better understanding of Cambodia’s patient population and an early snapshot of their cancer care delivery capacity.

Real-world treatment patterns and outcomes in relapsed/refractory multiple myeloma (1-3 prior lines): Flatiron database

AbstractIn the context of multiple myeloma (MM), early use of the immunomodulatory drug lenalidomide has led to an increased population of patients with lenalidomide-refractory MM in early-line settings, but their outcomes are not well characterized. Herein, we report treatment patterns, survival outcomes, prognostic variables, and attrition rates for patients with proteasome inhibitor–exposed, lenalidomide-refractory MM, treated with 1 to 3 prior lines of therapy (LOT). From 12 767 patients with MM in the Flatiron Health database between January 2016 and April 2022, 1455 met the inclusion criteria. The most common subsequent treatments were triplet combinations (41.6% of patients); daratumumab/pomalidomide/dexamethasone was the most common treatment regimen (13.2%). Median real-world progression-free survival (RW-PFS) and overall survival (OS) were 6.5 months and 44.4 months, respectively. RW-PFS was similar in patients with 1, 2, or 3 prior LOT. International Staging System stage III, Eastern Cooperative Oncology Group performance status of 1, hemoglobin <12 g/dL, high-risk cytogenetics, and refractoriness to anti-CD38 antibody at baseline were associated with worse RW-PFS and OS. Outcomes remained similar for patients who received National Comprehensive Cancer Network–preferred treatments and those who received treatments after 2020. In 561 patients with 1 prior LOT at inclusion, the cumulative attrition rate from LOT 2 to 5 was 85%, which included 25% patients who died and 60% with no further treatment. Patients with lenalidomide-refractory MM who have received 1 to 3 prior LOT have poor outcomes and progress rapidly through available therapies, highlighting the need for more effective treatments early in the disease course, before patients are lost to attrition.

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers.

Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0-42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0-4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease.

Real-world comparison of adherence to branded 20 mg dexamethasone tablets and generic 4 mg dexamethasone tablets among patients with multiple myeloma.

e19518 Background: Branded 20 mg dexamethasone tablets (BDex) is the first and only FDA-approved dexamethasone specifically indicated for the treatment of adult patients with multiple myeloma (MM) in combination with other anti-myeloma products. Generic oral dexamethasone is only available at lower dosages (e.g., 4 mg) despite the standard dexamethasone dosage for MM being 20 or 40 mg. The availability of 20 mg tablets would, therefore, reduce pill burden and assumably improve adherence in MM patients. The objective of this analysis was to quantify and compare adherence of BDex and generic 4 mg dexamethasone (GDex) among MM patients using real-world evidence. Methods: Using an open claims database, which included professional, hospital, and pharmacy claims for over 295 million individuals across the United States from 2015 to 2023, BDex and GDex users aged ≥18 years with MM were identified. Baseline summary statistics were generated and chi-squared and t-tests were performed comparing continuous and categorical variables respectively between the treatment cohorts. Treatment adherence was determined using a medication possession ratio for flexible time period (MPRF) given variable numbers of cycles across patients. MPRF was reported as both a continuous and binary measure (≥80%). Differences in MPRF were determined utilizing t-tests. Results: Between September 1, 2020 and June 30, 2023, 43 BDex and 3,775 GDex users meeting all study criteria, including ≥2 prescription claims, were identified. Overall, 30.8% were aged 18-64 years, 54.6% were male, 71.2% were insured through Medicare, and 20.3% were insured commercially. Bortezomib monotherapy, immunomodulatory agent monotherapy, and daratumumab and bortezomib were the most common treatment regimens (17.5%, 11.1%, 7.2%, respectively). Mean MPRF was significantly higher in BDex users compared to GDex overall (97.1% vs 89.5%, p &lt;0.001), among those 18-64 (98.7% vs 89.1%, p &lt;0.001), those with commercial insurance (99.9% vs 90.4%, p&lt;0.001), and those with Medicare (96.1% vs 89.6%, p=0.048). A significantly greater proportion of BDex users were considered adherent compared to GDex patients (95.3% vs 78.4%, p=0.007). This trend was seen across age and payer sub-cohorts, with significant differences seen in those with Medicare (96.0% vs 78.7%, p= 0.035). Conclusions: Adherence to BDex was greater than to GDex in this MM study population overall, and for age group and payer sub-cohorts. Given these findings, physicians may want to consider overall pill burden and regimen complexity when prescribing MM treatment for their patients.

Examining the antitumorigenic effects of Ruminococcus gnavus

Abstract Melanoma is one of the most commonly occurring cancers in the world, with increasing occurrence over the past several decades. Common treatment regimens for melanoma include immune checkpoint inhibitor (ICI) therapy, which enhances interferon-γ production in CD8 T cells (Tc1). Despite showing efficacy in some patients, a majority of melanoma patients are resistant to ICI therapy. Prior studies have demonstrated the ability of the gut microbiota to impact Tc1 antitumor responses and ICI therapy efficacy. In analyzing top gut bacteria enriched in ICI-responders, Ruminococcus gnavus (R. gnavus) is a commonly identified species. Here we demonstrate the tumor restraining properties of R. gnavus in subcutaneous, spontaneous, and metastatic cancer models. Further, gnotobiotic monocolonization experiments demonstrate the ability for this bacterium to restrain tumor growth independent of a complex microbiome. Analyzing the mechanism behind how R. gnavus causes melanoma growth suppression in our model, we have demonstrated requirements of bacterial viability and aryl hydrocarbon receptor (AHR) activation. Colonization with R. gnavus at various tumor timepoints was able to induce a significant Tc1 response locally in the tumor and systemically in lymphoid organs. Finally, we found R. gnavus colonization to facilitate ICI efficacy in our model. This study uncovers a potential mechanism of how a common ICI-response associated bacterium enhances ICI efficacy in melanoma.

Abstract 2542: Real-world validation of the PurIST classifier demonstrates enhanced therapy selection for pancreatic ductal adenocarcinoma (PDAC) patients

Abstract Background: PDAC is a particularly fatal condition lacking established biomarkers for the choice of first-line treatment (1L). The PurIST algorithm is a gene signature (Rashid et al. Clin. Cancer Res., 2020) that categorizes PDAC tumors into basal or classical molecular subtypes and has been previously validated in a patient cohort of advanced PDAC (N=258). In this post-hoc analysis study, we examine whether the PurIST subtypes can distinguish patients likely to respond to FOLFIRINOX (FFX) versus Gemcitabine + nab-paclitaxel (GnP). Methods: A cohort of de-identified PDAC patients was selected from the Tempus Oncology Database following an IRB-approved protocol. Inclusion criteria required no prior systemic treatment, a surgically unresectable/metastatic status, available RNA-sequencing data from primary or metastatic tissue, and the use of FFX or GnP as 1L systemic therapy with documented outcomes. RNA-sequencing was generated by the CAP/CLIA validated Tempus xR assay. The PurIST gene signature was applied to normalized gene expression values to classify samples into basal or classical subtypes. Univariate and multivariate Cox PH analyzes comparing overall survival (OS) with adjustment for delayed entry, between two common 1L treatment regimens, FFX and GnP, were performed for classical patients with an ECOG performance status of 0 or 1. Results: Application of the PurIST model to the PDAC cohort (N=258) resulted in 67% (N=173) labeled as classical, 23% (N=59) as basal, and the remainder as no-call. Amongst classical patients, 35% (N=61) had a known ECOG score of 0 or 1 and were retained for subsequent analysis. Within this subset, 37 were treated with FFX and 24 with GnP as 1L, with an overall median OS of 11.4 months (95% CI: 9.5-16.5) and a 12-month survival rate of 47.2%. A univariate Cox PH analysis showed that classical patients treated with FFX had a significantly longer OS time (HR (95% CI) = 2.32 (1.29-4.17)). This result remained significant in a multivariate Cox PH, adjusting for age and ECOG, (HR=2.5 (1.15-5.44)). Conclusion: In this real-world cohort of advanced PDAC patients, we showed that classical patients with low ECOG scores had superior OS with 1L FFX treatment compared to 1L GnP. These findings demonstrate the potential for PurIST to aid in optimal treatment selection for patients with advanced PDAC. Citation Format: Stephane Wenric, James M. Davison, John Guittar, Gregory M. Mayhew, Kirk Beebe, Alia Zander, Seung Won Hyun, Kyle Beauchamp, Michael V. Milburn, Vincent Chung, Tanios S. Bekaii-Saab, Charles M. Perou. Real-world validation of the PurIST classifier demonstrates enhanced therapy selection for pancreatic ductal adenocarcinoma (PDAC) patients [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 2542.

Real-World Treatment Patterns and Clinical Outcomes After Platinum-Doublet Chemotherapy and Immunotherapy in Metastatic Non-Small Cell Lung Cancer: A Multiregional Chart Review in the United States, Europe, and Japan.

To characterize treatment patterns and real-world clinical outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) who developed progression on an anti-PD-1/anti-PD-L1, herein referred to as anti-PD-(L)1, and platinum-doublet chemotherapy. Eligible oncologists/pulmonologists in the United States, Europe (France, Germany, and United Kingdom), and Japan completed electronic case report forms for patients with mNSCLC (no evidence of EGFR/ALK/ROS1 alterations). Eligible patients had disease progression on/after an anti-PD-(L)1 and platinum-doublet chemotherapy (received concurrently or sequentially), initiated a subsequent line of therapy (LOT) between 2017 and 2021, and had an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at this subsequent LOT initiation (index date). Overall survival (OS), time to treatment discontinuation (TTD), and real-world progression-free survival (rwPFS) after index were assessed using Kaplan-Meier analysis. Overall, 160 physicians (academic, 54.4%; community, 45.6%) provided deidentified data from 487 patient charts (United States, 141; Europe, 218; Japan, 128; at mNSCLC diagnosis: median age 66 years, 64.7% male, 81.3% nonsquamous, 86.2% de novo mNSCLC; at line of interest initiation: 86.0% ECOG 0-1, 39.6% liver metastases, 18.9% brain metastases, 79.1% smoking history). The most common treatment regimens upon progression after anti-PD-(L)1/platinum-doublet chemotherapy were nonplatinum chemotherapy (50.5%), nonplatinum chemotherapy plus vascular endothelial growth factor receptor inhibitor (12.9%), and platinum-doublet chemotherapy (6.6%). Median OS was 8.8 months (squamous, 7.8 months; nonsquamous, 9.5 months). Median TTD was 4.3 months (squamous, 4.1 months; nonsquamous, 4.3 months). Median rwPFS was 5.1 months (squamous, 4.6 months; nonsquamous, 5.4 months). In this multiregional, real-world analysis of pooled patient chart data, patients with mNSCLC who had disease progression after anti-PD-(L)1/platinum-doublet chemotherapy had poor clinical outcomes with various treatment regimens, demonstrating an unmet clinical need for effective options after failure on anti-PD-(L)1 and platinum-doublet chemotherapy treatments.

P504 Prevalence of gastrointestinal infections in ulcerative colitis patients assessed with QIASTAT-DX® GASTROINTESTINAL PANEL 2

Abstract Background In inflammatory bowel disease (IBD), an acute clinical flare may be due to either disease exacerbation or an enteric infection. Thus, it is recommended to exclude infections before escalating IBD therapy. In this setting, conventional tests identify only a minimal proportion of infections (i.e. 10%). Whether nucleic acid multiplex tests can expand the range of detected pathogens and increase the overall prevalence is still a matter of debate. Methods We performed a single-center transversal prospective study at Fondazione IRCCS Policlinico Ca’ Granda. Stool samples from consecutive ulcerative colitis (UC) patients experiencing a disease flare and a group of patients in clinical remission were enrolled between February and October 2023 and tested with QIAstat-Dx Gastrointestinal Panel 2 (Qiagen GmbH, Hilden, Germany) for simultaneous qualitative detection and identification of nucleic acids from multiple viruses, bacteria, and parasites. Clinically active disease was defined as a Partial Mayo Score (PMS) of ≥2. Results Overall, 85 UC patients were enrolled. Demographics and clinical features are displayed in Table 1. Median age was 42 (18-79), 52% were males. The two most common treatment regimens were mesalamine (54%) and biologic/small molecule treatment (35%). 66 (78%) patients were clinically active, while 19 (22%) were in remission. In the active group, median bowel movements were 5 (3-15), 58 (88%) patients had loose stool, 32 (49%) reported abdominal pain, 40 (61%) urgency, 10 (15%) overnight symptoms, 6 (9%) fever. Median PMS was 5 (2-8). Median hemoglobin was 13.8 (8.2-16.4) g/dL, fecal calprotectin 508 (&amp;lt;5-4980) ug/g. Prevalence of gastrointestinal infections with QIAstat-Dx was 30 vs. 10% (p=0.13) in active vs. remission group, respectively. The most common infections were: C.Difficile infection (CDI) (4 cases), Cytomegalovirus (CMV) (4 cases) and enteropathogenic E.Coli (EPEC) (4 cases). Regarding viral and E. Coli infections, clinical remission (PMS &amp;lt;2) occurred spontaneously. As for CMV, Campylobacter spp., and CDI, all patients except one achieved remission following specific antimicrobial treatment. In one patient CMV infection led to hospital admission (circulating CMV DNA 35,395 IU/mL). The remaining patient did not receive specific antiviral therapy since sigmoidoscopy only detected isolated CMV+ cells, and remission was achieved with UC treatment escalation. Conclusion In UC patients experiencing a clinical flare, prevalence of gastrointestinal infections with QIAstat-Dx® Gastrointestinal Panel 2 is numerically higher than patients in remission. Further studies are needed to investigate whether increased detection could influence the clinical outcomes of IBD patients and time and costs for the healthcare system.

Clinical characteristics and status of treatment of small-cell carcinoma of the ovary, hypercalcemic type in the Chinese population: a meta-analysis.

This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Risk factor analysis and nomogram construction of postoperative complications for patients with locally advanced gastric cancer who received neoadjuvant immunotherapy and chemotherapy.

The combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs. This study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured. In 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien-Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) >1.33, non-R0 resection, and body mass index (BMI) < 18.5 kg/m2 were independent risk factors for overall POCs (p < 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731-0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer-Lemeshow test: χ2 = 5.76, P = 0.451). The independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR > 1.33, non-R0 resection, and BMI < 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.

The Impact of BRAF Mutation Status on Survival Outcomes and Treatment Patterns among Metastatic Colorectal Cancer Patients in Alberta, Canada.

Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation status. The Alberta Cancer Registry was used to identify all patients >18 years old who had been diagnosed with mCRC in Alberta between 1 January 2017 and 31 December 2019 and had received at least one cycle of systemic therapy. Treatment patterns were compared between wild-type and mutant BRAF mCRC patients. Cox regression models and Kaplan-Meier curves were created to assess survival differences by both treatment pattern and BRAF status. A total of 488 patients were identified with mCRC, of which 42 (11.4%) were confirmed to have a BRAF mutation. The most common first-line treatment regimen was either capecitabine and oxaliplatin (CAPOX) or leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX). The median overall survival for mCRC patients was 20.01 months. Mutant BRAF patients had a median survival of 8.21 months compared to 20.03 months among those with wild-type BRAF. BRAF mutations among mCRC patients are associated with a considerably poor prognosis, reinforcing the need for clinical BRAF testing among newly diagnosed patients to better understand their prognosis.

Real-World Progression-Free Survival and Treatment Patterns for t(11;14) Positive Patients with Multiple Myeloma with at Least 2 Prior Lines of Treatment

Background : Multiple myeloma (MM) is a subclonal disease characterized by large heterogeneity with a complex treatment landscape. Patients with MM have a myriad of available treatment options, prescribed based on several factors, including genetic testing, comorbidities, risk status, age, patient preference, and/or prior treatment failures. Cytogenetic abnormalities determines risk stratification and prognosis. The prognostic significance of t(11;14)-positivity has been debated and it is currently considered a standard-risk abnormality; however, testing for t(11;14) may be of potential therapeutic significance. Despite recent advances in treatment that have improved response rates and survival, MM remains incurable. This results in a continuous treat-to-failure approach that eventually leads to a lack of effective therapeutic options. Treatment patterns and outcomes for patients by lines of therapy (LOT) in real-world settings provide important benchmarks for assessments of future targeted therapies. Methods : Data were retrospectively collected from the ConcertAI Patient360 database containing aggregated electronic health record data of patients treated in primarily community-based oncology centers in the US. Adults diagnosed with MM (2011-2022) who received a National Comprehensive Cancer Network-guideline recommended treatment and had ≥2-months follow up were included; this analysis focused on patients with relapsed or refractory (RR) MM who are t(11;14)-positive and received ≥2 prior lines of systemic therapy. Baseline characteristics were determined for the third-line plus (3L+) subgroup of patients with t(11;14) RRMM. Real-world progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results were stratified by the use of doublet or triplet regimens, in which patients were treated with 2 or 3 classes of treatments among 6 options (ie, proteasome inhibitors [PI], immunomodulatory imide drugs [IMID], anti-CD38 monoclonal antibodies, chemotherapy, BCL-2 inhibitors, exportin-1 inhibitors, or steroid therapy), respectively, at any time during the LOT. Results : Eighty-four patients with t(11;14) RRMM received 3L+ of therapy. Of patients, 43% were female, 20% were Black, and 75% were White. The median (range) age at diagnosis was 64 (37-84), and the median (range) follow-up since diagnosis was 76 (10-209) months. At 24 months since the initiation of treatment, the median (range) PFS for all t(11;14)-positive patients that received 3L+ of therapy was 7.5 (5.9-9.4) months, and the median (range) PFS rate was 14.8% (9.7%-22.5%) (Figure); the median (range) OS for all t(11;14)-positive patients that received 3L+ of therapy was 32.1 (25.4-48.0) months, and the median (range) OS rate was 58.3% (51.0%-66.6%). The most common treatment regimens used in 3L+ included Daratumumab + Pomalidomide ± Dexamethasone (12%), Venetoclax monotherapy (9%), Pomalidomide ± Dexamethasone (7%), and Bortezomib ± Dexamethasone (7%). Of doublet regimens used in 3L+ (n = 69 LOT), 18 (26%) were IMID + steroid, 14 (20%) were PI + steroid, and 11 (16%) monoclonal antibody (MA)+ steroid. For triplet regimens used at 3L+ (n = 97 LOT), 28 (29%) were IMID + MA + steroid, 23 (24%) were IMID + PI + steroid, and 12 (12%) were MA + PI + steroid. Triplet regimen use increased from 52% in 3L to 61% in 4L and was associated with slightly longer PFS in 3L, relative to doublet regimen use. For patients that received 3L+ therapies, the median (95% CI) PFS was 6.7 (5.4-11.1) months for patients receiving doublet regimens, and 7.7 (5.9-11.3) months for patients receiving triplet regimens. Conclusions: Triplet regimens were more commonly used than doublet regimens as 3L+ therapy. Triplets were also associated with slightly longer PFS in 3L; however, PFS rates were low and did not translate into longer OS, suggesting an unmet need for novel therapeutic options for patients with t(11;14) RRMM.

Real-World Treatment Patterns and Overall Survival Among Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients: A Retrospective Cohort Study Using Claims Data

Introduction: Acute myeloid leukemia (AML) is a malignant disorder of the bone marrow, characterized by abnormal clonal proliferation and differentiation arrest of myeloid progenitor cells. Prognosis is generally poor and worsens with age. While curative therapies are available, they are often unavailable to older patients and those with significant comorbidities due to high morbidity and mortality associated with intensive therapy. Since 2017, seven new systemic therapies have been approved for various AML patient populations, including those unfit for intensive therapy. This study aims to characterize first-line (1L) and second-line (2L) treatment patterns and outcomes in newly diagnosed (ND) and relapsed/refractory (R/R) AML patients, in the context of these newly available therapies. Methods: A large US administrative claims database (Optum) was used to identify ND AML patients between January 1, 2016, and August 31, 2022. The “ND index date” was defined as the first date a non-R/R AML diagnosis code was observed. To confirm that the initial AML diagnosis represented a true case of AML, ≥2 subsequent AML diagnoses within 60 days post-index were required. A washout period of 12 months was used to confirm no previous AML diagnosis. ND patients were required to have continuous enrollment from 1 year prior to the index until ≥30 days after the index date or death, whichever was earlier. A subgroup of R/R patients was then identified: all ND cohort members who 1) had an R/R AML diagnosis code, 2) had continuous enrollment between ND index date and ≥30 days after the RR index date, and 3) did not receive 1L hematopoietic stem cell transplant (HSCT) after the ND index date were eligible for inclusion. In this subgroup, the “RR index date” was defined as the first date an R/R AML diagnosis code was observed. Demographic characteristics, clinical characteristics, and treatment patterns over time were reported descriptively. Treatment regimens over time were described using the following classification: HSCT, intensive chemotherapy without targeted agents, intensive chemotherapy with targeted agents, hypomethylating agent (HMA) therapy only, other targeted therapy, Venetoclax-based therapy, unspecified/other treatment, no treatment/supportive care only. Overall survival (OS) was described using the Kaplan-Meier estimator. All analyses were stratified by line of therapy and transplant status. Results: We identified 5,135 ND AML patients and 934 R/R AML patients (ND cohort: mean age at initial AML diagnosis 73.5 years, mean follow-up time 6.1 months). ND patients receiving transplant in 1L tended to be younger and had fewer comorbidities than those not receiving transplant ( Table 1). Over the entire study period, 61% of ND patients and 69% of R/R patients received some treatment for AML; older patients were more likely to receive supportive care only. In 1L, Venetoclax-based and intensive chemotherapy without targeted agents were the most common treatment regimens (21% and 17% of all ND patients). In 2L, Venetoclax-based and HMA-only therapies were most common (17% and 16% of all R/R patients). Increases in the use of novel therapies (Venetoclax, intensive chemotherapy with targeted agents, or other targeted therapies) were observed in both 1L and 2L over the study period ( Figure 1). 1-year OS among ND patients was 32% in non-transplant recipients, and 84% in transplant recipients; among R/R patients, 1-year OS from RR index date was 21% in non-transplant recipients and 81% in transplant recipients. Conclusions: The findings from the present study indicate substantial disease burden and ongoing unmet need among ND and R/R AML patients in the USA. While treatment patterns for AML have changed significantly following the advent of novel therapies (with 41% of 1L patients and 31% of 2L patients being treated with novel therapies in 2022), OS remained low. Notably, around 1/3 of patients with RR AML did not receive active treatment; these patients tended to be older and were more frail. Increasing off-label use of Venetoclax in 2L further underscores high unmet need for patients who require more effective treatment options.

Real-World Treatment Patterns Following Update to National Comprehensive Cancer Network Guidelines for Light-Chain Amyloidosis: Results from a Us Administrative Claims Database

Background: Light-chain amyloidosis (AL) is a rare, multi-organ disease that can cause serious organ damage. In January 2021, a new therapy, daratumumab, was FDA-approved for the treatment of AL in combination with current standard-of-care (SoC) of bortezomib/cyclophosphamide/dexamethasone (CyBorD) and was classified as SoC according to the National Comprehensive Cancer Network (NCCN) guidelines. The objective of this study is to describe current real-world treatment patterns amongst patients with AL who newly initiated treatment January/2021 through June/2022. Methods: This study included patients aged ≥18 identified in the IQVIA PharMetrics database (&amp;gt;72 million lives 2021-2022 total) who were newly initiating pharmacological treatment with bendamustine, bortezomib, carfilzomib, cyclophosphamide, daratumumab, ixazomib, lenalidomide, melphalan, pomalidomide, or venetoclax 01Jan2021-30Jun2022 (date of first therapy classified as “index date”). Patients were required to have an ICD-10 diagnosis of AL (E85.81) identified during full study period (01Jan2020-30Sep2022) as well as continuous medical and prescription insurance enrollment from 1 year pre-treatment-index through 90-days post-treatment-index. Patients were excluded if they had any of the following: a claim indicating treatment with stem cell transplant; a diagnosis of familial mediterranean fever; a diagnosis of secondary, transthyretin, or hereditary amyloidosis; a diagnosis of a non-myeloma/non-lymphoma malignancy. Treatment patterns assessed included index treatment regimen and daratumumab adoption/use patterns at index, 30-days post-index, and 90-days post-index. Results: A total of 194 patients met all eligibility criteria, out of which the majority were male (N=119; 61%), with the largest insurance coverage being self-insured (N=80; 41%), and a mean age of 62 years (SD=9.8). The most common index treatment regimen was CyBorD+daratumumab (N=53; 27%) followed by dexamethasone+daratumumab (N=24;12%) and daratumumab monotherapy (N=16; 8%) ( Table). Across all treatment regimens at index date, daratumumab was found to be utilized by 62% (N=121) of patients. Furthermore, 76% (N=148) and 80% (N=155) of patients were found to have utilized daratumumab within 30-days or 90-days of treatment initiation, respectively. Discussion: AL is life threatening disease that impacts organ function and quality of life. Until 2021, there were no FDA approved therapies for AL. Daratumumab use was rapidly adopted to treat patients with AL following approval, in accordance with national guidelines, primarily in combination with other treatments such as CyBorD. This has changed the treatment paradigm providing hope to patients and clinicians to treat this devasting disease and should be informative for current and future clinical trial considerations in development of medications to treat AL.

Treatment options for neoadjuvant strategies of esophageal squamous cell carcinoma (Review).

Compared with postoperative adjuvant therapy, neoadjuvant therapy has more potential advantages, such as decreasing tumor stage, killing micrometastatic cells. Because of these advantages, neoadjuvant therapy is recommended for numerous types of tumor, such as breast, lung and rectal cancer. To determine the role of neoadjuvant therapy on overall survival and adverse for patients with resectable esophageal carcinoma. we summarized clinical studies on 7 types of neoadjuvant therapies in this review. Currently, patients with esophageal cancer (EC) in China mainly receive postoperative treatment with <30% of patients receiving neoadjuvant therapy. One reason for the limited use of neoadjuvant therapy in China is inaccurate staging based on imaging and neoadjuvant treatment may increase difficulties in surgery. After neoadjuvant therapy, there may be tissue edema, blurry surgical field of view and unclear tissue gaps, resulting in greater difficulty in surgical procedures. However, oncologists are interested in neoadjuvant treatment, especially neoadjuvant immunotherapy to treat EC. Concurrent chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) is the most common neoadjuvant treatment regimen and increases the pathological complete response (pCR) and 5- and 10-year survival rates. Preoperative induction chemotherapy and sequential concurrent chemoradiotherapy are currently the most widely treatments used in clinical practice in China. However, this treatment strategy does not yield long-term survival. The pCR rate of neoadjuvant immunotherapy is greater than that of concurrent chemoradiotherapy but, to the best of our knowledge, no evidence of long-term survival benefit has been found in phase I and II clinical trials. Neoadjuvant treatment should be considered for patients with locally advanced ESCC.

High incidence of antibiotic resistance amongst isolates of Helicobacter pylori collected in Nottingham, UK, between 2001 and 2018.

Introduction. Helicobacter pylori is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor (PPI) to suppress stomach acid. The World Health Organization designated clarithromycin-resistant H. pylori as a high priority pathogen for drug development, due to increasing antibiotic resistance globally.Hypothesis/Gap Statement. There is no routine surveillance of H. pylori primary antimicrobial sensitivities in the UK, and published data are lacking.Aim. This study aimed to characterize antimicrobial sensitivities of isolates collected in Nottingham, UK, between 2001 and 2018.Methodology. Gastric biopsy samples were collected, with informed written consent and ethics approval, from 162 patients attending the Queen's Medical Centre in Nottingham for an upper GI tract endoscopy. Antibiotic sensitivity was assessed using E-Tests and a more cost-effective disc diffusion test.Results. The clarithromycin, amoxicillin and levofloxacin disc diffusion tests provided identical results to E-Tests on a subset of 30 isolates. Disparities were observed in the metronidazole test results, however. In total, 241 isolates from 162 patients were tested using at least one method. Of all isolates, 28 % were resistant to clarithromycin, 62 % to metronidazole and 3 % to amoxicillin, which are used in first-line therapies. For those antibiotics used in second- and third-line therapies, 4 % were resistant to levofloxacin and none of the isolates were resistant to tetracycline. Resistance to more than one antibiotic was found in 27 % of isolates. The frequency of patients with a clarithromycin-resistant strain increased dramatically over time: from 16 % between 2001 and 2005 to 40 % between 2011 and 2018 (P=0.011). For the same time periods, there was also an increase in those with a metronidazole-resistant strain (from 58 to 78 %; P=0.05). The frequencies of clarithromycin and metronidazole resistance were higher in isolates from patients who had previously received eradication therapy, compared to those who had not (40 % versus 77 %, and 80 % versus 92 %, respectively). Of 79 pairs of isolates from the antrum and corpus regions of the same patient's stomach, only six had differences in their antimicrobial susceptibility profiles.Conclusion. Although there was high and increasing resistance to clarithromycin and metronidazole, there was no resistance to tetracycline and the frequencies of amoxicillin and levofloxacin resistance were very low.

Real-world treatment patterns, healthcare resource utilizationand costs among patients with peripheral T-cell lymphoma.

Objective: To evaluate treatment patterns, healthcare resource utilization (HRU)and costs among peripheral T-cell lymphoma (PTCL) patients in the USA. Methods: A retrospective cohort study, using theIQVIA PharMetrics® Plus claims database from 1April 2011 to 30November 2021, identified PTCL patients receiving systemic treatments. Three mutually exclusive subcohorts were created based on line of therapy (LOT): 1LOT, 2LOTand ≥3LOT. Common treatment regimens, median time on treatment, all-cause and PTCL-related HRU and costs were estimated. Results: Among 189 PTCL patients identified, 61.9% had 1LOT, 21.7% had 2LOTand 16.4% had ≥3LOT. The most common treatment regimens in the 1LOT were CHOP/CHOP-like, CHOEP/CHOEP-likeand brentuximab vedotin; monotherapies were most common in the 2LOT and ≥3LOT. All-cause and PTCL-related hospitalizations and prescriptions PPPM increased with increasing LOT. Nearly 70% of total treatment costs were PTCL related. Conclusion: Higher utilization of combination therapies in the 1LOT and monotherapies in subsequent LOTs were observed, alongside high PTCL-related costs.

Unmet clinical needs, burden of disease and treatment patterns in hidradenitis suppurativa: Real‐world experience from Spain

AbstractBackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. HS is difficult‐to‐treat, and a multifaceted treatment approach is recommended to achieve adequate clinical response. A greater understanding of HS treatment could help identify unmet clinical needs.ObjectivesTo evaluate disease characteristics and treatment patterns in a real‐world population of patients with HS in Spain.MethodsThis retrospective analysis utilised data collected from the Adelphi HS Disease Specific Programme between November 2020 and April 2021. Dermatologists completed patient record forms (PRFs) for consulting HS patients. Outcomes included disease severity, HS clinical signs, quality of life measures, medical treatments and previous surgeries.ResultsOverall, 53 dermatologists completed 332 PRFs, each representing one patient with HS. Based on physician‐judged disease severity at sampling, 73.8%, 22.9% and 3.3% of patients were classified as mild, moderate or severe, respectively. Overall, patients presented with 2.8±2.7 (mean±SD) HS symptoms, which increased with worsening disease severity. The most frequently reported symptoms were ‘inflammation/redness of HS lesions/abscess’ (45.9%), general pain/discomfort (39.9%) and pain on sitting (32.3%). Overall, patients reported a mean±SD Dermatology Life Quality Index score of 4.7±4.8, which increased with worsening disease severity (mild, 3.9±4.3; moderate, 8.7±5.1; moderate to severe, 9.0±5.1). When asked what effect HS had on everyday activities, a large proportion of patients reported that HS sometimes or greatly affected personal appearance/self‐confidence (66.0%), mood (60.2%), close personal relationships (60.4%), motivation (38.3%), leisure activities (43.0%) and feelings about the future (33.6%). At the time of HS diagnosis, the most frequently prescribed treatment regimens were topicals (70.7%), antibiotics (57.6%) and antiseptics (32.2%). At the time of sampling, the most common treatment regimens were biologics (43.8%), topicals (34.9%) and antibiotics (32.2%). The mean±SD number of surgical interventions was 0.6±0.8; incision and drainage (31.3%), local or limited excision (13.0%), and wide surgical excision of all hair‐bearing skin (9.9%) were the most common surgeries.ConclusionsThese real‐world data suggest a high disease burden in patients with HS in Spain. Patients received multiple treatments, and a notable proportion underwent surgery. More data are needed to define optimal HS management strategies.

Evaluation of Pathological Response Rate and Complications of FOLFOX versus FLOT Regimen in Perioperative Chemotherapy for Resectable Gastric Cancer: A Prospective Study.

Previous studies have shown that the perioperative and postoperative chemotherapy can lead to an improvement in the prognosis of patients with resectable gastric cancer (GC). There is no preference for postoperative chemotherapy with the two common treatment regimens, FLOT and FOLFOX, in these patients. The aim of this study was to compare FOLFOX and FLOT regimens in perioperative chemotherapy in resectable GC based on pathological response and complications. This prospective cohort study was conducted on 112 patients with resectable GC who were admitted to Firozgar Hospital affiliated with Iran University of Medical Sciences, Tehran, Iran between 2021 to 2022. Given the inclusion criteria, 80 patients were enrolled in the present study. Patients were divided into 2 groups based on the type of treatment regimen, FOLFOX (40 patients) and FLOT (40 patients). Tumor response was classified using Mandard Tumor regression grading system criteria into five categories of TRG1 to 5. Also, the side effects were classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. The rate of complete pathological response in FOLT group was significantly higher than FOLFOX group (35.0% vs 2.5%, p: 0.001). The frequency of neurological complications and hair loss in the FOLT group was significantly higher than the FOLFOX group (P<0.05). While no significant difference was observed in the frequency of hematological, Gastroenterological, hepatic, renal and stomatitis complications in the both groups (p>0.05). Our study showed that perioperative FLOT regimen has a better pathological response than FOLFOX regimen. The frequency of neurological complications and hair loss was significantly higher in patients treated with FLOT regimen. Thus, perioperative FLOT regimen may be recommended for treating GC patients.