First-line Chemoimmunotherapy Research Articles

First-line chemoimmunotherapy for patients with small-cell lung cancer and interstitial lung abnormality: CIP risk and prognostic analysis.

Patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor-related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small-cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first-line chemoimmunotherapy and to assess its relationship with prognosis. We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first-line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574-18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506-18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179-3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001-1.002; p < 0.001) were statistically significant for increased mortality risk in multivariate Cox regression analysis. In SCLC patients receiving first-line chemoimmunotherapy, baseline ILA is a risk factor for CIP and is associated with poorer prognosis.

P3.13D.05 Genomics and Immune Infiltration Biomarkers for Short-term and Long-Term ES-SCLC Survivors with First-Line Chemoimmunotherapy

P3.13D.05 Genomics and Immune Infiltration Biomarkers for Short-term and Long-Term ES-SCLC Survivors with First-Line Chemoimmunotherapy

A random survival forest-based pathomics signature classifies immunotherapy prognosis and profiles TIME and genomics in ES-SCLC patients

BackgroundSmall cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with high mortality, and only a limited subset of extensive-stage SCLC (ES-SCLC) patients demonstrate prolonged survival under chemoimmunotherapy, which warrants the exploration of reliable biomarkers. Herein, we built a machine learning-based model using pathomics features extracted from hematoxylin and eosin (H&E)-stained images to classify prognosis and explore its potential association with genomics and TIME.MethodsWe retrospectively recruited ES-SCLC patients receiving first-line chemoimmunotherapy at Nanjing Jinling Hospital between April 2020 and August 2023. Digital H&E-stained whole-slide images were acquired, and targeted next-generation sequencing, programmed death ligand-1 staining, and multiplex immunohistochemical staining for immune cells were performed on a subset of patients. A random survival forest (RSF) model encompassing clinical and pathomics features was established to predict overall survival. The function of putative genes was assessed via single-cell RNA sequencing.Results and conclusionDuring the median follow-up period of 12.12 months, 118 ES-SCLC patients receiving first-line immunotherapy were recruited. The RSF model utilizing three pathomics features and liver metastases, bone metastases, smoking status, and lactate dehydrogenase, could predict the survival of first-line chemoimmunotherapy in patients with ES-SCLC with favorable discrimination and calibration. Underlyingly, the higher RSF-Score potentially indicated more infiltration of CD8+ T cells in the stroma as well as a greater probability of MCL-1 amplification and EP300 mutation. At the single-cell level, MCL-1 was associated with TNFA-NFKB signaling and apoptosis-related processes. Hopefully, this noninvasive model could act as a biomarker for immunotherapy, potentially facilitating precision medicine in the management of ES-SCLC.

Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma.

Historically, the management of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) following first-line chemoimmunotherapy has been second-line chemotherapy, followed by high-dose chemotherapy and consolidative autologous hematopoietic stem cell transplantation (HSCT), resulting in durable remissions in approximately 40% of patients. In 2017, chimeric antigen receptor (CAR) T-cell therapy changed the landscape of treatment for patients with R/R DLBCL, with complete response rates ranging from 40-58% and long-term disease-free survival of >40% in the highest risk subgroups, including patients who relapsed after autologous HSCT. Since that time further studies have demonstrated improved overall response rates and survival outcomes in patients with primary refractory or early-relapsed (relapse within 1 year) DLBCL treated with CAR T-cell therapy compared with autologous HSCT, advancing CAR T-cell therapy into the second-line setting. However, >50% of patients will relapse in the post-CAR T-cell setting. In the past 2 years, two CD20 x CD3 bispecific antibodies were approved by the Food and Drug Administration for the treatment of R/R DLBCL after two or more lines of systemic therapy. These bispecific antibodies have demonstrated overall response rates exceeding 50% and durable remissions at >2 years of follow-up. Additionally, a notable treatment advantage of bispecific antibodies is their ability to be administered in the community setting, making treatment more accessible for patients. The development and advancement of these novel therapies raise questions regarding the ongoing role of HSCT in the management of R/R DLBCL and the best sequence of cellular and bispecific therapies to optimize patients' outcomes.

Using Deauville Scoring to Guide Consolidative Radiotherapy in Diffuse Large B-Cell Lymphoma

Background: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), to guide the utilization of consolidative RT, which may help spare low-risk DLBCL patients from unnecessary RT. Methods: We included all DLBCL patients diagnosed between 2010 and 2022 at the National Cancer Centre Singapore with DV measured at the end of the first-line chemoimmunotherapy. The outcome measure was time-to-progression (TTP). The predictive value of DV for RT was assessed based on the interaction effect between the receipt of RT and DV in Cox regression models. Results: The data of 349 patients were analyzed. The median follow-up time was 38.1 months (interquartile range 34.0–42.3 months). RT was associated with a significant improvement in TTP amongst the DV4-5 patients (HR 0.33; 95%CI 0.13–0.88; p = 0.027) but not the DV1-3 patients (HR 0.85; 95%CI 0.40–1.81; p = 0.671) (interaction’s p = 0.133). Multivariable analysis reported that RT was again significantly associated with improved TTP among the DV4-5 patients (adjusted HR 0.29; 95%CI 0.10–0.80; p = 0.017) but not the DV1-3 group (HR 0.86; 95%CI 0.40–1.86; p = 0.707) (interaction’s p = 0.087). Conclusion: Our results suggests that DLBCL patients with end-of-treatment PET-CT DV1-3 may not need consolidative RT. Longer follow-up and prospective randomized trials are still necessary to investigate long-term outcomes.

Complete Blood Count-Based Biomarkers as Predictors of Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients with PD-L1 < 50% Treated with First-Line Chemoimmunotherapy.

Background: The aim of the study was to investigate a series of complete blood cell count-based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC and PD-L1 < 50% who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78-10.82 vs. 3.31; IQR: 2.15-4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82-21.20 vs. 9.20; IQR: 7.45-11.20, p = 0.013), and systemic inflammation index (SII, median: 1395; IQR: 929-3334 vs. 945; IQR: 552-1373, p = 0.025), but only NLR and NMR remained independently associated with clinical response in multivariate logistic regression. In the univariate analysis, white blood cells (OR:1.2202; 95% CI: 1.0339-1.4400, p = 0.019), neutrophils (OR:1.2916; 95% CI: 1.0692-1.5604, p = 0.008), NLR (OR:1.3601: 95% CI: 1.0949-1.6896, p = 0.005) and NMR (OR:1.2159; 95% CI: 1.00396-1.4221, p = 0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR, and MLR were independently associated with survival; NLR, at a cut-off value of 4.0, showed the better AUC (0.749) in predicting OS. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

Comprehensive genomic and spatial immune infiltration analysis of survival outliers in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy

BackgroundA minority of patients with extensive-stage small cell lung cancer (ES-SCLC) exhibit prolonged survival following first-line chemoimmunotherapy, which warrants the use of reliable biomarkers. Here, we investigated the disparities in genomics and immune cell spatial distribution between long- and short-term survival of patients with ES-SCLC. MethodsWe retrospectively recruited 11 long-term (>2 years) and 13 short-term (<9 months) ES-SCLC survivors receiving first-line chemoimmunotherapy. The samples were processed using targeted next-generation sequencing (tNGS), programmed death ligand-1 staining, multiplex immunohistochemical staining for immune cells (mIHC), tumor mutation burden (TMB), and chromosomal instability score measurements. The expression of putative genes in SCLC at the bulk and single-cell RNA-sequencing levels, as well as the role of putative genes in pan-cancer immunotherapy cohorts, were analyzed. ResultsAt the genomic level, a greater proportion of the smoking signature and higher TMB (>3.1) were associated with favorable survival. At the single-gene and pathway levels, tNGS revealed that MCL1 and STMN1 amplification and alterations in the apoptosis pathway were more common in short-term survivors, whereas alterations in the DLL3, KMT2B, HGF, EPHA3, ADGRB3, lysine deprivation, and HGF-cMET pathways were observed more frequently in long-term survivors. mIHC analysis of immune cells with different spatial distributions revealed that long-term survivors presented increased numbers of M1-like macrophages in all locations and decreased numbers of CD8+ T cells in the tumor stroma. Bulk transcriptomic analysis demonstrated that high levels of STMN1 and DLL3 represented an immune-suppressive tumor immune microenvironment (TIME), whereas HGF indicated an immune-responsive TIME. The expression levels of our putative genes were comparative in both TP53/RB1 mutant-type and TP53/RB1 wild-type. At the single-cell level, STMN1, MCL1, and DLL3 were highly expressed among all molecular subtypes (SCLC-A, SCLC-N, and SCLC-P), with STMN1 being enriched in cell division and G2M checkpoint pathways. ConclusionsFor ES-SCLC patients receiving first-line chemoimmunotherapy, alterations in DLL3, KMT2B, HGF, EPHA3, and ADGRB3 and a greater proportion of M1-like macrophages infiltration in all locations were predictors of favorable survival, while MCL1 and STMN1 amplification, as well as a greater proportion of CD8+ T cells infiltrating the tumor stroma, predicted worse survival.

Identifying key circulating tumor DNA parameters for predicting clinical outcomes in metastatic non-squamous non-small cell lung cancer after first-line chemoimmunotherapy

Circulating tumor DNA (ctDNA) provides valuable tumor-related information without invasive biopsies, yet consensus is lacking on optimal parameters for predicting clinical outcomes. Utilizing longitudinal ctDNA data from the large phase 3 IMpower150 study (NCT02366143) of atezolizumab in combination with chemotherapy with or without bevacizumab in patients with stage IV non-squamous Non-Small Cell Lung Cancer (NSCLC), here we report that post-treatment ctDNA response correlates significantly with radiographic response. However, only modest concordance is identified, revealing that ctDNA response is likely not a surrogate for radiographic response; both provide distinct information. Various ctDNA metrics, especially early ctDNA nadirs, emerge as primary predictors for progression-free survival and overall survival, potentially better assessing long-term benefits for chemoimmunotherapy in NSCLC. Integrating radiographic and ctDNA assessments enhances prediction of survival outcomes. We also identify optimal cutoff values for risk stratification and key assessment timepoints, notably Weeks 6–9, for insights into clinical outcomes. Overall, our identified optimal ctDNA parameters can enhance the prediction of clinical outcomes, refine trial designs, and inform therapeutic decisions for first-line NSCLC patients.

Complex evaluation of serum immunoglobulin levels in patients with chronic lymphocytic leukemia: Significant increase in IgA after first-line chemoimmunotherapy.

The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) quantities in patients with chronic lymphocytic leukemia (CLL) has not been extensively studied. We analyzed Ig levels in 45 stable patients with indolent CLL (without indication for treatment) and 87 patients with progressive disease before first-line treatment. Fifty-five patients were evaluated again after the treatment with CIT. We observed significantly lower levels of all Ig classes and subclasses in patients with progressive disease compared to patients with indolent disease. After treatment, median IgA increased from 0.59 g/L to 0.74 g/L (p = 0.0031). In stable patients, lower IgA2 was associated with shorter time to first treatment, although it did not reach statistical significance (p = 0.056). Shorter overall survival was observed in patients with progressive disease and lower IgG2 (p = 0.043). Surprisingly, among the patients with progressive CLL, unmutated IGHV genes were associated with higher levels of IgG, IgG1 and IgM, while TP53 mutation and/or 17p deletion were associated with higher levels of IgA and IgA1. CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction.

Phase II study of nab-paclitaxel with gemcitabine for relapsed/refractory small cell lung cancer.

Patients with small cell lung cancer (SCLC) often respond to first-line chemoimmunotherapy. However, relapse is inevitable and is associated with a poor prognosis. Treatments for relapsed SCLC, such as lurbinectedin and topotecan, are limited by modest efficacy and significant hematologic adverse events, leaving a need for newer therapeutic agents or regimens. The combination of gemcitabine and nab-paclitaxel is active and safe in other types of malignancies, such as pancreatic cancer. We conducted a phase II trial evaluating the efficacy and safety of gemcitabine and nab-paclitaxel in patients with relapsed/refractory SCLC. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with confirmed complete or partial response. Secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety. Between October 2016 and May 2021, 32 patients were enrolled. Patients were followed for a median of 9.3 months (range 1.8-65.2). Median age was 65 years (range 48-81). Fifty percent of patients were female. Fifty-three percent of patients had platinum-resistant/refractory relapsed SCLC. The ORR was 28.1% (95% confidence interval [CI] 15.5-100%). Median PFS was 2.9 months (95% CI 2.4-3.6), and median OS was 9.3 months (95% CI 5.2-12.4). Seven patients (21.9%) developed grade 3 or 4 neutropenia. Our study showed that the combination of gemcitabine and nab-paclitaxel led to encouraging outcomes in relapsed/refractory SCLC. Further studies are needed to compare this combination with other treatments used for relapsed SCLC, including lurbinectedin, temozolomide, and topotecan. https://clinicaltrials.gov/study/NCT02769832?cond=NCT02769832&rank=1, identifier NCT02769832.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

The value of intervention with radiotherapy after first-line chemo-immunotherapy in locally advanced or metastatic esophageal squamous cell carcinoma: A multi-center retrospective study

BackgroundChemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0–8.3 months and progression-free survival (PFS, ∼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. MethodsPatients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. ResultsA total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1–34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0–15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. ConclusionOur multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.

Comparison of Efficacy and Safety of Combined Chemoimmunotherapy With or Without Radiation Therapy for Stage IVB Esophageal Squamous Cell Carcinoma: A Multicenter Propensity Score Matching Analysis

PurposeThis study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiotherapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). MethodsWe retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiotherapy of ≥ 40 Gy radiation dose to primary lesion, from four academic cancer centers between October 2018 and December 2022. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. ResultsIn the overall cohort of 409 patients, the group that received additional radiotherapy had superior overall survival (OS) (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.39-0.66, P < 0.001) and progression-free survival (PFS) (HR: 0.52, 95% CI: 0.40-0.66, P < 0.001) compared to the group that received chemoimmunotherapy alone. After 1:1 PSM, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiotherapy significantly improved OS and PFS (median OS: 24.9 vs. 14.6 months, P = 0.003; median PFS: 14.2 vs. 10.6 months, P = 0.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiotherapy was an independent prognostic factor for both OS (HR: 0.57, 95% CI: 0.41-0.81) and PFS (HR: 0.63, 95% CI: 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with non-regional lymph node metastases only who received radiotherapy (HR: 0.49, 95% CI: 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR: 0.72, 95% CI: 0.46-1.13). Regarding safety, the group receiving additional radiotherapy had higher incidences of grade 3-4 lymphopenia (74.4% vs. 17.7%, P < 0.001) and esophagitis (11.2% vs. 2.4%, P = 0.006). ConclusionThe addition of radiotherapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with non-regional lymph nodes metastasis.

The Evolving Role of Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.

The advent of targeted therapies such as monoclonal antibodies, adoptive T-cell therapies, and antibody-drug conjugates (ADCs) dramatically changed the treatment landscape of diffuse large B-cell lymphoma (DLBCL) over the last two decades. Rituximab was the first one approved. Chimeric antigen receptor T-cells are currently approved as second-line treatment in patients with DLBCL refractory to first-line chemo-immunotherapy. Polatuzumab, a CD79b-targeting ADC, is approved as first-line treatment in high-risk patients in combination with chemo-immunotherapy. Bispecific antibodies (BsAbs) are a novel category of drugs that are also changing the treatment paradigm of patients with DLBCL. They are engineered to bind to two different targets at the same time. To date, two BsAbs (glofitamab and epcoritamab) are approved as monotherapy in third-line treatment in DLBCL. Combination strategies with chemotherapy, immunotherapy, and ADCs are currently under investigation with encouraging results in first-line or subsequent lines of treatment. In the following review, we focus on the structure of BsAbs, the mechanism of action, clinical efficacy, and the mechanisms of resistance to BsAbs.

Development of a novel methodology to assess response to lymphoma treatment in real-world data.

e19081 Background: Innovation in the use of real-world data (RWD) for regulatory purposes is an important provision of 21st Century Cures Act. Numerous initiatives to enhance RWD methodologies in oncology drug development are ongoing, including evaluation of treatment response assessment to support effectiveness research. Blinded independent central review (BICR) standardizes response assessment in clinical trials, and corresponding RWD methodologies are needed. This study assess feasibility of BICR using RWD, and evaluates a novel, standardized treatment response methodology among patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective multisite chart review identified adult patients with DLBCL treated with first-line chemoimmunotherapy in US (01JAN2015-31DEC2022). Clinical data, including physician-reported response, were abstracted from medical charts and positron emission tomography-computed tomography (PET-CT) reports at treatment initiation and first response assessment. Lugano 2014 criteria, such as standardized uptake value (SUV) and Deauville score, were extracted and converted to an algorithm (rwLugano). Absence of normal tissue SUV in PET-CT reports was addressed using published values for background, mediastinum, and liver to facilitate a real-world Deauville (rwDeauville) score for rwLugano classification. PET-CTs underwent deidentified digital image transfer for BICR using Lugano 2014 criteria by two lymphoma radiologists. Descriptive analyses assessed BICR feasibility and completeness of rwLugano data elements. Results: Six oncology practices, comprising 77 physicians, abstracted medical records and PET-CT reports for 185 patients. PET-CT scans were available for BICR for 174/185 (94%) patients (41% female, mean age 66 years). BICR discordance for Deauville score at baseline and initial response occurred in 7% (12/174) and 29% (50/174), respectively. For response assessment per Lugano, BICR discordance occurred in 9% (16/174), and were further adjudicated by a third party. Lugano discordance was often related to interpretation of marrow activity and/or new disease sites, highlighting variability in lymphoma treatment response assessment. Medical record review found Deauville score charted for 97 (56%) patients at baseline and 145 (83%) at first response. Tumor SUV was complete (174/174, 100%) at baseline and for all patients (63/63, 100%) not charted as CR at first response. Thus, 29 patients (17%) required calculation of rwDeauville at first response, providing data to calculate rwLugano for all patients in the final cohort (174/174, 100%). Conclusions: This study suggests BICR, though resource intensive, can be performed, and the component measures necessary to assess response per Lugano criteria can be obtained using RWD. Accordingly, rwLugano warrants further analysis for concordance with BICR- and physician-reported response.

Clinical characteristic and survival outcomes of patients with advanced NSCLC according to KRAS mutational status in the French real-life ESME cohort

The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P= 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.

Prognostic value of body mass index for first-line chemoimmunotherapy combinations in advanced non-small cell lung cancer in Chinese population

BackgroundFew studies have examined the correlation between body mass index (BMI) and effectiveness of first-line chemoimmunotherapy in patients with advanced non-small cell lung cancer (NSCLC); moreover, the conclusion remains elusive and no such studies have been conducted in the Chinese population. Our study aimed to validate the predictive significance of BMI in Chinese patients with advanced NSCLC receiving first-line chemoimmunotherapy combinations. MethodsData of patients with advanced NSCLC treated with first-line chemoimmunotherapy between June 2018 and February 2022 at three centers were retrieved retrospectively. The association between baseline BMI with progression-free survival (PFS) and overall survival (OS) was evaluated using the Kaplan–Meier method and Cox regression models. BMI was categorized according to the World Health Organization criteria. ResultsOf the included 805 patients, 5.3 % were underweight, 63.4 % had normal weight, 27.8 % were overweight, and 3.5 % were obese. Survival analysis showed that patients in the high BMI group had significantly better PFS (p = 0.012) and OS (p = 0.014) than those in the low BMI group. Further, patients in the overweight subgroup had better PFS (p = 0.036) and OS (p = 0.043) compared to the normal weight population. The results of Cox regression analysis confirmed the correlations between BMI and prognosis of advanced NSCLC patients receiving first-line chemoimmunotherapy combinations. ConclusionsBaseline BMI affected the clinical outcomes of first-line chemoimmunotherapy combinations in patients with advanced NSCLC, and was especially favorable for the overweight subgroup.

Practical Application of Next-Generation Sequencing. Identification of STK11 and KEAP1 Mutations Determine Use of First-Line Chemoimmunotherapy

Practical Application of Next-Generation Sequencing. Identification of STK11 and KEAP1 Mutations Determine Use of First-Line Chemoimmunotherapy

Real-life clinical management patterns in extensive-stage small cell lung cancer across France: a multi-method study

BackgroundWe designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice.MethodsA 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers.ResultsIn ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2–7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI.ConclusionsThere is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting.

Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume

AbstractMetabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [median or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in patients who had a response). All P values are descriptive. Within high- and low-MTV subgroups, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care. EFS in patients with high MTV (vs low MTV) was numerically shorter with axi-cel and was significantly shorter with standard care. PFS was shorter in patients with high MTV vs low MTV in both the axi-cel and standard-care arms, and median MTV was lower in patients in ongoing response at data cutoff vs others. Median MTV was higher in patients treated with axi-cel who experienced grade ≥3 neurologic events or cytokine release syndrome (CRS) than in patients with grade 1/2 or no neurologic events or CRS, respectively. Baseline MTV less than or equal to median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.