Chemoimmunotherapy Group Research Articles

Adding immune checkpoint inhibitors to chemotherapy confers modest survival benefit in patients with small cell lung cancer and brain metastases: a retrospective analysis.

Brain metastases (BM) are highly prevalent and associated with a poor prognosis in patients with small cell lung cancer (SCLC). However, the evidence regarding the efficacy of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for patients with SCLC and BM remains limited. Therefore, the objective of this study is to evaluate whether the addition of ICIs confers survival benefits for patients with SCLC and BM. This retrospective study enrolled patients with SCLC and BM at the Sun Yat-sen University Cancer Center between January 2018 and December 2022. Clinical characteristics were extracted from medical records. Depending on whether ICIs were added to the first-line treatment, the patients were categorized into the chemotherapy group and the chemoimmunotherapy group. The efficacy of these two treatment approaches was analyzed and compared. A total of 165 patients were enrolled, with 85 in the chemotherapy group and 80 in the chemoimmunotherapy group. The chemoimmunotherapy group showed a tendency towards prolonged intracranial [6.6 vs. 5.9 months, hazard ratio (HR) =0.77; P=0.14] and extracranial (6.9 vs. 6.5 months, HR =0.73; P=0.12) progression-free survival (PFS) and overall survival (OS) (15.6 vs. 14.5 months, HR =0.98; P=0.93) compared to the chemotherapy group. Cox regression analysis identified liver metastases and local treatment for BM as independent prognostic factors for OS in patients. Furthermore, the chemotherapy group and the chemoimmunotherapy group demonstrated similar patterns of initial disease progression. Adding ICIs to chemotherapy confers modest survival benefits in patients with SCLC and BM.

Clinical outcomes and synergistic effect between radiotherapy and immunotherapy in patients with extensive-stage small cell lung cancer: a real-world study

BackgroundPatients with extensive-stage small cell lung cancer (ES-SCLC) experience significant therapeutic challenges and limited survival rates. This study aimed to investigate the efficacy of combining immunotherapy (IT) with chemotherapy (CT) for treating ES-SCLC and to explore the synergistic effect between radiotherapy (RT) and IT.MethodsThis retrospective analysis examined patients with ES-SCLC who received treatment at three centers. Furthermore, propensity score-matched (PSM) analysis was conducted. The Kaplan‒Meier method and Cox proportional hazards regression were used to compare the survival outcomes.ResultsA total of 257 eligible patients with ES-SCLC were included in the analysis. Among all patients, the median overall survival (mOS) was 18.0 m in the chemoimmunotherapy (CT + IT) group and 15.7 m in the CT group (p = 0.208). The median real-world progression-free survival (mrwPFS) was 7.7 m and 6.8 m (p = 0.043) in the CT + IT and CT group, respectively. Moreover, the mOS was 22.0 m in the chemoradiotherapy (CT + RT) group and 13.6 m in the CT group (p < 0.001). The mrwPFS was 7.4 m and 6.0 m (p = 0.175) in the CT + RT group and CT group, respectively. The multivariate analyses revealed that sex, liver metastasis and RT were independent prognostic factors for OS (p < 0.05), while liver metastasis and IT were found to be independent predictive factors of real-world progression-free survival (rwPFS) (p < 0.05). After PSM, the mOS was 23.2 m in the CT + IT group and 13.0 m in the CT group (p = 0.008). The mrwPFS was 7.3 m and 6.2 m (p = 0.096) in the CT + IT group and the CT group, respectively. Moreover, the mOS was 21.4 m in the CT + RT group and 12.5 m in the CT group (p < 0.001). The mrwPFS was 7.3 m and 5.2 m (p = 0.220) in the CT + RT group and the CT group, respectively. Additionally, our study revealed that in the PD-1 group, RT significantly improved patient survival (36.0 m vs. 15.8 m, p = 0.041).ConclusionAn increasing number of treatment options are being explored for ES-SCLC, and CT is the cornerstone of treatment for this disease. Combining CT with IT and RT has demonstrated remarkable efficacy and excellent safety profiles, and such treatments are worthy of further exploration.

The results of adding immunotherapy to chemotherapy in patients with small cell lung cancer: Registurk-Lung study—Real-world data.

e20006 Background: Evaluation of real-world data together with data in clinical studies is very important in the evaluation of treatment algorithms. In real life, treatments are applied to the elderly, patients with poor performance and unusual groups with comorbidities. Determining these treatment results is important in the creation of treatment algorithms. The studies on the addition of immunotherapeutic agents to the standard chemotherapy regimen in patients with small cell lung cancer have found a significant survival advantage. In this study, we evaluated the real-life reflections of the results of these clinical trials. Methods: In our country, within the scope of the Registurk-Lung observational study (NCT05254119), a total of 1008 patients with extensive stage small cell lung cancer were evaluated between December 2021 and December 2023 in 42 centers representing the whole country. The demographic, histopathological, molecular and clinical data of the patients were recorded. The relationship between progression-free survival (PFS) time and overall survival (OS) time with these characteristics was investigated. Results: The median age was 64 (31-88) years and 17.6% of the patients were female. The proportion of patients who never smoked was only 4.7 %. Histopathologically, 36.4% of the patients were diagnosed with squamous cell carcinoma. At the time of diagnosis, brain metastases were present in 13.9 % of the patients and liver metastases were present in 12.1% of the patients. Only 19.4 percent of patients received chemoimmunotherapy. Eighty-three percent of the patients received atezolizumab as immunotherapy in combination with chemotherapy and as maintenance treatment. The other patients received durvalumab and pembrolizumab.Patients who did not receive immunotherapy received platinum plus etoposide chemotherapy regimen as a medyan 4 cycle. The overall response rate was 49.0 % in the chemotherapy group and 52.8 % in the combination group. The PFS was 7.6 (95% CI: 6.9-8.3) months in chemoimmunotherapy group and 7.3 (95% CI: 6.5-8.1) months in chemotherapy group. Also, the OS was 15.5 months (95% CI: 11.1-19.9) in chemoimmunotherapy group and 11.8 (95% CI: 10.5-13.2) months in chemotherapy group. When the two groups were compared, there was a positive trend in terms of PFS in the immunochemotherapy group, but this difference was not statistically significant (p:0,802). In terms of overall survival, there was a statistically significant improvement in the chemoimmunotherapy group (p:0,049). Conclusions: The addition of immunotherapy to the treatment of patients with small cell lung cancer, which we have been treating with dual combination chemotherapy for many years, has provided a survival benefit. This situation brings with it new hopes for future studies.

Serial testing to assess cognitive function in patients with cancer being treated with immunotherapy.

TPS1644 Background: The advent of immunotherapy (IT) has revolutionized lung cancer treatment, becoming a primary modality from Stages Ib to IV. While the short-term side effects of IT are well documented, its long-term impact on cognitive function are under explored. This is a crucial area of investigation given the significant impact of cognitive health on the quality of life in cancer survivors. Preclinical investigations suggest neurocognitive alterations in IT-treated patients, evidenced by increased microglial activation and cytokine release, contributing to observed cognitive deficits such as impaired cued fear memory and object recognition. This study leverages the Montreal Cognitive Assessment (MoCA) to investigate these potential cognitive changes in a clinical setting, aiming to provide crucial insights into the long-term effects of IT. Methods: This single-center, open-label pilot study enrolls patients with various cancer types and stages undergoing IT. Exclusion criteria include prior history of underlying cognitive dysfunction, dementia, depression or psychiatric illness, history of brain metastasis or radiation. The study compromises three cohorts: those receiving IT alone, those undergoing chemo-immunotherapy, and a control group with no active treatment (in remission with prior history of cancer and have received IT in the past). Each of the IT and chemo-immunotherapy groups will include 72 patients, while the control group will consist of 40 participants. Baseline cognitive function is assessed using the MoCA scale, with follow-up assessments at 3 and 6 months from baseline. Patient enrollment commenced in April 2022, with 4 patients enrolled in the IT group, 16 in the chemo-IT group, and 32 in the control group. The primary objective is to assess the Cognitive function change in each individual group of patients. The secondary objective is to assess change of MoCA scores after 3 months and 6 months in patients receiving immunotherapy alone in lung cancer patients. The changes in MoCA scores will be plotted and summarized with mean change, standard deviation of change and standard errors of mean change. MoCA scores at baseline and at 6 months will be compared using paired t-tests. The study will analyze the rate of change in MoCA scores over time, comparing outcomes across the treatment cohorts. Clinical trial information: NCT06160700 .

The safety and efficacy of immune checkpoint inhibitor in combination with FOLFOX as neoadjuvant/adjuvant therapy in patients with locally advanced colon cancer.

e15621 Background: The recurrence rate of locally advanced colon cancer (T3-4 or N+, M0) after surgery is significantly high. Emerging data indicate that the combination of immunotherapy and chemotherapy demonstrates synergistic effects in other solid tumors. Consequently, a combination of immunotherapy and chemotherapy holds the potential to benefit patients with MSS and pMMR colon cancer. We have designed a prospective trial to investigate whether the immune checkpoint inhibitor (ICI) in combination with chemotherapy represents a safe and beneficial treatment approach for locally advanced colon cancer. Methods: Inclusive Criteria: Patients with locally advanced colon cancer (T3-4 or N+, M0) confirmed through pathological biopsy, with confirmed indications for neoadjuvant/adjuvant chemotherapy by the multidisciplinary team. Patients must be eligible for surgery, and a measurable mass must be identified according to RECIST version 1.1. All individuals aged over 18 years, with an estimated life expectancy of over one year and an ECOG score within 0-1, are eligible. The neoadjuvant chemoimmunotherapy group (NACI) includes mFOLFOX 6 (Q2W) and the anti-PD-1 monoclonal antibody (Toripalimab) (3mg/kg, Q2W), while the neoadjuvant chemotherapy group (NAC) receives only mFOLFOX 6 for neoadjuvant/adjuvant therapy (a total of 12 cycles, 6 cycles pre-surgery and 6 cycles post-surgery). The primary endpoint is the pathological complete response (pCR) rate. Results: From 2019 to 2022, a total of 22 patients were enrolled in the study, with 13 in the NACI group and 9 in the NAC group. The research findings indicate that in the NACI group, over 30% (4/13) of patients achieved a pathological complete response (pCR), whereas none of the patients in the NAC group reached pCR (0/9). Among the pCR patients, one was identified as MSI-H/dMMR, two as MSS/pMMR, and one had an unknown status. Tumor regression grade (TRG) levels also revealed that all patients in the NACI group were below grade 2, significantly outperforming the NAC group (P &lt; 0.05), with statistically significant differences. However, no significant differences were observed between the NAC and NACI groups in terms of CT regression percentage, R0 resection, vascular cancer emboli, and the level of neural invasion. Adverse reactions did not show significant differences between the two groups. Conclusions: The combination of immunotherapy and chemotherapy exhibits a synergistic effect in treating locally advanced colorectal cancer. Tolerable adverse reactions suggest that neoadjuvant chemoimmunotherapy could potentially serve as a novel therapeutic option. Clinical trial information: NCT03985891 .

Institutional Experience With Robotic Lobectomy After Neoadjuvant Immunotherapy and Chemotherapy

BackgroundThe real-world safety of robotic resections after neoadjuvant chemoimmunotherapy remains poorly defined in patients with non-small cell lung cancer. Due to reported increased operative challenges after neoadjuvant immunotherapy, we aim to describe our early institutional experience and outcomes after robotic resection in this clinical context. MethodsWe performed a retrospective chart review of patients with non-small cell lung cancer who underwent a robotic lobectomy, comparing patients from June 1, 2022, through October 31, 2023, who were treated with neoadjuvant chemoimmunotherapy consistent with the Checkmate-816 protocol and a control group with upfront resection. ResultsA total of 21 patients underwent neoadjuvant chemoimmunotherapy and robotic lobectomy in our cohort, and 64 patients were in the control group. Compared with control, the median tumor size was 3.2 cm vs 2.0 cm (P = .001). The most common clinical stage was IIIA (11 patients, 52%) in the neoadjuvant chemoimmunotherapy group and IA2 in the control group (26 patients, 45%) (P < .001). Operative time was greater in the neoadjuvant chemoimmunotherapy group (224 vs 177 minutes, P = .011). The median quantity of lymph nodes resected in the neoadjuvant chemoimmunotherapy group was greater (21 vs 16.5, P = .042). A R0 resection was achieved in all cases and no conversions to an open lobectomy occurred. Postoperative length of stay was 2 days in both groups (P = .92), and there were similar rates of postoperative air leak (33% vs 48%, P = .23) and acute post-hemorrhagic anemia (19% vs 14%, P = .58). ConclusionsIn our cohort, robotic-assisted lobectomy was safe and of comparable quality in the setting of neoadjuvant chemoimmunotherapy.

Comparison of neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable stage III non-small cell lung cancer: a real-world cohort study.

We compared the real-world efficacy and safety of neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with stage III non-small-cell lung cancer (NSCLC). A total of 59 consecutive patients were finally selected and divided into two groups: the neoadjuvant chemotherapy group (n = 33) and the neoadjuvant chemoimmunotherapy group (n = 26). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, and adverse events. All patients were followed up to collect perioperative pathology and clinical data. The objective response rate (ORR), pathological complete response (pCR), and major pathological response (MPR) were significantly higher in the neoadjuvant chemoimmunotherapy group than in the neoadjuvant chemotherapy group (73.1% vs. 45.5%, 34.6% vs. 3.0%, and 65.3% vs. 15.1%, respectively; P < 0.05). There was no statistically significant difference in disease-free survival between the neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy groups (P = 0.129). Patients in the neoadjuvant chemoimmunotherapy group had a higher rate of tumor regression than those in neoadjuvant chemotherapy group (37.0% [25 patients] vs. 29.0% [33 patients], P = 0.018). However, no discernible correlation between MPR achievement and the degree of tumor shrinkage was observed in either group (P > 0.05). The cumulative MPR rates were 42.3, 50, and 65.3% for 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemoimmunotherapy group and 9.1, 12.1, and 15.1% for ≤ 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemotherapy group. Moreover, No statistical difference was observed between the two groups regarding postoperative complications, resection range, operation time, surgical method, and extent of resection (P > 0.05). Although the incidence of grades III-IV adverse events was higher in the neoadjuvant chemotherapy group than in the neoadjuvant chemoimmunotherapy group (33.3% vs. 4.6%, P = 0.042), there was no significant difference in the incidence of adverse events between the two groups (64.6% vs. 83.6%, P = 0.072). In stage III NSCLC, neoadjuvant chemoimmunotherapy achieved higher pathological and clinical remission rates than chemotherapy alone, with compromising safety, making it an attractive choice for neoadjuvant therapy.

Treatment patterns and clinical outcomes in 157 patients with extensive-stage small cell lung cancer: real-world evidence from a single-center retrospective study.

Immune checkpoint inhibitors (ICIs) have changed the therapeutic options for extensive-stage small-cell lung cancer (ES-SCLC). In this real-world study, we analyzed the treatment patterns in patients with ES-SCLC and evaluated the efficacy of chemotherapy combined with immunotherapy as first-line therapy. A retrospective analysis was performed on patients with ES-SCLC who received treatment at China-Japan Friendship Hospital (Beijing, China) between August 1, 2020, and April 30, 2023. The treatment patterns appeared in the form of Sunburst Chart and Sankey diagram. The survival analyses were conducted by Kaplan-Meier curves. A total of 157 patients with ES-SCLC were retrospectively included. According to first-line therapy, patients were divided into the chemotherapy (CT) group (n=82) and chemo-immunotherapy (CIT) group (n=75). The median treatment lines were 2[1, 2] and cycles were 8[5, 12], respectively. 82 patients received the second line of therapy, followed by 37 for the third, 15 for the fourth, 11 for the fifth, and 5 for the sixth. Overall, the treatment patterns involved 11 options including 12 chemotherapy regimens, 11 ICIs, and 4 targeted agents. The second-line treatment pattern had the most options (9) and regimens (43). In the first 3 lines, chemotherapy was the largest proportion of treatment options. The addition of ICIs prolonged progression-free survival from 6.77 (95% confidence interval [CI], 6.00-7.87) to 7.33 (95% CI, 6.03-9.80) months (hazard ratio [HR]=0.67, 95% CI, 0.47-0.95; P=0.025), overall survival from 12.97 (10.90-23.3) to 14.33 (12.67-NA) months without statistically significant difference (HR=0.86, 95% CI, 0.55-1.34; P=0.505). The treatment options of patients with ES-SCLC are more diversified. Combination therapy is the current trend, where chemotherapy is the cornerstone. Meanwhile, ICIs participate in almost all lines of treatment. However, the clinical efficacy remains barely satisfactory. We are urgently expecting more breakthrough therapies except immunology will be applied in the clinic.

Treatment Selection and Clinical Outcomes in Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia (LPL/WM) - a Single Center Analysis

Introduction: Lymphoplasmacytic lymphoma (LPL) is as an indolent neoplasm of B-lymphocytes with plasmacytic differentiation causing bone marrow infiltration along with variable involvement of lymph nodes/or spleen. Most common subtype of LPL, Waldenstrom Macroglobulinemia (WM) involves IgM monoclonal gammopathy of any concentration. Due to widespread availability of targeted therapy drugs (BTKi), the treatment landscape of LPL is changing. The aim of this study is to analyze disease characteristics, patterns of real-world treatment selection and its impact on clinical outcomes (Objective response rate (ORR), Progression free survival (PFS) and Overall survival (OS). Methods: A retrospective analysis of patients (age ≥18 years) with diagnosis of LPL/WM between January 1, 2003, to March 31, 2023, seen in consultation at Roswell Park Comprehensive Cancer Center was performed. ORR (CR, VGPR, PR and MR) was calculated according to response criteria at 6 th International Workshop for WM. Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). OS and PFS were reported using standard Kaplan-Meier methods. Multivariate cox regression modeling was used to assess associations between first line regimen and survival outcomes (OS / PFS). Predictor variables, namely age at diagnosis, gender, Charlson Comorbidity Index (CCI) score, and rIPSS (revised International Prognostic Score System) were included in multivariable models. Results: A total of 127 patients were included in this study. The median age at diagnosis was 68 years (range 41 to 88), of which 75 (59.1%) were men. Majority of the population was White (n=112, 88.2%) and had ECOG of 0 (n=70, 67.3%). Monoclonal gammopathy of IgM subtype was present in 114 (94.2%), IgG in 3 (2.5%) and IgA in 1 (0.8%) patient. MYD88 mutation testing was positive in 69.8%, negative in 14% and unknown in 16.3% patients. Two out of 10 patients tested for CXCR4 mutation were positive. Sixteen (28.1%) patients had hyperviscosity symptoms and underwent plasmapheresis with first line treatment. These patients had a mean IgM level of 6249.5 mg/dL and mean M-spike of 4.53 g/dL. Of 121 patients with data on treatment strategy, 20 (16.5%) were monitored with observation alone. The most common treatment modality used in first line was chemo-immunotherapy (C-I) in 61 (50.4%) patients followed by Rituximab immunotherapy (R-I) in 20 (16.5%) patients and BTK inhibitors in 12 (9.9%) patients. ORR was highest 90.7% (39/43) in chemoimmunotherapy group, 87.5% (7/8) in BTKi group and 71.4% (10/14) in Immunotherapy group. Bendamustine-Rituximab was the most common used treatment regimen (n=42), with resultant CR in 20% and VGPR in 23.3% patients. At median follow-up duration of 36.9 months, median OS was 113.9 months in R-I, 159.8 months in C-I and not reached (NR) in BTKi group. The median PFS was 50.2 months in R-I, 61.2 in C-I and 23 months in BTKi group. Although Multivariate Cox Regression analysis failed to show statistically significant difference in PFS, there is tendency towards improved OS in C-I group (p=0.08) among all the groups when adjusted for age, sex, CCI. Conclusion: In our single center experience, chemoimmunotherapy combination with Bendamustine-Rituximab is the most used treatment choice in first line settings followed by single agent anti-CD20 therapy and BTKi. Although Multivariate Cox Regression analysis failed to show statistically significant difference in PFS, there is a tendency towards improved OS in the chemoimmunotherapy subgroup (p=0.08). The shorter PFS in BTKi group is likely due to toxicity of targeted therapy leading to treatment interruption and change of therapy.

Effectiveness of Chemo-Immunotherapy (CIT) and Novel Therapies in Second or Later Line of Therapy (2L+) for Patients with Relapsed/Refractory (R/R) Aggressive Large B-Cell Lymphoma (LBCL)

Aim: Patients with R/R LBCL after first-line treatment have poor prognosis. Multiple novel therapies have been approved for R/R LBCL in recent years, but CIT regimens are still commonly used. This study evaluated the effectiveness of CIT and novel therapies in 2L+ in patients with R/R LBCL and the association between patient clinical characteristics and real-world outcomes. Methods: This was a multi-site retrospective observational study of patients aged ≥18 years with R/R LBCL in the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (patients followed from 1/1/2015 to 2/15/2023) who were treated with CIT or novel therapy in 2L+. CIT regimens included salvage/palliative chemotherapy, lenalidomide, rituximab, or obinutuzumab, used alone or in combination. Novel therapies included polatuzumab vedotin plus bendamustine and rituximab or variations thereof (i.e., pola-based regimen), tafasitamab plus lenalidomide or variations thereof (tafa-based regimen), and loncastuximab tesirine (lonca). Patients' demographic and clinical characteristics were assessed from the first confirmed R/R disease diagnosis and initiation of 2L+ therapy. When multiple lines of therapy (LOTs) were eligible for inclusion in the analysis, one was randomly selected as the index LOT. Real-world outcomes, determined by investigators at each clinical site, including overall response rate (ORR), complete response (CR) rate, duration of response (DOR), duration of complete response (DOCR), progression-free survival (PFS), and overall survival (OS) were described for all patients in each treatment group and for the subgroup of patients with prior chimeric antigen receptor (CAR) T-cell therapy. Multivariable Cox Proportional Hazards models were used to assess associations between select patient clinical characteristics and real-world outcomes. Results: The study population included patients treated with CIT (N=653), pola-based regimen (N=116), tafa-based regimen (N=55), and lonca (N=42) ( Figure 1A). The median (m) age at date of index treatment initiation across groups ranged from 63 to 74 years. Across groups, most patients had primary refractory disease-i.e., were refractory to the first LOT (69.5% CIT vs. 73.3% pola vs. 58.2% tafa vs. 71.4% lonca), whereas variable proportions had one prior LOT (65.5% vs. 17.2% vs. 43.6% vs. 7.1%) and prior CAR T-cell therapy (5.1% vs. 43.1% vs. 32.7% vs. 47.6%). In the CIT group, ORR was 33.8%, 15.5% of patients achieved CR, mPFS (95% CI) was 1.9 (1.7, 2.1) months, and mOS was 9.1 (8.1, 10.5) months. In the pola group, ORR was 42.2%, 24.1% of patients achieved CR, mPFS was 2.5 (2, 3.2) months and mOS was 7.8 (6.4, 11.8) months. In the tafa group, ORR was 25.5%, 14.5% of patients achieved CR, mPFS was 2.7 (2.1, 4.2) months, and mOS was 8 (5.3, 12.7) months. In the lonca group, ORR was 40.5%, 21.4% of patients achieved CR, mPFS was 3 (2.1, 5.1) months, and mOS was 4.7 (3.7, 10.8) months. Demographics and outcomes for all patients and those who received prior CAR T-cell therapy are summarized in Figure 1A. In the multivariable Cox regression analysis, International Prognostic Index (IPI) risk score ≥3, CIT as the index treatment type, and primary refractory status were significantly associated with time from response to progression/death (P&amp;lt;0.05; Figure 1B). IPI risk score ≥3, CIT as the index treatment type, and primary refractory status were significantly associated with worse PFS. IPI risk ≥3, ≥3 prior LOTs, and primary refractory status were significantly associated with OS. Conclusion: In this large clinical cohort of patients with R/R LBCL with high proportions having primary refractory disease, all common treatments were associated with modest ORR/CR and poor OS. Receiving CIT treatments, higher IPI score, primary refractory status, and higher number of prior LOTs were significantly associated with poor clinical outcomes. A study with larger sample size and longer follow-up may be warranted to further understand the clinical effectiveness of novel treatments. Thus, despite the availability of novel treatments during the study period, these findings highlight the need for more effective treatment alternatives beyond currently available options to improve outcomes.

Use of Prephase Steroids in Older Patients Treated for Diffuse Large B-Cell Lymphoma

Background Treatment related morbidity and mortality (TRM) are significant contributors to overall morbidity and mortality for elderly patients with diffuse large B-cell lymphoma (DLBCL). Several studies have shown that TRM is greatest during the first two cycles of treatment. While attenuated doses of standard-of-care treatment regimens (such as R-mini-CHOP) are commonly used to reduce TRM, one additional strategy that has shown promise is the use of glucocorticoids prior to initiation of systemic chemoimmunotherapy (CIT). This approach, defined as prephase steroid use, has been evaluated in small studies, primarily single-center and retrospective in nature. However, older patients with comorbidities are both at greatest risk of TRM and less frequently included in clinical trials. Moreover, patient populations may differ across clinical settings. We conducted an analysis of prephase steroid use in a broader, real-world population treated across multiple centers. Methods We used longitudinal data from the US nationwide, Flatiron Health electronic health record-derived de-identified database. We included patients aged &amp;gt;60 with a diagnosis of DLBCL treated with CIT. This included high-grade B-cell lymphoma, but omitted diagnoses of Burkitt's or primary CNS lymphoma. We utilized a prespecified data analysis plan to determine whether outcomes differed by our exposure of interest, use of prephase steroids. The primary outcome measure was the combined endpoint of time to start of next treatment or death (real-world time to next treatment [rwTTNT]). The secondary outcome was real-world overall survival (rwOS). Outcomes were measured from frontline treatment start date. We also assessed rates of dose delays to evaluate whether prephase steroid use facilitates the maintenance of dose intensity. Prephase steroid use (the exposure) was defined as an order or administration for steroids occurring 5-21 days prior to the start of antineoplastic therapy (excluding steroids used as part of a standard treatment regimen). Patients were stratified by use of anthracycline-based CIT, with sensitivity analyses conducted limited to the anthracycline CIT group. To reduce confounding, we used propensity score-based inverse probability of treatment weighting (IPTW) for the primary analysis. Time to event endpoints were assessed using weighted Kaplan-Meier curves and log-rank tests. Odds of dose delays were assessed using weighted logistic regression. Results We included 3587 patients meeting our criteria, of whom 569 (15.9%) received prephase steroids prior to first-line CIT. A greater percentage of patients treated with anthracycline-based CIT received prephase steroids as compared to those treated with non-anthracyline CIT: 16.3% vs 12.4%, respectively (Table 1). In adjusted analysis using IPTW, there was no significant difference in the rwTTNT by prephase steroid use (p=0.807, Figure 1). Median rwTTNT was 41.2 months (95% CI, 34.6 to 52.4) vs 40.8 months (95% CI, 35.1 to 46.7) with and without prephase steroids, respectively. There was no difference in median rwOS by prephase steroid use: 65.7 months (95% CI, 52.4 to 84.8) vs 74.8 months (95% CI, 67.4 to 82.5) (p=0.707). No differences were seen in sensitivity analyses limiting to patients treated with anthracycline-based CIT. For dose delays, adjusted analysis showed a numerically lower odds of dose delay in patients administered prephase steroids in the total study population: 40.6% vs 50.7% (OR 0.796; p=0.0569). Discussion In this retrospective study of 3587 real-world, elderly patients with DLBCL, prephase steroid use within 21 days of induction CIT did not improve the rwTTNT or rwOS. There was a suggestion that use of prephase steroids may promote maintenance of dose intensity by reducing delays in CIT administration, though this finding did not reach statistical significance. The strengths of this analysis included use of a large, nationwide, real-world dataset and propensity score methods to control for confounding. Limitations include the retrospective nature of the study and potential for unmeasured confounding. In summary, in a real-world cohort of older patients with DLBCL, use of prephase steroids was not associated either with longer TTNT/death, or with longer OS. However, it may be associated with maintenance of CIT dose intensity. This finding is worth exploring in future studies.

First-Line Chemoimmunotherapy versus Sequential Platinum-Based Chemotherapy Followed by Immunotherapy in Patients with Non-Small Cell Lung Cancer with ≤49% Programmed Death-Ligand 1 Expression: A Real-World Multicenter Retrospective Study.

The long overall survival (OS) observed among patients with non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression in chemoimmunotherapy (CIT) groups in previous phase III trials suggests the limited efficacy of CIT among the subgroup with ≤49% PD-L1 expression on tumor cells. Hence, sequential treatment with first-line platinum-based chemotherapy followed by second-line immune checkpoint inhibitor treatment (SEQ) is an option. This study examined whether first-line CIT would provide better outcomes than SEQ in patients with advanced NSCLC with ≤49% PD-L1 expression. This retrospective study evaluated patients with untreated NSCLC who received first-line CIT or SEQ at nine hospitals in Japan. OS, progression-free survival (PFS), PFS-2 (the time from first-line treatment to progression to second-line treatment or death), and other related outcomes were evaluated between the CIT and SEQ groups. Among the 305 enrolled patients, 234 eligible patients were analyzed: 165 in the CIT group and 69 in the SEQ group. The COX proportional hazards model suggested a significant interaction between PD-L1 expression and OS (p = 0.006). OS in the CIT group was significantly longer than that in the SEQ group in the 1-49% PD-L1 expression subgroup but not in the <1% PD-L1 expression subgroup. Among the subgroup with 1-49% PD-L1 expression, the CIT group exhibited longer median PFS than the SEQ group (CIT: 9.3 months (95% CI: 6.7-14.8) vs. SEQ:5.5 months (95% CI: 4.5-6.1); p < 0.001), while the median PFS in the CIT group was not statistically longer than the median PFS-2 in the SEQ group (p = 0.586). There was no significant difference between the median PFS in the CIT and SEQ groups among the <1% PD-L1 expression subgroup (p = 0.883); the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group (10.5 months (95% CI: 5.9-15.3) vs. 6.4 months (95% CI: 4.9-7.5); p = 0.024). CIT is recommended for patients with NSCLC with 1-49% PD-L1 expression because it significantly improved OS and PFS compared to SEQ. CIT had limited benefits in patients with <1% PD-L1 expression, and the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group. These findings will help physicians select the most suitable treatment option for patients with NSCLC, considering PD-L1 expressions.

RBM17 Expression Is Associated With the Efficacy of ICI Monotherapy in NSCLC With Low PD-L1 Expression.

Immune checkpoint inhibitors (ICIs) are currently a standard treatment tool for non-small cell lung cancer (NSCLC). RNA-binding motif protein 17 (RBM17), a splicing factor, is frequently over-expressed in NSCLC, but little is known about the role of RBM17 in the efficacy of ICIs for NSCLC. Thus, we investigated the correlation between RBM17 expression and ICI efficacy in NSCLC. Biopsy or surgical specimens were collected from patients with advanced or recurrent NSCLC who received ICI monotherapy or chemo-immunotherapy in a first-line setting. RBM17 expression was examined using immunohistochemistry. The correlation between the efficacy of ICI monotherapy or chemo-immunotherapy and RBM17 expression was evaluated. Among the 218 cases, 115 (52.8%) cases were positive for RBM17 expression. RBM17 expression was not associated with the objective response rate (ORR) or progression-free survival (PFS) in either of the ICI monotherapy or chemo-immunotherapy groups. However, among those with a low PD-L1 expression level (PD-L1 <50%; n=86), RBM17 expression was significantly associated with a better ORR (p=0.045) and a better PFS (p<0.001) in the ICI monotherapy group, and was significantly associated with a poor ORR in the chemo-immunotherapy group (p=0.041). RBM17 might be a useful predictive marker for a higher efficacy of ICI monotherapy in NSCLC patients with a low PD-L1 expression level.

Assessing treatment outcomes of chemoimmunotherapy in extensive-stage small cell lung cancer: an integrated clinical and radiomics approach

BackgroundSmall cell lung cancer (SCLC) is a highly malignant cancer characterized by metastasis and an extremely poor prognosis. Although combined chemoimmunotherapy improves the prognosis of extensive-stage (ES)-SCLC, the survival benefits...

First-line immunotherapy combinations for recurrent or metastatic nasopharyngeal carcinoma: An updated network meta-analysis and cost-effectiveness analysis.

Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. RCTs estimating immunotherapies for R/M-NPC were searched. A Bayesian network meta-analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS). The cost and efficacy of four first-line therapies were evaluated using the Markov model. The main outcome in the cost-effectiveness analysis (CEA) was incremental cost-utility ratios (ICURs). The model robustness was assessed by one-way, three-way, and probabilistic sensitivity analyses. Three RCTs (JUPITER-02, CAPTAIN-1st, and RATIONALE-309) involving 815 patients were included in the NMA. Compared with PLGP, chemo-immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost-effective option among chemo-immunotherapy groups. From the Chinese payers' perspective, first-line immunotherapy combination therapies provided significant survival and cost-effectiveness superiority over chemotherapy alone for patients with R/M-NPC at the WTP of $38 029/QALY. Among the three chemo-immunotherapy groups, TOGP was the most cost-effective option.

Chemoimmunotherapy as the First-Line Treatment for Patients With Extensive-Stage Small-Cell Lung Cancer and an ECOG Performance Status 2 or 3

BackgroundStudies demonstrated that chemoimmunotherapy prolongs progression-free survival (PFS) and overall survival (OS) in patients with extensive-stage small-cell lung cancer (ES-SCLC) and an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. However, there is little data regarding chemoimmunotherapy in patients with ES-SCLC and an ECOG PS 2 or 3. This study aims to evaluate the benefits of chemoimmunotherapy compared to chemotherapy in the first-line treatment of patients with ES-SCLC and ECOG PS 2 or 3. Materials and MethodsThis retrospective study analyzed 46 adults treated at Mayo Clinic between 2017 and 2020 with de novo ES-SCLC and an ECOG PS 2 or 3. Twenty patients received platinum-etoposide and 26 patients received platinum-etoposide and atezolizumab. Progression-free survival (PFS) and Overall survival (OS) were calculated using Kaplan-Meier methods. ResultsPFS was longer in the chemoimmunotherapy group compared to the chemotherapy group, 4.1 months (95% confidence interval [CI]: 3.8-6.9) vs. 3.2 months (95% CI: 0.6-4.8), respectively; P = 0.0491. However, there was no statistically significant difference in the OS between the chemoimmunotherapy and chemotherapy group, 9.3 months (95% CI: : 4.9-12.8) vs. 7.6 months (95% CI: 0.6-11.9), respectively; P = .21. ConclusionChemoimmunotherapy prolongs PFS compared to chemotherapy in patients with newly diagnosed ES-SCLC and an ECOG PS 2 or 3. No OS difference was observed among the chemoimmunotherapy and chemotherapy groups; nevertheless, this may be attributed due to the small sample size of the study.

First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia

BackgroundRandomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking.MethodsIn a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine–cyclophosphamide–rituximab or bendamustine–rituximab) or 12 cycles of venetoclax–rituximab, venetoclax–obinutuzumab, or venetoclax–obinutuzumab–ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10−4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival.ResultsA total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax–rituximab, 229 to venetoclax–obinutuzumab, and 231 to venetoclax–obinutuzumab–ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax–obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax–obinutuzumab–ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax–rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P=0.32). Three-year progression-free survival was 90.5% in the venetoclax–obinutuzumab–ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax–obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax–rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P=0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax–obinutuzumab–ibrutinib (21.2%) than with venetoclax–rituximab (10.5%) or venetoclax–obinutuzumab (13.2%).ConclusionsVenetoclax–obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA–CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.)

Real-world experience of postoperative adjuvant chemoimmunotherapy in patients with perihilar cholangiocarcinoma at high risk of recurrence.

This study aimed to assess whether postoperative adjuvant chemoimmunotherapy could lead to better clinical outcomes for high-risk patients with perihilar cholangiocarcinoma (pCCA). In the cohort study, we retrospectively reviewed patients who received surgical resection for pCCA with curativeintent from January 2018 to December 2021 at the Sun Yat-sen Memorial Hospital. The patients athighriskforrelapse were further analyzed. Among them, 20 patients received adjuvant chemoimmunotherapy, 28 patients received adjuvant chemotherapy, and 33 patients received surgery alone. The oncological outcomes and drug-associated adverse events were evaluated. The 2-year overall survival (OS) rates in patients treated with adjuvant chemoimmunotherapy, adjuvant chemotherapy, and surgery alone were 80.0%, 49.4% and 22.6%, respectively. Univariable and multivariable Cox analyses showed that the treatment regimen and TNM stage were associated with adverse OS. Adjuvant chemoimmunotherapy led to an increase in OS compared with adjuvant chemotherapy [hazard ratio (HR) = 3.253; 95% confidence interval (CI) 1.072-9.870; P = 0.037] or surgery alone (HR = 7.560; 95% CI 2.508-22.785; P < 0.001). The median recurrence-free survival was 22.0months for the adjuvant chemoimmunotherapy group, 17.0months for the adjuvant chemotherapy group, and 13.2months for the surgery alone group (P = 0.177); these differences were not significant. The chemoimmunotherapy group was associated with more frequent hematological side effects than the chemotherapy group, but the difference was not statistically significant. Postoperative adjuvant chemoimmunotherapy for resectedpCCA patients showed improved OScompared with adjuvant chemotherapy or surgery alone, and further prospectively randomizedcontrolledtrials are necessary to validate these results.

A Real-World Analysis of Immune Checkpoint Inhibitor-Based Therapy After Osimertinib Treatment in Patients With EGFR-Mutant NSCLC

IntroductionThe use of immune checkpoint inhibitors (ICIs) with chemotherapy has increased the survival of patients with advanced NSCLC. Nevertheless, the efficacy of ICI treatment for NSCLC with EGFR mutations is limited. Previous studies have not evaluated the efficacy of ICI treatment after osimertinib treatment in real-world settings. MethodsThis study performed a retrospective analysis of the association between clinical characteristics and ICI efficacy in patients with EGFR-mutant NSCLC treated with ICIs after osimertinib treatment at 12 institutions in Japan from March 2016 to March 2021. ResultsAmong 80 patients with EGFR-mutant lung cancer, 42 received ICI monotherapy and 38 received chemoimmunotherapy. In the chemoimmunotherapy group, the progression-free survival (PFS) was significantly longer in the group that exhibited PFS more than 10 months with osimertinib than in the group that exhibited PFS less than or equal to 10 months with osimertinib (8.4 mo versus 3.8 mo, p = 0.026). Nevertheless, there was no significant difference in PFS in the ICI monotherapy group (1.7 mo versus 1.5 mo, p = 0.45). Regardless of the EGFR mutation subtype, PFS of osimertinib treatment was a predictor of the PFS of chemoimmunotherapy (exon 19 deletion mutation: p = 0.03 and exon 21 L858R mutation: p = 0.001). ConclusionsThe PFS of osimertinib might be a predictor of PFS of chemoimmunotherapy in patients with EGFR-mutant NSCLC. Further clinical investigations on the predictors of efficacy of administering ICIs after osimertinib treatment are required.

Real-world Clinical Outcomes of First-Line Ibrutinib or Chemoimmunotherapy in Patients with Chronic Lymphocytic Leukemia by Risk Status.

IntroductionCertain genetic features in chronic lymphocytic leukemia (CLL) are associated with inferior outcomes after chemoimmunotherapy (CIT). This retrospective study evaluated treatment patterns and clinical outcomes of patients with CLL, stratified into high-risk and non-high-risk groups, who received first-line ibrutinib or CIT therapy.MethodsHigh-risk group included confirmed presence of del(17p), del(11q), unmutated IGHV, TP53 mutations, or complex karyotype. Weighted high-risk ibrutinib and CIT groups were compared for treatment effects using inverse probability of treatment weighting. Hazard ratios [95% CI] (HR) for time to next treatment (TTNT) were analyzed using Kaplan–Meier curves.ResultsBendamustine/rituximab was the most common CIT regimen initiated for high-risk patients. During the available follow-up (median 34–35 months), 74.7% of the weighted high-risk ibrutinib group received only one line of treatment, compared with 47.2% of the weighted high-risk CIT group. The most common second-line treatment was ibrutinib for those in the CIT groups and venetoclax for the ibrutinib groups. The weighted high-risk ibrutinib group had a significantly longer TTNT (median not reached) than the weighted high-risk CIT group (median 34.4 months) and was 54% less likely to start a new treatment (HR 0.5 [0.3–0.6], P < 0.010). Among CIT-treated groups, high-risk patients had significantly shorter median TTNT than non-high-risk patients (P < 0.010). However, within the ibrutinib-treated groups, the median TTNT was similar between high-risk and non-high-risk patients (HR 2.2 [1.0–5.0]; P = 0.060).ConclusionThis study found that first-line single-agent ibrutinib therapy was associated with significantly longer TTNT than CIT regimens in real-world patients with high-risk CLL. The results support the use of ibrutinib in high-risk patients.Infographic Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01991-5.