Median OS Of Patients Research Articles

Long-term real-world evidence of CPX-351 of high-risk AML patients identified high rate of negative MRD and prolonged OS

CPX-351 has been approved for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). No extensive data are available on MRD and long-term clinical outcome using CPX-351 in AML in real-life. We retrospectively collected data from 168 patients in 36 centers in France and Italy who had received one or two cycles of induction with CPX-351. All patients were older than 18 years and had newly diagnosed, untreated t-AML or MRC-AML. With a median follow-up of 3 years, median OS was 13.3 months. Median OS was 20.4 months vs. 12.9 months for patients with MRD below or above 10-3, respectively (p=0.006). In a multivariate analysis, only MRD >10-3 was associated with a poorer OS (hazard ratio [HR]=2.6, 95% CI 1.2-5.5, p=0.013). We also observed a trend towards a better median OS in patients who underwent HSCT with MRD <10-3 (not reached vs. 26.0 months, p=0.06). Achievement of MRD negativity contributed to the improvement of OS in the overall population and, maybe, in transplanted patients. These data provide the rationale for the two ongoing studies evaluating CPX-351 vs. 7+3 in non-MRC-AML and non-t-AML using MRD as the primary endpoint for ALFA-2101 phase II clinical trial and event-free survival for AMLSG 30-18 phase III clinical trial. Funding: Any

Abstract PO1-06-05: Heterogeneity and prognostic characteristics of HER2-low breast cancer: A retrospective analysis of patients with HER2-negative metastatic breast cancer

Abstract Background: It remains uncertain as to whether low levels of HER2 positivity have any prognostic implications in breast cancer patients, whether HER2 levels can be inconsistent between primary tumors and metastatic lesions in individuals with advanced HER2-negative breast cancer, and how such inconsistencies may impact patient prognosis. Methods: A retrospective analysis of advanced breast cancer patients admitted to our hospital from from January 1st, 2010 to January 1st, 2019 was performed, with all patients that underwent at least one metastatic lesion biopsy being screened. The hormone receptor (HR) and HER2 profiles of both primary and metastatic lesions from these patients were confirmed, and HER2-positive patients (HER2 3+ immunohistochemistry [IHC] results or HER2 2+ IHC results with positive in situ hybridization [ISH] results) were excluded from further analyses. To examine the prevalence of HER2-low status across primary and metastatic cancers, the current study set out to detect inconsistencies between these two tumor compartments with respect to HER2-low status and to examine the prognostic implications of these findings in patients. Results: The median follow-up duration for this study at the cutoff date (December 31, 2021) was 49.3 (45.8-52.8) months. The current study examined 1,031 participants with HER2 and HR status data from both primary and metastatic tumors. The proportion of HER2-low expression was significantly higher in metastatic lesions than primary tumors (34.7% vs 25.7%), with a corresponding drop in the proportion of HER2-zero metastatic lesions (FIGURE 1). In a multivariate analysis, HER-2 upregulation was linked to HR status, which was established as an independent influencing factor, with such upregulation being most common in HR-positive individuals (P= 0.004). With respect to HER2 status of primary lesions, the medianl survival of patients in the HER2-zero was similar to HER2-low patients, regardless of HR status [44.8 months (95% CI 38.2-54.1) vs 41.5 months (95% CI 35.0-48.0)] (P = 0.954)(FIGURE 2A). However, when the HER2 status of metastatic lesions was examined, patients with HER2-low expression had a greater median OS than HER2-zero patients [47.6 months (95% CI 39.6-48.0) vs. 32.2 months (95% CI 24.6-40.0)] (P &amp;lt; 0.001)(FIGURE 2B). The median OS of patients that exhibited HER2 upregulation (zero→low) was longer than that of patients without such upregulation (zero-zero) (55.8 months (95% CI 45.0-66.6) vs. 32.4 months (95% CI 23.8-41.0)) (P &amp;lt; 0.001)(FIGURE 3A). Among HR-positive patients, HER2 upregulation was associated with significantly prolonged OS relative to patients without such upregulation [56.6 months (95% CI 44.6-68.6) vs. 41.7 months (95% CI 31.1-52.3)] (P=0.006)(FIGURE 3B), whereas survival outcomes were similar in these two groups in the HR-negative subgroup [44.8 months (95% CI 25.6-64.0) and 25.3 months (95% CI 20.4-30.3)] (P=0.103)(FIGURE 3C). However, independent of HR status, the median OS of patients who had HER2 downregulation (low→zero) was similar to those without downregulation (low→low)(FIGURE 3 D, E, F). Conclusion: These results support inconsistencies in HER2-low expression status between primary and metastatic lesions, with low HER2 levels in metastatic tumors being associated with improved survival outcomes. HR-positive patients are more likely to exhibit HER2 upregulation within metastatic lesions and experience corresponding prognostic benefits. Keywords: HER2-low, inconsistency, survival, prognosis, advanced breast cancer Citation Format: Huimin Lv, Min Yan, Mengwei Zhang, Limin Niu, Huiai Zeng, Huihui Sun, Shengnan Zhao, Jing Wang. Heterogeneity and prognostic characteristics of HER2-low breast cancer: A retrospective analysis of patients with HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-05.

Evaluation of the Prognostic Impact of SP263-Evaluated PD-L1 Expression in Patients with Stage III Non-Small Cell Lung Cancer (NSLC) Treated with Radio-Chemotherapy.

The PACIFIC study showed that after radio-chemotherapy, patients with NSCLC derived a benefit in PFS and OS when treated with durvalumab. This effect was limited to patients with a PD-L1 expression of >1%, partly because the outcome in the observational control arm was surprisingly favorable. Thus, it could be speculated that a lack of PD-L1 expression confers a favorable outcome for patients with stage III NSCLC. Clinical data, PD-L1 expression, predictive blood markers, and the outcomes of 99 homogeneously treated patients with stage III NSCLC were retrospectively captured. Statistical analyses using the log rank test were performed. The median OS of patients with an expression of PD-L1 < 1% was 20 months (CI 10.5-29.5) and the median OS of patients with an expression of PD-L1 ≥ 1% was 28 months (CI 16.5-39.2) (p = 0.734). The median PFS of patients with an expression of PD-L1 < 1% was 9 months (CI 6.3-11.6) and the median PFS of patients with an expression of PD-L1 ≥ 1% was 12 months (CI 9.8-14.2) (p = 0.112). The assumption that the lack of PD-L1 expression represents a favorable prognostic factor after radio-chemotherapy vs. PD-L1 expression > 1% was not confirmed.

The correlation between systemic inflammatory markers and efficiency for advanced gastric cancer patients treated with ICIs combined with chemotherapy.

Currently lacking research to explore the correlation between inflammatory markers and the efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in the treatment of advanced gastric cancer. This study is a retrospective study and included patients with advanced gastric cancer who receiving ICIs combined with chemotherapy from January 2020 to December 2022. We analysed the relationship between systemic inflammatory markers and the efficacy of ICIs combined chemotherapy and constructed a clinical prediction model. A nomogram was constructed based on the results of the bidirectional stepwise regression model. A total of 197 patients were enrolled in the training group, with a median follow-up period of time 26 months. Kaplan Meier analysis showed that the median OS of patients with low systemic immune-inflammatory index (SII) and low platelet to lymphocyte ratio (PLR) was superior to those with high SII and PLR. Univariate and multivariate Cox regression analysis showed that SII, NLR, PLR, and N stage as independent prognostic factors for OS. Adding SII to the conventional model improved the predictive ability of the 12-month OS. A total of 95 patients were included in the validation group, and external validation of the SII-based nomogram showed favourable predictive performance. Baseline SII, PLR, and N stage may serve as independent predictive factors for survival outcomes in advanced gastric cancer patients undergoing ICIs combined with chemotherapy. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.

The efficacy of immunotherapy and chemoimmunotherapy in patients with advanced rare tumors: A Turkish oncology group (TOG) study.

The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.

Alteration and significance of serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma: a retrospective study based on LEGEND-2

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.

Primary tumour category, site of metastasis, and baseline serum S100B and LDH are independent prognostic factors for survival in metastatic melanoma patients treated with anti-PD-1.

Prognostic classification of metastatic melanoma patients treated with anti-PD-1 is of great interest to clinicians. We aimed to determine the anti-PD-1 treatment related prognostic performance of demographics, clinical and histological prognostic markers and baseline serum S100B and LDH levels in advanced melanoma. A total of 200 patients with unresectable metastatic melanoma were included in this retrospective study. 34.5% had stage M1c disease and 11.5% had stage M1d disease at the start of therapy. 30% had pT4b primary melanoma. 55.5% had elevated baseline serum S100B levels and 62.5% had elevated baseline serum LDH levels. We analysed the risk of death using univariate and multivariate Cox proportional-hazards models and the median overall (OS) and progression-free (PFS) survival using the Kaplan-Meier estimator. The median follow-up time from the start of anti-PD-1 treatment in patients who were alive at the end of the study (N=81) was 37 months (range: 6.1-95.9). The multivariate Cox regression analysis showed that M1c stage (vs. M1a, p=0.005) or M1d stage at the start of therapy (vs. M1a, p=0.001), pT4b category (vs. pT1a, p=0.036), elevated baseline serum S100B levels (vs. normal S100B, p=0.008) and elevated LDH levels (vs. normal LDH, p=0.049) were independently associated with poor survival. The combination of M1d stage, elevated baseline serum S100B and LDH levels and pT4b category was associated with a very high risk of death (HR 4.72 [1.81; 12.33]). In the subgroup of patients with pT4b primary melanoma, the median OS of patients with normal serum S100B levels was 37.25 months [95% CI 11.04; 63.46]), while the median OS of patients with elevated serum S100B levels was 8.00 months [95% CI 3.49; 12.51]) (p<0.001); the median OS of patients with normal serum LDH levels was 41.82 months [95% CI 11.33; 72.32]), while the median OS of patients with elevated serum LDH levels was 12.29 months [95% CI 4.35; 20.23]) (p=0.002). Our real-world study indicates that the prognostic role of primary melanoma parameters is preserved in anti-PD-1 treated stage IV patients. Furthermore, there seems to be perspective in combining clinical, histological and serum prognostic markers in a prognostic model.

Improved Survival Outcomes in Patients With MET-Dysregulated Advanced NSCLC Treated With MET Inhibitors: Results of a Multinational Retrospective Chart Review

BackgroundWe evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET-dysregulated metastatic non–small-cell lung cancer (NSCLC) in a real-world setting. Patients and MethodsThis was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET-dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms. ResultsOverall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations (METex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for METex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the METex14 cohort; 13% in the MET-amplified only cohort). In the METex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET-amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479). ConclusionsMET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET-dysregulated NSCLC.

Different risk and prognostic factors for liver metastasis of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.

The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population. Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan-Meier method. In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively. De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.

Abstract CT200: Updated PFS &amp; OS from the phase Ib study of TQB2450 alone/with Anlotinib in previously treated advanced non-small cell lung cancer

Abstract Background: At the interim analysis (data cutoff Oct 14, 2021) of this study (NCT03910127), TQB2450 plus anlotinb group significantly improved mPFS versus TQB2450 alone in chemotherapy treated patients with advanced NSCLC without driver gene alterations (6.9 months vs 2.7 months). We report an updated PFS, OS and safety results for this study. Method: This is a multicenter, randomized, double-blind, phase Ib study. Adult patients with histologically or cytologically-confirmed stage IIIB or IV NSCLC who had wild-type EGFR/ALK and at least one line of prior systemic therapy or being intolerable of chemotherapy were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or anlotinib 10 or 12 mg. The primary end point was PFS and secondary endpoints included safety and OS. Results: Between July. 2019 and March. 2021, 101 pts were enrolled. 33 patients were randomly assigned to TQB2450 plus placebo and 68 patients to TQB2450 plus anlotinib. As of 19 September 2022, The median follow-up was 26.3 months. The median PFS (7.3 months, 95% CI 5.3-11.0) for TQB2450 plus anlotinib was significantly longer than that for TQB2450 plus placebo group (2.8 months, 95% CI 1.4-4.7) (HR 0.39, 95% CI 0.23-0.64; P=0.0001) (Table). In patients with PD-L1 ≥ 1%, the mPFS was 17.9 months (95% CI 5.8-31.1) in TQB2450 plus anlotinib 12 mg, which was numerically higher than that in TQB2450 plus anlotinib 10 mg. The median OS of patients with PD-L1 ≥ 1% for TQB2450 plus anlotinib 12 mg was numerically higher than that in TQB2450 plus anlotinib 10 mg (32.2 months vs 21.8 months). Grade 3 or higher TRAEs occurred in 50.0% of the patients in TQB2450 plus anlotinb and in 12.1% of those in TQB2450 plus placebo. Conclusions: In this updated analysis with longer follow-up, TQB2450 combined with anlotinib continues to demonstrate overall efficacy and manageable safety profiles in chemotherapy treated patients with advanced NSCLC without driver gene mutations. TQB2450 TQB2450+Anlotinib 10mg TQB2450+Anlotinib 12mg TQB2450+Anlotinib mPFS n 33 34 34 68 Censor, n (%) 7 (21.2) 9 (26.5) 8 (23.5) 17 (25.0) Median (95%CI) 2.8 (1.4-4.7) 7.0 (4.5-14.5) 8.7 (4.1-11.4) 7.3 (5.3-11.0) HR (95%CI) 0.37 (0.21-0.66) 0.40 (0.22-0.70) 0.39 (0.23-0.64) P value 0.0006 0.0001 mPFS (PD-L1≥1%) n 19 19 19 38 Censor, n (%) 3 (15.8) 6 (31.6) 7 (36.8) 13 (34.2) Median (95%CI) 2.1 (1.3-7.2) 7.0 (2.1-19.4) 17.9 (5.8-31.1) 8.6 (5.3-22.8) HR (95%CI) 0.35 (0.16-0.77) 0.29 (0.13-0.64) 0.32 (0.16-0.63) P value 0.0023 0.0006 mOS n 33 34 34 68 Censor, n (%) 12 (36.4) 14 (41.2) 12 (35.3) 26 (38.2) Median (95%CI) 15.3 (6.6-20.5) 20.6 (8.6-25.8) 14.7 (10.0-32.2) 17.9 (10.5-23.2) HR (95%CI) 0.78 (0.42-1.44) 0.84 (0.46-1.53) 0.81 (0.48-1.37) P value 0.7157 0.4329 mOS (PD-L1≥1%) n 19 19 19 38 Censor, n (%) 5 (26.3) 7 (36.8) 8 (42.1) 15 (39.5) Median (95%CI) 15.7 (7.8-21.0) 21.8 (7.1-NR) 32.2 (14.2-33.6) 21.8 (14.2-33.6) HR (95%CI) 0.72 (0.33-1.58) 0.63 (0.28-1.40) 0.67 (0.34-1.32) P value 0.4900 0.2479 Citation Format: Baohui Han, Kai Li, Qiming Wang, Ying Cheng, Lei Yang, Yueming Li. Updated PFS &amp; OS from the phase Ib study of TQB2450 alone/with Anlotinib in previously treated advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT200.

Clinical and prognostic utility of ALBI versus Child-Pugh score in a Mexican population with hepatocellular carcinoma.

517 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The assessment of liver function is crucial in determining the prognosis of patients. Aim: To compare the utility of the ALBI and CHILD-PUGH scores in predicting the prognosis and treatment of patients with hepatocellular carcinoma at the National Cancer Institute, Mexico. Methods: Retrospective, observational study. Included patients diagnosed with HCC and treated at the National Cancer Institute 2008-2021. Statistical analysis included: X2 and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance was assessed when p was bilaterally &lt;0.05. Results: A total of 315 patients diagnosed with HCC were included, mostly male (61%) with a median age of 67 years, mostly in the advanced stages of the disease (90%). Regarding liver functionality scores, of the patients who were scored in CHILD-PUGH-A5 (n=124), 53% were in ALBI G1, while 47% scored ALBI G2. Regarding the CHILD-PUGH-A6 group (n=92) only 71% of patients scored ALBI G2, and among CHILD-PUGH-B7 score (n=55) patients, only 13% scored in the ALBI G3 group (p&lt;0.001). In survival analysis, CHILD-PUGH-A5 patients had a median OS of 40 months, while CHILD-PUGH-A6 patients showed a median OS of 11 months (p&lt;0.001). Patients with a CHILD-PUGH-B7 score showed a median OS of 10 months compared to patients with a CHILD-PUGH-B8 score who showed a median OS of 4 months (p=0.93). Among ALBI score, G1 patients did not reach median OS, while the median OS of patients with G2 and G3 was 13 and 4 months respectively (p&lt;0.001). At Univariate analysis, histology (HR:1.22; p=0.021), bilirubin (HR:1.12; p&lt;0.001), albumin (HR:0.33; p&lt;0.001), CHILD-PUGH (HR:1.27; p&lt;0.001), ALBI (HR:2.91; p&lt;0.001), ECOG (HR:1.82; p&lt;0.001), surgery (HR:2.24; p=0.029) and systemic treatment (HR:2.57; p&lt;0.001) showed statistical differences. While only albumin (HR: 0.45; p=0.027), ECOG (HR: 1.49; p=0.006), systemic treatment (HR: 1.78; p=0.026) and ALBI score (HR: 1.71; p=0.032) remained predictors of OS. Conclusions: The study demonstrates that ALBI score presents a better prognostic and liver function stratification than CHILD-PUGH score in Mexican population.

Impact of cytogenetic abnormalities in symptomatic multiple myeloma; a Japanese real-world analysis from Kansai Myeloma Forum

To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis.

Targeted immunotherapy efficacy analysis in patients with relapsed/refractory B cell acute lymphocytic leukemia

Objective: Comparison of conventional chemotherapy and immunotargeted therapy efficacy in patients with relapsed/refractory (R/R) acute B cell leukemia (B-ALL) . Methods: The clinical data of 212 patients with R/R B-ALL in the Affiliaed Cancer Hospital of Zhengzhou University from January 2008 to July 2020 were analyzed retrospectively to compare the response rate and survival time difference between conventional chemotherapy and immunotargeted therapies (antiCD19 CAR-T and CD3CD19 bi-specific antibody blinatumomab) , and to explore the related factors affecting prognosis. Results: The CR rate of patients with R/R B-ALL treated with anti-CD19 CAR-T cells was 80.4% , patients treated with blinatumomab was 62.5% , and patients treated with chemotherapy was 38.6% . There was significant difference in the CR rate among the three therapies (P<0.001) . CAR-T cells 1-year OS rate was 41.5% , which was significantly higher than that of the chemotherapy group (10.3% ) (P<0.001) . The 1-year PFS rate of CAR-T cells (30.1% ) was also significantly higher than that of the chemotherapy group (9.7% ) (P<0.001) . The median OS of patients with bridging allo-HSCT after CR treatment by CAR-T cells was 18.5 months, which was higher than that of patients without allo-HSCT (8 months) (P=0.027) . The median PFS of patients with allo-HSCT was 17 months, which was higher than that of patients without allo-HSCT (4 months) (P=0.001) . The 1-year OS rate of patients treated with blinatumomab was 14.3% , which was higher than that of the chemotherapy group (10.3% ) (P=0.018) . The 1-year PFS rate (14.6% ) was also higher than that of the chemotherapy group (9.7% ) (P=0.046) . The median OS and median PFS of patients with bridging allo-HSCT were 13 and 11 months, respectively, which was higher than that of patients without allo-HSCT (9.5 and 6 months) . The cytokine release syndrome (CRS) incidence in patients with R/R B-ALL treated with anti-CAR-T cells was 89.8% . Grades 3-4, grade 2, and grade 1 CRS were experienced by 30.2% , 11.3% and 58.5% patients, respectively. Only three patients (37.5% ) with blinatumomab developed CRS, all of which were grade 1. Conclusion: The response rate and survival rate of patients with R/R B-ALL treated with CD19 CAR-T cells and blinatumomab were significantly better than those treated with conventional chemotherapy.

RADT-07. RADIOGRAPHIC “NECROSIS" FOLLOWING SINGLE-FRACTION SRS AND IMMUNE CHECKPOINT INHIBITION IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH BRAIN METASTASES: AN INTERNATIONAL MULTICENTER STUDY

Abstract OBJECTIVE Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRIC) are a frequently observed clinical manifestation and are commonly classified as radiographic radiation necrosis. However, these findings are not well characterized and may predict for response to SRS and ICI. METHODS The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRIC were determined based upon MRI, PET/CT, or MR spectroscopy and a consensus by local clinical providers was required. RESULTS The analysis included 697 patients with 4,536 brain metastases across 11 institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years, 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% were non-small cell lung cancer, melanoma, and renal cell carcinoma (RCC) histology, respectively. TRIC were observed in 9.8%. On univariable analysis, Karnofsky Performance Status (KPS) (hazard ratio [HR]: 0.98; p &amp;lt; 0.001), presence of TRIC (HR: 0.67; p = 0.03), female sex (HR: 0.67; p &amp;lt; 0.001), and prior resection (HR: 0.60; p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR: 0.98; p &amp;lt; 0.001) and the presence of TRIC (HR: 0.66; p = 0.03) were associated with improved OS. A V12 Gy ≥ 10 cm3 (Odds Ratio [OR]: 2.78; p &amp;lt; 0.001), prior whole brain radiation therapy (OR: 3.46; p = 0.006), and RCC histology (OR: 3.10; p = 0.01) were associated with an increased probability of developing TRIC. The median OS in patients with and without TRIC was 29.0 and 23.1 months, respectively (log-rank p = 0.03). CONCLUSION TRIC following ICI and SRS are associated with a median OS benefit of approximately 6 months. Further prospective study is warranted to further elucidate the role and etiology of this common clinical scenario.

1098P Predictive factors of efficacy to pembrolizumab in advanced NSCLC patients with high PD-L1 expression.

Pembrolizumab represents a first-line option for advanced NSCLC with high PD-L1 expression (≥50%). However, several factors such as antibiotic-exposure, low body mass index (BMI), bone metastases, or ECOG-PS of 2, may influence outcomes from fist-line pembrolizumab. We have evaluated the association between those factors with survival in a cohort of patients with stage IV high PD-L1 expression NSCLC consecutively treated with first-line pembrolizumab. We included 104 patients between May 2011 and January 2022. The median follow-up was 16.32 months (m) [1.71 – 63.90]. Median age was 68 years (y) (45-86), 75% were male, 26% were current smokers, 23.1% had ECOG-PS2, 40.4% BMI<25, 6.7% antibiotic-exposure, 33.7% received a corticosteroid dose higher than the equivalent to 10mg of prednisone (>10mg PDNe), 57.7% Proton Pump Inhibitors and 83.7% received treatment beyond progression. 7.7% had complete response (CR) as best response, 43.3% had partial response (PR), 15.2% had steable disease (SD), 22.1% had progression disease (PD). Overall Response Rate (ORR): 51%. The median OS and PFS in the overall population were 22.1 m (95% CI, 11.2-33.0) and 11.84 m (95% CI, 4.49-19.19), respectively. The median OS in patients with a ECOG 0-1, CR/PR as best response, receiving treatment beyond progression and without corticosteroid exposure was significantly longer (p<0.0001) (Table). No differences in OS were observed according to the use of Proton Pump Inhibitors, BMI or smoking habit.Table: 1098PECOG-PSMedian OSp-valueMedian PFSp-value0Not reached (NR)26.03 (11.81-40.26)124.55 (18.34-30.76)14.45 (3.48-25.43)22.13 (1.39-2.87)<0.00010.71 (0.42-1.00)<0.0001>10mg PDNeYes3.13 (0.0-9.33)3.94 (1.26-6.61)No24.55 (19.77-29.33)0.00316.32 (7.71-24.94)0.100Proton Pump Inhibitor exposureYes13.71 (1.75-25.67)16.32 (3.95-28.70)No24.55 (4.87-44.22)0.20511.84 (3.71-19.96)0.939Best responseCRNRNRPRNR32.45 (19.82-45.08)SD11.87 (8.50-15.24)4.42 (2.80-6.04)PD4.77 (2.20-7.35)<0.00012.68 (0.0-5.56)<0.0001Treatment beyond progressionYes31.84 (13.49-50.19)14.45 (3.44-25.47)No10.74 (8.54-12.94)0.0013.94 (2.52-5.35)0.001 Open table in a new tab ECOG 0-1, not receiving exposure, CR/PR as best response and receiving treatment beyond progression were predictive of better outcome to pembrolizumab in advanced NSCLC patients with high PD-L1 expression.

Non-invasive early prediction of immune checkpoint inhibitor efficacy in non-small-cell lung cancer patients using on-treatment serum CRP and NLR.

We determined the clinical relevance of early C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) change in blood as surrogate markers of pro-tumor inflammation (PTI) for predicting clinical outcome of programmed cell death (PD)-1/programmed cell death ligand (PD-L) 1 inhibitor treatment in non-small-cell lung carcinoma (NSCLC). We retrospectively reviewed NSCLC patients treated with anti-PD-1 or PD-L1 inhibitors. Early CRP change was defined as the ratio of 6weeks CRP to baseline CRP, and early NLR change was defined as that of the 6weeks NLR to baseline NLR. PTI index was determined by combinatorial evaluation of early CRP change and early NLR change, PTI index low: both of these were low, intermediate: either of these was low, high; both of these were high. The study included 217 patients. Early CRP change and early NLR change were both associated with PFS and OS. The combinatorial evaluation using these two markers enabled the clear stratification of PFS and OS. The median PFS in patient with PTI index low was 13.9months, while the median PFS in those with PTI index high was 2.5months (p < 0.01, log-rank test). The median OS in patients with PTI index low was not reached; the median OS in those with PTI index high was only 15.4months (p < 0.01, log-rank test). The combinatorial early CRP change and early NLR change as PTI biomarkers have clinical potential in identifying NSCLC patients who can achieve a durable response and long-term survival using PD-1/PD-L1 inhibitors.

Management and outcomes of hydronephrosis in patients with metastatic extramammary Paget's disease: A retrospective analysis.

Hydronephrosis in extramammary Paget's disease (EMPD) with distant metastasis (metastatic EMPD) has been observed in medical practice; however, its prognosis remains unclear. Retrospective analyses were performed to assess the management and outcomes of hydronephrosis in metastatic EMPD. During a follow-up of 44 patients with metastatic EMPD, 13 (30%) developed hydronephrosis. Ten (77%) of the 13 patients with hydronephrosis had impaired renal function (estimated glomerular filtration rate: <60 ml/min/1.73m2 ), and ureteral stents were placed in every patient with impaired renal function. The stent was placed successfully in all 10 patients, and their renal function recovered within a median period of 7 days. Importantly, each of these patients continued chemotherapy, and none of them experienced stent failure. The median overall survival time (OS) in patients with metastatic EMPD and hydronephrosis (n=13) was 7.8 months. Treatment for hydronephrosis was not a significant factor for OS, and median OS in patients who underwent ureteral stent replacement (n=10) was 14.7 months. Collectively, our results indicate that hydronephrosis is relatively common, and ureteral stent placement should be considered in cases of metastatic EMPD with hydronephrosis to maintain renal function and continue chemotherapy toward a better prognosis.

Trends of Clinical Outcomes of Patients with Advanced Hepatocellular Carcinoma Treated with First-Line Sorafenib in Randomized Controlled Trials

Background: Sorafenib has consistently served as the control arm in multiple randomized clinical trials (RCTs) evaluating novel therapies for advanced hepatocellular carcinoma (HCC) for more than a decade. Analyzing trends in clinical outcomes of patients treated with sorafenib for the same indication over time offers the opportunity for unique insight into the evolution of clinical trial conduct and potential non-drug factors impacting outcomes. Methods: We identified RCTs in patients with treatment-naïve advanced HCC where sorafenib was compared to another systemic therapy or placebo. We extracted trial-level demographic, clinicopathologic, and outcome data (overall survival [OS], progression-free survival [PFS], objective response rate [ORR], and duration of therapy). Sample-weighted linear regression was used to identify temporal trends with significance set at p ≤ 0.05. Results: Sixteen RCTs (9 phase III and 7 phase II) enrolling 4,086 patients treated with sorafenib were included in the analysis. Included trials enrolled patients from 2005 to 2019. OS has significantly improved by 4.5 months from 2005 to 2019 (p = 0.048) over time. Thirteen studies provided data on PFS using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with no significant change over time (p = 0.69). ORR assessed by RECIST 1.1 has significantly improved by 6.0% over time (p = 0.003). Median duration of therapy with sorafenib has decreased by 53% since the enrollment of the first clinical trial in 2005, from 23.1 weeks to 12.2 weeks (p = 0.0037). There was no significant change in patient demographics were identified over time to explain the OS findings. Conclusion: The median OS of patients with advanced HCC treated with sorafenib has improved significantly over 15 years. At the same time, the median duration of therapy with sorafenib has decreased. The reason for these findings was not explained by changing demographics of patients enrolled in these trials and has implications for ongoing clinical trials.

P-160: Efficacy and safety of induction therapy with IAd versus IRd regimen in fragile elderly patients with newly diagnosed multiple myeloma: results of a prospective multicenter clinical trail

<h3>Background</h3> Fragile elderly patients with multiple myeloma (MM) have low survival rate due to complications, poor tolerance and complianceand lack of effective treatment. This prospective multicenter non-randomized controlled study designed to assessment the efficacy and safety of IAd versus IRd in fragile elderly NDMM. <h3>Methods</h3> This ongoing trial is conducted at 14 hospitals. Inclusion criteria was aged ≥ 65 years, IMWG GA score ≥ 2 or Mayo geriatric vulnerability scoring system defined as vulnerable. Patients with acute cardiovascular and cerebrovascular events were excluded. Schemes included IAd (ixazomib 4mg d1,8,15, liposome doxorubicin 40mg d1,dex 20mg d1,8,15,22), IRd (ixazomib 4mg d1,8,15, lenalidomide 25mg d1-14, dex 20mg d1,8,15,22), in 4-week cycles. For patients with effective response (≥ PR) after 6 to 8 cycles, Id maintenance initiated until progression. The study was powered for a primary endpoint of ORR,with PFS,OS,toxicity,health-related Qol as secondary endpoints. This study planned to enroll 120 patients, 60 in each group (chiCTR1900024917). <h3>Results</h3> From Oct 2019 to May 2021, 95 patients were enrolled, median age 71(65-88) yrs, 29.5% of patients ≥75 yrs,18.9% of patients with renal insufficiency(eGFR < 30ml/min, n=13).Efficacy was evaluated in 89 patients,6 were not evaluated, of them,1 had not completed first cycle,2 had dropped out after first cycle,and 3 died in the first course. All patients with renal insufficiency (except for one case), paraplegia, or bedridden were enrolled in IAd group. At a median follow-up of 10 mons (1-20), total ORR was 80.9%, with 80.9% (38/47) in IAd and 81.0% (34/42) in IRd. Median PFS was 16 mons in IAd and was not achieved in IRd. Median OS was not achieved in both two groups,with 12 mon-OS at 81.0%. Cytogenetic high-risk was defined by t(4;14),t(14;16),t(14;20),del(17p) or 1q21 amplification.64.2% of patients stratified as high-risk, 21.0% of patients had ≥ 2 high-risk cytogenetic, median OS was 14 mons, while the median OS of patients with 1 or none high-risk genetic was not achieved (p=0.05).9.5% patients developed hematological grade 3 or above,13.7% patients developed gastrointestinal AE above grade 3 (IAd, n=10; IRd, n=3),13.7% patients with pneumonia(IAd, n=9; IRd,n=4). IRd regimen saw more serious neurotoxicity,5 patients had delirium, mental disorder or cerebral infarction. Fragile elderly patients are relatively vulnerable to death.16 patients died, included 7 deaths due to progression, 4 early deaths (≤60 days),4 treatment abandonment, and 1 unexplained sudden death. <h3>Conclusion</h3> Overall efficacy and safety results support the use of IAD or IRD as frontline therapy for fragile elderly MM patients. Both regimenswere effective, with an overall response rate of 80.9% and 12-month OS of 81.0%. AE were tolerable. Mortality rate are comparably high in fragile elderly MM patients,it is still a challenge for treatment.

P42.03 Predictive Factors of Response to PD-(L)1 Inhibitors in Patients With Advanced Non-Small Cell Lung and High PD-L1 Expression

Tumor PD-L1 expression is the only validated predictive biomarker in advanced NSCLC patients (pts) treated with PD-(L)1 inhibitors. Analysis of PD-L1 expression by immunohistochemistry has been validated in histological samples. Smoking and overweight have been described as predictive factors of better outcome, whereas bone metastases, antibiotics, corticosteroids and proton pump inhibitors as possible negative predictive factors. The aim of our study was to analyze different potential predictive factors to PD-(L)1 inhibitors in pts with advanced NSCLC and high PD-L1 expression. This retrospective study was carried out in pts with advanced NSCLC and high PD-L1 expression treated with PD-(L)1 inhibitors with median follow-up of 12.8 months [3.6-73.9]. Clinical and histological variables of interest were registered. Kaplan-Meier estimations were used to calculate survival, while the log-rank test was implemented to make comparisons. The impact of variables on survival was assessed through univariate and bivariate analysis. We included 86 pts, the mean age was 66 y [36-84], 24.4% were females, 73.3% were former smokers and 22.1% current smokers, 38,4% presented normal Body Mass Index, 79% pts had non-squamous NSCLC, and 12% pts had cytological sample for PD-L1 determination. 72 (83.7%) pts received monotherapy with PD-(L)1 inhibitor, 4 (4.7%) pts chemotherapy plus PD-(L)1 inhibitor and 10 (11.6%) pts received PD-(L)1 inhibitors with other immunotherapy drug. The median OS and PFS were 23.0 months (95% CI, 13.7 to 32.4) and 9.5 months (95% CI, 2.3 to 16.7), respectively. ORR and DCR in overall patients were 55.6% and 71.5%, respectively. The median OS in complete/partial response vs. stable disease vs. progression disease was not reached vs. 14.0 months (95% CI, 8.1 to 19.8) vs. 4.2 months (95% CI, 2.6 to 8.0), respectively (P<0,001). The median OS in patients receiving treatment beyond progression was not reached vs. 10.4 months (95% CI, 8.2 to 12.6) in patients that stopped treatment (P<0,001). A trend to better results were observed in patients with overweight or smokers, and a trend to worse OS was observed in pts with bone metastasis. No differences in OS were observed according to the tumor sample (cytological vs histological samples). Response to immunotherapy and treatment beyond progression were predictive of better outcome in pts with advanced NSCLC and high PD-L1 expression. No significant differences in survival were observed according to the type of tumor sample or clinical characteristics.