Long-term PFS Research Articles

MRD-negative duration following latest line of therapy predicts long-term PFS in real-world multiple myeloma patients.

MRD-negative duration following latest line of therapy predicts long-term PFS in real-world multiple myeloma patients.

Prognostic Significance of Baseline Clinical and [68Ga]Ga-PSMA PET Derived Parameters on Biochemical Response, Overall Survival, and PSA Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Undergoing [177Lu]Lu-PSMA Therapy.

In this study, we sought to identify the clinical baseline characteristics and pre-therapy 68Ga-PSMA PET derived parameters that can have impact on PSA (biochemical) response, OS and PSA PFS in patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo RLT with [177Lu]Lu-PSMA-617. Various pre-treatment clinical and PSMA PET derived parameters were gathered and computed. We used PSA response as the criteria for more than a 50% decrease in PSA level, and OS and PSA PFS as endpoints. We assessed the collected parameters in relation to PSA response. Additionally, we employed univariable Cox regression and Kaplan-Meier analysis with log rank to evaluate the influence of the parameters on OS and PFS. A total of 125 mCRPC patients were included in this study. The median age was 68 years (range: 49-89). Among the cases, 77 patients (62%) showed PSARS, while 48 patients (38%) did not show PSA response. The median OS was 14 months (range: 1-60), and the median PSA-PFS was 10 months (range: 1-56). Age, prior history of chemotherapy, and SUVmax had a significant impact on PSA response (p<0.05). PSA response, RBC count, hemoglobin, hematocrit, neutrophil to lymphocyte ratio (NLR), alkaline phosphatase (ALP), number of metastases, wbPSMA-TV, and wbTL-PSMA significantly affected OS. GS, platelet count, NLR, and number of metastases were found to have a significant impact on PSA PFS. We have identified several baseline clinical and PSMA PET derived parameters that can serve as prognostic factors for predicting PSA response, OS, and PSA PFS after RLT. Based on the findings, we believe that these clinical baseline characteristics can assist nuclear medicine specialists in identifying RLT responders who have long-term survival and PFS.

Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival.

Prognostic Immunophenotyping in Myeloma Response (PRIMeR) is an ancillary study of minimal residual disease (MRD) assessment for multiple myeloma by next-generation multiparameter flow cytometry (MFC). Patients were enrolled on a three-arm randomized control trial (Blood and Marrow Transplants Clinical Trials Network 0702 Stem Cell Transplant for Myeloma in Combination of Novel Agents [STaMINA]; ClinicalTrials.gov identifier: NCT01109004). Four hundred and thirty-five patients consented to the MRD panel, which included 10 monoclonal antibodies measured via six-color MFC. MRD was measured at baseline/preautologous hematopoietic cell transplant (BL/preAutoHCT), premaintenance (PM), and 1 year (Y1) after AutoHCT with a sensitivity of 10-5 to 10-6. The primary objective was to assess MRD-negative (MRDneg) at 1 year after AutoHCT and progression-free survival and overall survival (PFS/OS). Similar to the STaMINA results, at a median follow-up of 70 months, there was no significant difference in PFS/OS by treatment arm in the PRIMeR patients. MRDneg at all three time points was associated with significantly improved PFS, and MRDneg at Y1 had significantly longer OS. Multivariate analysis of PFS, adjusting for disease risk and treatment arm, demonstrated hazard ratios (HRs) in MRD-positive patients compared with MRDneg patients at BL, PM, and Y1 of 1.55 (P = .0074), 1.83 (P = .0007), and 3.61 (P < .0001), respectively. Corresponding HRs for OS were 1.19 (P = .48), 0.88 (P = .68), and 3.36 (P < .001). Patients with sustained MRDneg or who converted to MRDneg by Y1 had similar PFS/OS. To our knowledge, this first, prospective US cooperative group, multicenter study demonstrates that MRDneg at Y1 after AutoHCT with lenalidomide maintenance is prognostic for improved 6-year PFS and OS. Serial MRD measurements may direct trials to test how further therapy may improve long-term PFS and OS.

382 Precision and Individualized Medicine: Quantification of Brain Cancer Cell Invasion in Confined Microfluidic Spaces Predicts Prognosis

INTRODUCTION: Clinical prognosis of patients with glioblastoma (GBM) is calculated with clinical scores, extent of resection, molecular markers, and tumor subtypes. However, these are often hampered by patient comorbidities, drug toxicity, and other confounding factors. We designed a confined 3D microfluidic technology based on the brain cytoarchitecture by mimicking the diameters of the perivascular spaces and white matter tracts utilized by GBM to invade. METHODS: Patient-derived GBM cell lines (n = 13) were obtained from patients undergoing surgery. After cell culture, the GBM cells’ abilities to migrate and proliferate with MAqCI were evaluated. MAqCI score was calculated via logistic regression. Patients were categorized into low- and high-PFS. Predicted scores were correlated with the clinical status of patients. Cells were treated with gold standard and experimental drugs, and scores were calculated to predict response to treatment. RESULTS: MAqCI Predicted PFS with 83% accuracy, 84.6% sensitivity, and 75% specificity and allowed for the classification of short- and long-PFS (*p = 0.035). Survival based on MAqCI scores separated by short-term (n = 5) and long-term (n = 8) PFS, showed a significant difference between groups (**p = 0.002). After treatment with gold-standard therapy, responder patients were identified based on changes in the MAqCI score. RNAseq of highly motile cells isolated from MAqCI allowed for the identification of druggable targets. An FDA-approved antidepressant against the adrenomedullin gene was selected for MAqCI testing. Changes in MAqCI score after treatment allowed for the identification of responder patients. CONCLUSIONS: Cell invasion properties are directly correlated with patient prognosis. MAqCI could be utilized clinically as a companion assay for predicting tumor recurrence and selecting drugs for individualized GBM treatment.

Cost-effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for the treatment of 3L + relapsed/refractory large B-cell lymphoma in the United States: incorporating longer survival results

Aims To provide an update on the cost-effectiveness of the chimeric antigen receptor (CAR) T-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL) among patients who have previously received ≥2 lines of systemic therapy using more mature clinical trial data cuts (60 months for axi-cel overall survival [OS] and 45 months for tisa-cel OS and progression-free survival [PFS]). Methods A partitioned survival model consisting of three health states (pre-progression, post-progression and death) was used to estimate quality-adjusted life years (QALYs) and costs associated with axi-cel and tisa-cel over a lifetime horizon. PFS and OS inputs for axi-cel and tisa-cel were based on a previously published matching-adjusted indirect treatment comparison (MAIC). Long-term OS and PFS were extrapolated using parametric survival mixture cure models (PS-MCMs). Costs of CAR-T cell therapy drug acquisition and administration, conditioning chemotherapy, apheresis, CAR T-specific monitoring, stem cell transplant, hospitalization, adverse events, routine care, and terminal care were sourced from US cost databases. Health state utilities were derived from previous publications. Model inputs were varied using a range of sensitivity and scenario analyses. Results Compared with tisa-cel, axi-cel resulted in 2.51 additional QALYs and $50,185 additional costs (an incremental cost-effectiveness ratio [ICER] of $19,994 per QALY gained). In probabilistic sensitivity analysis (PSA), the ICER for axi-cel versus tisa-cel was ≤$50,000/QALY in 99.4% of simulations and ≤$33,500 in 99% of simulations. Axi-cel remained cost-effective versus tisa-cel (assuming a willingness-to-pay threshold of $150,000 per QALY) across a range of scenarios. Conclusions With longer-term survival data, axi-cel continues to represent a cost-effective option versus tisa-cel for treatment of r/r LBCL among patients who have previously received ≥2 lines of systemic therapy, from a US payer perspective.

Impact of race and ethnicity on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

Non-Hispanic Black patients are disproportionally affected by multiple myeloma (MM) and whether efficacy outcomes after autologous stem cell transplant (ASCT) differ by race and ethnicity remains an area of active investigation. This study included 449 patients enriched with a large proportion of non-Hispanic Black patients and sought to highlight the impact of race and ethnicity on outcomes after HDT-ASCT for patients with newly diagnosed MM. We found induction chemotherapy followed by high-dose therapy-ASCT and maintenance chemotherapy is associated with long-term PFS and OS, regardless of race or ethnicity.

A multicenter retrospective analysis of patients with salivary gland carcinoma treated with postoperative radiotherapy alone or chemoradiotherapy

BackgroundThe aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone. MethodsThis multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model. ResultsThe median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P = 0.009) and PFS (38.7% vs. 10.0%, P = 0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P = 0.032), PFS (P = 0.001), and LRC (P = 0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P = 0.034) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P = 0.039). On multivariate analyses, the use of POCRT significantly predicted superior OS (P = 0.037) and PFS (P = 0.013) for node-positive patients and LRC for patients with R2 resection (P = 0.041) or AdCC (P = 0.005). ConclusionsFor surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC.

Ibrutinib dose modifications for management of cardiac adverse events in patients with B-cell malignancies: Pooled analysis of 10 clinical trials.

7538 Background: Continuous therapy with once-daily ibrutinib (Ibr) is associated with long-term PFS in pts with B-cell malignancies. Dose reduction is a potential AE management approach that may optimize treatment outcomes. We evaluated outcomes with dose reductions in Ibr-treated pts with cardiac AEs. Methods: Data were pooled for Ibr-treated pts from 10 studies of CLL (n=781), mantle cell lymphoma (MCL; n=250), marginal zone lymphoma (MZL; n=63) or Waldenström macroglobulinemia (WM; n=169). Cardiac AEs, initial and recurrent, were identified by preferred terms within the cardiac disorders system organ class. Recurrence was defined as an AE of same or worse grade, and was measured up to 30 days after last dose of ibrutinib or start of next-line therapy, whichever occurred earlier. Results: Overall, 234/1263 pts (19%) had cardiac AEs of any grade. Twelve pts were excluded from the analysis: 9 who had a dose reduction prior to a cardiac AE (0.7%) and 3 who had a fatal cardiac AE with no prior cardiac AE (0.2%). Of the remaining 222 pts with grade 1-4 cardiac AEs, 22 (10%) had Ibr dose reduction to 420 mg (n=3), 280 mg (n=10), or 140 mg (n=9) after a cardiac AE. These pts (n=22) tended to be older (≥75 y: 45% vs 29%), less heavily pretreated (≥1 prior therapy: 45% vs 73%), and with a lower Ibr discontinuation rate (23% vs 48%) than those without dose reduction (n=200). Recurrence of the same cardiac AEs at the same or worse severity was less frequent in pts with dose reductions, both overall (14% vs 18%) and as serious AEs (5% vs 10%). No pt died due to cardiac AE recurrence. Among pts with cardiac AEs who started with the 420 mg Ibr dose (177/222; excludes 45 patients with MCL or MZL who per label start with 560 mg dose), no cardiac AE recurred at same or worse severity in the subset with dose reductions (Table). PFS was not negatively impacted by dose reduction, both overall (n=22; median PFS not reached [NR], 24-mo PFS: 91%), and in those who started with the 420 mg dose (n=18; median PFS NR; 24-mo PFS, 94%). Conclusions: Dose reduction for cardiac AEs may enable pts to continue to benefit from long-term Ibr and mitigate the risk of cardiac AE recurrence or worsening. Clinical trial information: NCT01105247 , NCT01236391 , NCT01578707 , NCT01722487 , NCT01611090 . [Table: see text]

A phase II study of afatinib in combination with pemetrexed and carboplatin in patients with EGFR mutation positive non-squamous, advanced non–small-cell lung cancer (NSCLC) refractory to first-line osimertinib treatment: NEJ025B.

9044 Background: To date, osimertinib has been commonly used as a first-line treatment for EGFR mutated advanced NSCLC. However, the issue of what constitutes effective treatment after osimertinib failure remains．We evaluated treatment with afatinib plus chemotherapy for EGFR mutated NSCLC resistant to osimertinib. Methods: Patients (pts) with EGFRm (Del19 or L858R) after failure of osimertinib treatment were assigned to a regimen of afatinib 20mg daily combined with carboplatin AUC5 mg/ml/min and pemetrexed 500mg/m2 every 3 weeks followed by maintenance treatment with afatinib plus pemetrexed until disease progression or unacceptable toxicity was noted. The primary endpoint was rate of PFS at 6 months after initiation of treatment (6M-PFSR). The threshold was set at 35% and the expected value at 60% (two-sided P-value of 5% and power of 80%). Thirty-one patients were required, and the target number of patients was set at 35 after accounting for ineligible cases. Secondary endpoints were PFS, OS, ORR, DOR, and Safety. In this study, blood samples were collected before and after study treatment and at the time of PD to examine biomarkers using CAPP-SEQ. This biomarker study is ongoing. Results: Between June 7, 2020 and January 19, 2022, 36 pts were enrolled. One patient was found to meet the exclusion criteria, and the efficacy was analyzed in the other 35 patients. The mean age was 70 years, 60% were women, and 54.3% were nonsmokers. The 6M-PFSR, the primary endpoint, was 57.1%. The confidence interval of 39.3%-71.5% exceeded the threshold of 35%, and the study met its primary endpoint. Notably, 24.1% of pts had a long-term PFS of 1 year or longer. ORR was 48.6%, DCR was 88.6%, median PFS was 8.2M, median DOR was 5.6 M, and median OS was not reached. By mutation type, ORR were similar for Del19 and L858R (46.7% and 50.0%, respectively), but median PFS tended to be longer for Del19 compared to L858R (9.6M and 5.2M, respectively). Pts who responded to previous osimertinib therapy (CR and PR: n = 29) tended to have longer mPFS compared to non-responders (SD, PD, and NE: n = 6) (8.5M and 5.8M, respectively). Adverse events due to TKI and chemotherapy were observed. Diarrhea (52.8%), anorexia (44.4%), fatigue (33.3%), and paronychia (36.1%) were the most frequent adverse events, and these adverse events were predictable and manageable. Interstitial pneumonia developed in three patients (8%), one of whom was the only death in the study. Conclusions: The combination of afatinib and the platinum doublet showed satisfactory efficacy with manageable adverse events in tumors refractory to osimertinib, and met its primary endpoint. OS follow-up and biomarker analyses are still ongoing. This regimen is expected to be a candidate for second-line therapy after osimertinib. Clinical trial information: jRCTs021200005 .

Comparison of atezolizumab monotherapy to docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy.

e21157 Background: Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy (IO) were excluded from these trials. The preferred subsequent therapy for these patients remains to be docetaxel +/- ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in IO-pretreated patients are unknown. Methods: We conducted a retrospective study of all patients with locally advanced/metastatic NSCLC who were pretreated with IO at Mayo Clinic Florida/Rochester in 2016 - 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. Kaplan-Meier method and log-rank test were used for survival analysis. Results: Among 169 patients included, 51.5% were female, 91.7% were Caucasian. The median age was 67 (35 – 92). The histology was predominantly adenocarcinoma (76.3%). The most common metastatic sites were bone (51.5%), followed by CNS (44.4%). The median number of prior therapies was 2 (1 – 8). Pembrolizumab was the most used prior IO (87%), followed by durvalumab (10.7%) and nivolumab (8.3%). 13.6% (n = 23), 49.1% (n = 83), and 37.2% (n = 63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. PFS was improved in the Atezo group compared with Doce group (median PFS 3.9 vs. 3.7 months, HR 0.57, 95% CI 0.37 – 0.87, p = 0.015*). Notably, a prominent percentage of patients in the Atezo group appear to have long-term PFS benefits, demonstrated by 1-year PFS rates of 26.1%, 3.6%, and 4.8% (p = 0.003**), and 2-year PFS rates of 17.4%, 0%, and 0% (p = 0.002**), in the Atezo, Doce, and Doce+Ram groups, respectively. The median OS (months) in the Atezo, Doce, and Doce+Ram groups were 17.5, 7.6, and 11.5, respectively; and were 29.5, 7.2, and 6.9, respectively in the PD-L1 &gt; 50% subgroups. The Atezo group showed significantly greater OS improvement compared with the Doce group (HR 0.42, 95% CI 0.26 – 0.66, p = 0.001**). This benefit appears greater and remains statistically significant in the PD-L1 &gt; 1% (HR 0.39, 95% CI 0.22 – 0.71, p = 0.005**) and PD-L1 &gt; 50% (HR 0.37, 95% CI 0.15 – 0.91, p = 0.022*) subgroups. 5 of 23 (21.7%) patients in the Atezo group developed immune-related adverse events. 3 patients were grade 3 or 4. No grade 5 event. Conclusions: We observed statistically significant and clinically meaningful PFS and OS benefits of atezolizumab monotherapy compared with docetaxel in patients with advanced NSCLC who were pretreated with IO. The OS benefits of atezolizumab over docetaxel +/- ramucirumab was greater in PD-L1 &gt; 1% and PD-L1 &gt; 50% subgroups. Atezolizumab appears to be tolerable in IO-pretreated patients. These findings need to be verified in a prospective study.

TTFields Prolonged the PFS of Epithelioid Glioblastoma Patient: A Case Report

Epithelioid glioblastoma (EGBM, classified as glioblastoma, IDH wild type, grade 4 according to the fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) (WHO CNS5)) is a highly aggressive malignancy, with a median progression-free survival (mPFS) of about 6 months in adults. The application of tumor-treating fields (TTFields, possessing anti-cancer capabilities via anti-mitotic effects) in the maintenance of temozolomide (TMZ) chemotherapy showed a benefit for prolonging the mPFS of newly diagnosed glioblastoma (GBM) for patients for up to 6.9 months in the EF-14 clinical trial (NCT00916409). However, studies focusing on the effect of TTFields in EGBM treatment are very limited due to the rarity of EGBM. Here, we have reported a case of a 28-year-old male (recurrent left-sided limb twitching for 1 month and dizziness for 1 week) diagnosed with EGBM. A right frontal lobe occupancy was detected by magnetic resonance imaging (MRI), and a total tumor resection was performed. Meanwhile, a postoperative histopathology test, including immunohistochemistry and molecular characterization, was conducted, and the results revealed a BRAF V600E mutation, no co-deletion of 1p and 19q, and negative O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Then, chemoradiotherapy was conducted, and TTFields and TMZ were performed sequentially. Notably, a long-term PFS of 34 months and a Karnofsky Performance Scale (KPS) of 90 were achieved by the patient on TTFields combined with TMZ, whose average daily usage of TTFields was higher than 90%.

Abstract 3224: TTFields-prolonged the PFS of epithelioid glioblastoma patient: a case report

Abstract Epithelioid glioblastoma (EGBM, classified as glioblastoma, wild type, grade IV according to 2021 WHO CNS5 classification of neurological malignancies) is a highly aggressive malignancy, the median progression-free survival (mPFS) of which is about 4.0 months. Although, the introduction of tumor treating fields (TTFields, possessing anti-cancer capability via anti-mitotic effects) in the maintenance of TMZ chemotherapy was demonstrated beneficial for prolonging the mPFS of GBM patients to 6.9 months in the EF-14 clinical trial, studies centering on the significance of TTFields in EGBM treating are very limited due to the rarity of EGBM. Therefore, a 28-year-old patient (male, recurrent left-sided limb twitching for 1 month and dizziness for 1 week) was chosen as a clinical trial participant. A right frontal lobe occupancy was detected based on magnetic resonance imaging (MRI), and total tumor resection was performed on the patient. Meanwhile, postoperative histopathology test, including immunohistochemical and molecular characterization, was conducted and the results revealed a BRAF V600E mutation, no codeletion of 1p and 19q, and negative MGMT promoter methylation, which confirmed EGBM. In this context, chemoradiotherapy was conducted on the patient at first, and then concurrent TTFields and TMZ was performed. Notably, a long-term PFS of 33 months and KPS score of 90 were achieved over the patient upon TTFields combined TMZ, whose average daily usage of TTFields was higher than 90%. This clinical case corroborated the importance of TTFields in EGBM treating, and the higher compliance of TTFields is more beneficial for EGBM patient without additional side effect. YD, QW contributed equally to this work. Citation Format: Yuxuan Ding, Qiang Wang, Feijiang Wang, Nan Wu, Jianrui Li, Xia He, Hao Pan, Lijun Wang. TTFields-prolonged the PFS of epithelioid glioblastoma patient: a case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3224.

Abstract 3252: TTFields combined with temozolomide and immunotherapy show long-term PFS on a GBM patients with multiple negative prognostic factors

Abstract Glioblastoma (GBM) is a common CNS tumor with poor prognosis. The median progression-free survival (mPFS) of standard Stupp regimen was about 6.9 months. The 2-THE-TOP study suggested that a triple regimen of temozolomide (TMZ) combined with pembrolizumab and Tumor treating fields (TTFields) could further prolong the mPFS of newly diagnosed GBM to 12.1 months. Here we report a case showing long PFS from this triple regimen. In October 2019, a 60-year-old female patient was admitted to the hospital due to intermittent dizziness and headache with rapid progression of left limb weakness for more than 10 days. MRI showed a space-occupying lesion in the basal ganglia of the right temporal lobe, with obvious peritumoral edema involving the basal ganglia, posterolateral thalamus, and cerebral foot, with midline shift, demonstrating a high-grade glioma. Total resection of the tumor was performed on October 30, 2019. Pathological diagnosis was glioblastoma, IDH wild type, WHO grade 4. Next generation sequencing showed negative MGMT promoter methylation, TERT promoter mutation, PTEN mutation, CDK4 and EGFR amplification. TMZ concurrent chemoradiotherapy was initiated on November 19, 2019, followed by triple regimen of TMZ adjuvant chemotherapy (200mg/m2), pembrolizumab (200mg VD q3w) and TTFields in March 2020. During this period, the compliance of TTFields remained above 92%, which means the daily duration of TTFields was above 22.08 hours. Regular MRI review showed that the intracranial condition was stable, and there was no interruption of treatment due to treatment-related adverse reactions. No progression was found in the MRI reexamination in April 2022 but TTFields and TMZ chemotherapy were subsequently discontinued for the patient’s personal reasons, however, pembrolizumab monotherapy was maintained. In July 2022 she was hospitalized due to hemiplegia and the tumor recurrence was revealed in MRI, indicating a PFS of 33 months. She underwent tumor resection again and was histologically diagnosed as recurrent GBM on August 2,2022. After surgery, electric field therapy and immunotherapy were resumed. The patient was well recovered with a stable disease at the time of submitting this abstract. This patient had multiple negative prognostic factors of GBM. But under the combined regimen of electric field therapy, immunotherapy and chemotherapy, the disease control was maintained for up to 33 months, which is significantly prolonged compared to historical data of 12.1 months. The patient maintained TTFields for nearly 2 years, and tumor recurrence occurred 3 months after discontinuation of TTFields, indicating that continuous use of TTFields take great importance on disease control. Overall, our case of long-term PFS provides an important reference for the treatment of GBM patients with TTFields combined with immunotherapy and TMZ chemotherapy. Citation Format: Zhiyong Li, Xi'an Zhang, Tianshi Que, Guozhong Yi, Peidong Zhang, Haojie Zheng, Xi Yuan, Songtao Qi, Guanglong Huang. TTFields combined with temozolomide and immunotherapy show long-term PFS on a GBM patients with multiple negative prognostic factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3252.

Notch-Jagged1 signaling and response to bevacizumab therapy in advanced colorectal cancer: A glance to radiomics or back to physiopathology?

The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab. Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor. A positive association was found between NICD and Jag1 expression (p< 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823). These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

The evolving diagnosis and treatment paradigms of multiple myeloma in China: 15 years' experience of 1256 patients in a national medical center.

Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first-line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. Of the 1256 individuals, median age was 64 (range 31-89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light-chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high-risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short- and long-term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7months. Advanced ISS stage, HRCA, light-chain amyloidosis and EMD independently predicted an inferior PFS. First-line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light-chain amyloidosis, and receiving PI/IMiD-based regimen versus PI+IMiD-based regimen independently indicated a poorer OS. In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

Muticenter Retrospective Comparable Study of Prophylactic Versus Preemptive Modified Donor Lymphocyte Infusion for Patients with High-Risk Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Objective: To compare the efficacy and safety of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk acute leukemia Method: Patients with high-risk acute leukemia who received myeloablative conditioning and allo-HSCT during August 1, 2014 to August 30, 2020 were eligible for this study. Pro-DLI was scheduled at three months after HSCT for patients in pro-DLI cohort. In the pre-DLI cohort, patients would stop immunosuppressive drugs and receive pre-DLI immediately after MRD turning positive with morphology remission. Result: Pro-DLI was performed in ninty-five patients while two hundred and six patients were included in the pre-DLI cohort. Thirty-eight patients in the pre-DLI cohort became positive MRD and received pre-DLI. Patients in the pro-DLI cohort achieved a lower cumulative incidence of relapse (CIR) (27.6% versus 37.1%, p=0.027) and comparable overall survival (OS) (65.2% versus 59.3%, p=0.303) comparing with patients in the pre-DLI cohort. The 100-days cumulative incidence of grade III-IV acute graft-versus-host-disease (aGVHD) and chronic graft-versus-host-disease (cGVHD) were comparable between cohorts. Further subgroup analysis of patients who received allo-HSCT at CR1, pro-DLI achieved lower 3-year cumulative incidence of relapse (CIR) (27.6% versus 37.1%, p=0.027) while no benefit in OS (72.2% versus 69.2%, p=0.864) comparing with pre-DLI cohort. On the other hand, pro-DLI significantly decreased the CIR (13.25% versus 28.77%, p=0.044) and increased OS (60.7% versus 42.3%, p=0.022) when compared with pre-DLI in patients who received HSCT beyond CR1. Multivariate analysis demonstrated the strong protective effect of pro-DLI on long-term OS and PFS in patients who received HSCT beyond CR1. Conclusion: From these date, pro-DLI was highly recommended for patients with high-risk features who received allo-HSCT beyond CR1 with significantly decreased incidence of relapse and increased survival rates. Pre-DLI could be chosen by those who received allo-HSCT in CR1 in view of comparable survival rates regardless of higher relapse rates compared with pro-DLI.

Outcome of Tandem CD19/CD20 CAR Therapy with 3-Year Follow-up in R/R B-NHL

Background: Tandem CD19/CD20 CAR T cells, which got two scFvs connected to a single molecule with different antigen specificities simultaneously, not just showed broad antigen coverage, yet additionally had robust antitumour activity in vitro. The best overall response rate was 78% with 70% achieving a CR. Here, we report updated clinical outcomes from this trial. Methods: 87 patients with R/R B-NHL after ≥ 2 lines of therapy (including an anti-CD20 mAb plus an alkylating agent) recruited between 2017.05 and 2020.01, which underwent leukapheresis and conditioning chemotherapy followed by a Tandem CD19/CD20 CAR T cells at doses of 0.5 - 8×106/kg of body weight. The updated follow-up analysis was mainly in median PFS, median OS, and median EFS. Besides, survival status of patients after CAR T failure were also observed in the follow-up data. Results: Up to 2022.5.10, the median follow-up time was 38.3 months, 40 patients (45.98%) still keep ongoing response, and the median PFS was 33.17 months, with 49.52% of 3-year PFS rate; the median EFS was 27.6 months, with 47.51% of 3-year EFS rate. The median OS was not reached, with 68.6% of 3-year OS rate. Nonrelapse mortality was 4.4%. Among 39 patients (44.83%) experienced PD after tandem CD19/CD20 CAR T infusion, best response was 54% CR and 10% partial response (PR); 36% were primary refractory, the median PFS was 6.03 months, and the median OS was 25.2 months. Survival data were statistically analysed for patients after CAR T failure, the median follow-up was 26.77 months , and the median OS was 16.37 months. Conclusions: With 3-year follow-up, Tandem CD19/CD20 CAR T cells demonstrated substantial and continued benefits in patients with r/r B-NHL. High CR rates lead to sustained remission and durability, with a long-term median PFS and high percentage of patients in ongoing response at data cutoff, maintained a manageable safety profile, with no new safety signals. For the patients failure after tandem CD19/CD20 CAR T treatment, other anti-tumor regimens, such as bispecific antibodies, target drugs, immunomodulator, secondary CAR T, radiotherapy and so on, could also appeared to attain efficacy outcomes to improve these patient's survival. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Molecular Response of ≤10% BCR::ABL1IS Is Predictive of Positive Outcomes in Treatment-Resistant Patients with Chronic Phase Chronic Myeloid Leukemia (CP-CML) Treated with Ponatinib from the Phase 2 Optic Trial

Background:BCR::ABL1 mutations are key contributing factors to tyrosine kinase inhibitor (TKI) resistance in patients with chronic myeloid leukemia (CP-CML). Ponatinib is a third-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) designed to potently inhibit BCR::ABL1 with or without any single resistance mutation, including T315I. The Phase 2 OPTIC trial evaluated benefit/risk outcomes of ponatinib using a novel response-based dosing strategy in patients with heavily pretreated resistant CP-CML. In the OPTIC trial, all 3 dosing regimens demonstrated benefit in resistant patients, with optimal benefit/risk outcomes observed in patients who received the response-based dosing of 45 → 15 mg/day. Here we present a post hoc analysis of long-term outcomes (progression-free survival [PFS] and overall survival [OS]) of patients in the OPTIC trial who reached landmark clinical responses (≤1%, >1%-≤10%, and >10% BCR::ABL1IS by Months 3, 6, and 12). Methods: The OPTIC trial design has been previously described (Cortes J, et al. Blood. 2021;138:2042-50). Overall, 99% of patients had treatment-resistant disease; 61% of patients had a best response to their last prior therapy of complete hematologic response or worse; and 84% had a best response of >10% BCR::ABL1IS to prior therapy. This landmark analysis describes PFS and OS in patients with ≤1%, >1%-≤10%, and >10% BCR::ABLIS by Months 3, 6, and 12. Disease progression was defined as the loss of complete hematologic response or major cytogenetic response, development of acute- or blast-phase CML, death, or 2 instances of white blood cell count increases (>20,000 cells/μL, ≥4 weeks apart) after the first 4 weeks of treatment. Patients with ≤1% BCR::ABL1IS at baseline were excluded from this analysis. The probabilities of PFS and OS at 24 months were calculated using the Kaplan-Meier method. The proportion of patients attaining ≤1% BCR::ABLIS by 36 months was also assessed. Results: A total of 276 patients with resistant CP-CML were included in the intention-to-treat (ITT) population: 45-mg (n=93), 30-mg (n=93), and 15-mg (n=90) starting dose cohorts. At the cutoff date of May 9, 2022, 56 (20%), 78 (28%), and 95 patients (34%) had reached ≤1% BCR::ABL1IS by Months 3, 6, and 12, respectively. Among patients remaining within each dosing cohort at 36 months, most had attained ≤1% BCR::ABLIS (57%-65%). Among all ITT patients within each dosing cohort (45 mg, n=93; 30 mg, n=93; 15 mg, n=90), the highest response rate by 36 months was observed in the 45-mg cohort (35%). Four patients with ≤1% BCR::ABL1IS at baseline were excluded from the landmark analysis. Based on this landmark analysis, regardless of starting dose, patients who attained landmark response levels of ≤1% and >1-≤10% BCR::ABL1IS in 3-12 months had substantially improved PFS outcomes at 24 months compared with patients with >10% BCR::ABL1IS (Table). In the landmark analysis population, patients who did not reach ≤10% BCR::ABL1IS within 12 months had unfavorable PFS outcomes (Table). Long-term OS outcomes in the landmark analysis population were similar across all BCR::ABL1IS levels, regardless of whether response was reached by 3, 6, or 12 months (Table). Conclusion: Ponatinib provided robust responses in the OPTIC trial population comprising patients with heavily pretreated, TKI-resistant CP-CML. In this landmark analysis, attainment of ≤10% BCR::ABL1IS with ponatinib within 12 months was associated with improved long-term PFS outcomes compared with PFS outcomes associated with remaining at >10% BCR::ABL1IS. These findings underpin the clinical benefit of achieving molecular responses with ponatinib, especially achieving ≤10% BCR::ABL IS within 12 months. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Low Pre-ChemoradiotherapyPan-Immune-Inflammation Value (PIV) Measures Predict Better Survival Outcomes in Locally Advanced Pancreatic Adenocarcinomas.

ObjectiveThis study sought to determine whether pretreatment pan-immune-inflammation value (PIV) could be used to predict prognosis in patients with locally advanced pancreatic adenocarcinoma (LA-PAC) following definitive concurrent chemoradiotherapy (C-CRT).MethodsThe outcomes of 178 LA-PAC patients who received definitive C-CRT were analyzed retrospectively. For all patients, the PIV was calculated using the peripheral blood platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) counts obtained on the first day of C-CRT: PIV=P×M×N÷L. The optimum cutoff values for PIV connected to progression-free (PFS) and overall survival (OS) results were sought using receiver operating characteristic (ROC) curve analysis. The OS and PFS differences between the PIV groups constituted the primary and secondary endpoints, respectively.ResultsROC curve analysis indicated that the ideal PIV cutoff was 464 (AUC: 75.9%, sensitivity: 74.1%, specificity: 71.9%), which categorized patients into two groups based on PFS and OS results: low PIV (L-PIV; N = 69) and high PIV (H-PIV; N = 109). According to comparative survival analyses, patients in the L-PIV group had significantly longer median PFS (14.3 vs 7.3 months; HR: 3.04; P<0.001) and OS (25.9 vs 13.3 months; HR: 2.86; P<0.001) than those in the H-PIV group. Although none of the H-PIV patients could survive beyond 5 years, the estimated 5-year OS rate was 29.7% in the L-PIV cohort. In multivariate analyses, besides the L-PIV, N0 nodal stage, and CA 19–9 ≤ 90 U/mL appeared to be the independent predictors of better PFS (P < 0.05 for each) and OS (P < 0.05 for each) results.ConclusionThe present results indicated that pre-C-CRT L-PIV measures were associated with favorable median and long-term PFS and OS results in LA-PAC patients, suggesting that the PIV is a potent and independent novel prognostic biomarker.

530P PRIMA/ENGOT-OV26/GOG-3012 study: Updated long-term PFS and safety

Niraparib (nir) has shown PFS benefit as a first-line (1L) maintenance therapy (MT) in the PRIMA primary analysis (data cut 17 May 2019) in all subgroups regardless of biomarker status. These results were the basis for approval of nir as MT after response to 1L platinum-based chemo (CT). Here we report updated long-term efficacy and safety in the PRIMA study.