Median Progression-free Survival For Patients Research Articles

Real-world analysis of teclistamab in 123 RRMM patients from Germany

Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.1%). With a follow-up of 5.5 months, we observed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months. In subgroup analyses, we found significantly lower ORR and median PFS in patients with extramedullary disease (37%/2.1 months), and/or an ISS of 3 (37%/1.3 months), and ide-cel pretreated patients (33%/1.8 months). Nonetheless, the duration of response in ide-cel pretreated patients was comparable to that of anti-BCMA naive patients. Infections and grade ≥3 cytopenias were the most frequent adverse events. In summary, we found that teclistamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.

Effect of metabolic syndrome on testosterone levels in patients with metastatic prostate cancer: a real-world retrospective study.

Metabolic syndrome (MetS) has been shown to have a negative impact on prostate cancer (PCa). However, there is limited research on the effects of MetS on testosterone levels in metastatic prostate cancer (mPCa). This study aims to investigate the influence of MetS, its individual components, and composite metabolic score on the prognosis of mPCa patients, as well as the impact on testosterone levels. Additionally, it seeks to identify MetS-related risk factors that could impact the time of decline in testosterone levels among mPCa patients. A total of 212 patients with mPCa were included in the study. The study included 94 patients in the Non-MetS group and 118 patients in the combined MetS group. To analyze the relationship between MetS and testosterone levels in patients with mPCa. Additionally, the study aimed to identify independent risk factors that affect the time for testosterone levels decline through multifactor logistic regression analysis. Survival curves were plotted by the Kaplan-Meier method. Compared to the Non-MetS group, the combined MetS group had a higher proportion of patients with high tumor burden, T stage ≥ 4, and Gleason score ≥ 8 points (P < 0.05). Patients in the combined MetS group also had higher lowest testosterone values and it took longer for their testosterone to reach the lowest level (P < 0.05). The median progression-free survival (PFS) time for patients in the Non-MetS group was 21 months, while for those in the combined MetS group it was 18 months (P = 0.001). Additionally, the median overall survival (OS) time for the Non-MetS group was 62 months, whereas for the combined MetS group it was 38 months (P < 0.001). The median PFS for patients with a composite metabolic score of 0-2 points was 21 months, 3 points was 18 months, and 4-5 points was 15 months (P = 0.002). The median OS was 62 months, 42 months, and 29 months respectively (P < 0.001). MetS was found to be an independent risk factor for testosterone levels falling to the lowest value for more than 6 months. The risk of testosterone levels falling to the lowest value for more than 6 months in patients with MetS was 2.157 times higher than that of patients with Non-MetS group (P = 0.031). Patients with hyperglycemia had a significantly higher lowest values of testosterone (P = 0.015). Additionally, patients with a BMI ≥ 25 kg/m2 exhibited lower initial testosterone levels (P = 0.007). Furthermore, patients with TG ≥ 1.7 mmol/L experienced a longer time for testosterone levels to drop to the nadir (P = 0.023). The lowest value of testosterone in the group with a composite metabolic score of 3 or 4-5 was higher than that in the 0-2 group, and the time required for testosterone levels to decrease to the lowest value was also longer (P < 0.05). When monitoring testosterone levels in mPCa patients, it is important to consider the impact of MetS and its components, and make timely adjustments to individualized treatment strategies.

Administering immunotherapy after anti-vascular targeted therapy improves overall survival of patients with metastatic clear cell renal cell carcinoma.

The Food and Drug Administration of the United States has approved several drugs for treating advanced metastatic renal cell carcinoma, including anti-vascular tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Options for first-line therapy include monotherapy or combination therapy. However, selecting a suitable first-line and second-line treatments to improve overall survival remains an unresolved issue. To evaluate the overall survival (OS) and progression-free survival (PFS) of patients with metastatic clear cell renal cell carcinoma (mRCC). Patients were divided into several grouped according to the treatment sequence of TKI and anti PD-1 administration. The overall survival benefit was evaluated based on the order of administration of anti PD-1 and TKI. In this retrospective propensity-matched cohort study, we identified 135 patients with mRCC treated at the Affiliated Cancer Hospital of Shandong First Medical University from January 1, 2017, to December 31, 2022. These patients had received anti PD-1 treatment as part of their first or second line of therapy. Statistical analysis was performed from June 1, 2023, to August 1, 2023. The primary outcome measure was OS, from the date of diagnosis to death or the last follow-up. PFS was monitored during treatment. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. By comparing the complete treatment course of patients, the survival of patients in different groups was compared according to the number of immunotherapy lines. The final cohort comprised 135 patients, of whom 84 received first-line therapy with anti PD-1 (include 6 patients treated with anti PD-1 (tislelizumab, carrelizumab, toripalimab or sintilizumab) alone and 78 patients treated with anti PD-1 combined with anti-vascular TKI (axitinib, sunitinib, solfanitinib or pazopanib)). The remaining 51 patients were treated with anti PD-1 as second-line therapy following an initial regime of TKIs. Patients were initially categorized based on whether anti PD-1 were used in the first-line treatment. It was observed that the OS of patients receiving first-line targeted therapy was higher than those receiving first-line immunotherapy, with a median OS of 33 months versus 15 months. To investigate this outcome further, we refined the patient groups based on the administration sequence of anti PD-1 and TKIs in the treatment regimen. We found that the median PFS of patients with first-line treatments of TKI combined with anti PD-1 was 3.5 months, compared to 14.5 months when TKI combined with anti PD-1 followed first-line TKI (p=0.0092). The median PFS for second-line treatments was 6.5 months versus 15 months (p=0.0014). Similarly, the median OS was 16.66 months and 31.88 months, respectively (p=0.008). This study indicates that administering immunotherapy following anti-vascular therapy significantly enhances both OS and PFS compared to other sequences of therapies. This finding provides valuable insights and robust data support for clinical decision-making regarding treatment sequencing.

PD-1 inhibitors combined with chemotherapy versus chemotherapy alone: efficacy and prognostic analysis in recurrent metastatic nasopharyngeal carcinoma.

To evaluate the prognostic value of combining PD-1 inhibitors (toripalimab or karelizumab) with chemotherapy for treating recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). This study retrospectively analyzed 142 patients with R/M NPC diagnosed from January 2018 to January 2022. Patients were divided into PD-1 inhibitor combined with chemotherapy group (53 patients) and chemotherapy alone group (89 patients) according to the treatment regimen. Objective remission rate (ORR), progression-free survival (PFS), and treatment-related toxicity were evaluated in both groups. The overall response rate (P=0.006) and objective remission rate (ORR) (P=0.002) were significantly higher in the combination chemotherapy group than in the chemotherapy-alone group. The incidences of hypothyroidism (P<0.001) and reactive capillary hyperplasia (P<0.001) were significantly higher in the combination chemotherapy group than in the chemotherapy-alone group. Cox regression analysis showed that treatment regimen (P<0.001), age (P<0.001), treatment duration (P=0.002), and number of treatment lines (P=0.034) were independent prognostic factors affecting patients' PFS. The prediction model constructed based on these prognostic factors had high accuracy in predicting 1-year and 2-year PFS (AUC 0.746 and 0.760, respectively). PD-1 inhibitors in combination with chemotherapy significantly improved the ORR and median PFS of patients with R/M NPC, while maintaining a favorable safety profile. Treatment regimen, age, number of lines and cycle of therapy were important independent prognostic factors for improving PFS in patients.

INFLUENCE OF THE METABOLIC SYNDROME ON THE QUALITY AND LIFETIME OF PROSTATE CANCER PATIENTS WITH THE DEVELOPMENT OF BONE MEATSTASES

Summary. Aim: to determine the quality of life, progression-free (PFS) and overall survival (OS) of patients with localized prostate cancer (PC) with existing metabolic syndrome (MS) and the development of bone metastases (BM) after radical prostatectomy (RP). Objects and methods: а retrospective clinical study diagnosed in 35 patients with localized PC and development of BM. Patients with a moderate (Grade group 2.3) and high (Grade group 4.5) risk of disease progression are divided into subgroups based on the presence and absence of MS. Analyzed indicators of recurrence-free and overall survival; the quality of life of patients was assessed using the QLQ-C30 questionnaire. Results: among 35 study participants after RP with the development of BM – 27 (77.1%) have MS, 8 (22.9%) haven’t features of MS. MS was found in 25.9% of patients with GG 2.3 and 74.1% of GG 4.5; the absence of MS was observed in 62.5 and 37.5% of patients, respectively. The median progression-free survival of patients with РС GG 2.3 and existing MS was 13.3% lower compared to the rate of patients without MS; in patients with PС GG 4.5 – by 10.5%. They also noted a decrease in the median overall survival of patients with MS compared to the rate of patients without MS by 6.4 (GG 2.3) and by 23.9% (GG 4.5). The data of the study demonstrate a decrease in the general health status of patients before RP and at the time of development of BM with existing MS by 27.6%, without MS by 5.5%. Decrease in quality-of-life indicators was noted in the following indicators: social status, fatigue, lack of appetite and the presence of financial difficulties. Conclusion: the investigation analysis showed that presence of metabolic syndrome influence on decreasing quality of life, progression-free survival and overall survival rates in patients with prostate cancer.

Randomized phase I/II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma.

We evaluated the safety and efficacy of vascular endothelial growth factor receptor (VEGFR)-targeted peptide vaccines for the immunization of patients with unresectable hepatocellular carcinoma (HCC) who had responded to transarterial chemoembolization. Twenty-two patients were randomized 1:1 to receive VEGFR-targeted peptides or placebo. The primary end-point was the safety assessment of the immunization. The secondary end-points were evaluation of immunological responses and clinical outcomes. No severe adverse events were induced by the study agents. Among the 12 patients in the vaccine group, a VEGFR1-specific cytotoxic T lymphocyte (CTL) response was induced in eight (66.7%) patients and a VEGFR2-specific CTL response was induced in 10 (83.3%). The median progression-free survival (PFS) and overall survival (OS) rates were 4.8 and 52.0months, respectively, in the vaccine group, and 2.7 and 21.8months, respectively, in the placebo group. No statistically significant differences were found between the two groups (PFS p=0.925, OS p=0.190). When divided into two groups according to immunoreactivity, the median PFS of patients with and without a strong immune response to VEGFR1 were 7.4 and 2.7months, and that to VEGFR2 were 10.6 and 2.7months, respectively; there were significant differences according to the immune response. Immunotherapy with peptide vaccines targeting VEGFR1 and VEGFR2 was well tolerated with no serious adverse events. It also effectively induced peptide-specific CTLs in patients with unresectable HCC.

Prevalence and prognosis of PIK3CA mutations in Bulgarian patients with metastatic breast cancer receiving endocrine therapy in first-line setting.

In approximately 40% of patients with HER2-negative/HR-positive breast cancer tumors, the PIK3CA gene is mutated. Despite this, clinical outcomes vary between studies in this cohort. We aimed to ascertain the prevalence of PIK3CA mutations in patients with metastatic HR+/HER2- breast in Bulgaria, as well the evaluation and comparison of progression free survival (PFS) between wild-type (WT) and mutation-positive groups in the real-world setting. Three oncology centers in Bulgaria collected 250 tissue samples between 2016 and 2022 for this multicentric retrospective study. PIK3CA mutations were identified using Real-Time qPCR. The median follow-up period was 35 months. The mean age of the mutant cohort was 57.6 ± 11.6 years, compared to 56.5 ± 12.2 years for the WT cohort (p = .52). The percentage of patients with visceral metastasis was 58.8% (n = 147). Approximately 84.3% (n = 210) of the patients had reached postmenopause. 29.2% (n = 73) of the patients had PIK3CA mutations. The predominant mutation was present in exon 20, H1047R (46.5%). We found a significant correlation only between the presence of a mutation and the metastatic diseases at diagnosis (p = .002). As first-line therapy, 67.1% of patients received endocrine therapy (ET) plus cyclin dependent kinase (CDK4/6) inhibitor, while the remainder received ET alone. The median PFS of patients in the group with the mutation was 32 months (95%, CI: 22-40) compared to 24 months in the WT cohort ((95%, CI: 21-36) (p = .45)); HR = 0.86 (95%, CI: 0.5-1.3) (p = .46). We corroborated our conclusion using propensity matching score analysis, (36 months [95% CI: 20-40] vs. 26 months [95% CI: 21-38], [p = .69]). We found that the prevalence of PIK3CA mutations in our patients was comparable to what has been reported in other nations. Our results suggest that PIK3CA mutational status has no bearing to ET efficacy in first-line setting.

KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab

KRAS is involved in the stability and expression of PD-L1. We investigated the expression of circulating mRNA (cmRNA) of KRAS4A and KRAS4B and the possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with immunotherapy. Patients without driver mutations undergoing Pembrolizumab (P) or P plus chemotherapy (PC) were prospectively accrued for liquid biopsy analysis of KRAS4A, KRAS4B, and PD-L1 cmRNA. Both KRAS isoforms were also studied for association with PD-L1 cmRNA. Of 56 patients, 28 received P and 28 PC. Patients with high levels of both KRAS isoforms showed significantly better PFS. The median PFS for KRAS4A was 29 months (95% CI 22–29 months) and KRAS4B 24 months (95% CI 13–29 months), respectively. The median PFS of patients with low levels of both isoforms was 12 months (95% CI 6–15 months for KRAS4A and 95% CI 5–20 months for KRAS4B). High KRAS4A retained a significant positive association with PFS in the multivariate model. An exploratory analysis in treatment subgroups found a positive association between high KRAS4A and KRAS4B with PFS in patients treated with P. PD-L1 cmRNA was significantly higher in patients with high KRAS isoforms levels and this effect was pronounced for high KRAS4A carriers. KRAS4A deserves further investigation as a potential marker for defining patients who may benefit the most from immune checkpoint inhibitors therapy and improving personalized cancer immunotherapeutic strategies.

Real-World Clinical Outcomes in Patients with Relapse and Refractory Multiple Myeloma Received VTD-PACE Treatment in the Era of Monoclonal Antibody

The treatment outcomes of multiple myeloma (MM) have drastically improved with the use of novel agents, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies. However, ultimately, the disease relapses and results in a fatal outcome. Even in cases of relapse, treatment outcomes have improved with the use of novel agents. However, in situations where novel agents have been exhausted or when the disease rapidly progresses, bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) is frequently utilized, with reported effectiveness. However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE at the Japanese Red Cross Medical Center between June 2016 and April 2023. The characteristics of the 60 patients are shown in Table 1. The VTD-PACE regimen consisted of 1 mg/m 2 of bortezomib on days 1, 4, 8, and 11 administered subcutaneously; 200 mg of thalidomide administered orally on days 1-4; 40 mg of dexamethasone administered orally on days 1-4; and a 4-day continuous intravenous infusion of 10 mg/m 2 cisplatin, 40 mg/m 2 cyclophosphamide, 40 mg/m 2 etoposide, and 10 mg/m 2 doxorubicin. The cisplatin dose was adjusted based on renal function, as determined by the treating physician. The responses were evaluated according to the International Myeloma Working Group response criteria. High-risk cytogenetic abnormalities (HRCA) included del (17p), t(4;14), and t(14;16). Double-class refractory disease was defined as refractoriness to PIs and IMiDs, whereas triple-class refractory disease was defined as refractoriness to PIs, IMIDs, and anti-CD38 monoclonal antibodies. Penta-drug refractory disease was defined as refractoriness to bortezomib, carfilzomib, lenalidomide, pomalidomide, and anti-CD38 antibodies. The median follow-up period was 11.1 months (range, 0.5-72.0 months), during which they received a median of two cycles of VTD-PACE. The overall response (ORR), stringent complete response, complete response, and very good partial response rates were 66.7% (40 patients), 13.3% (8 patients), 5% (3 patients), and 20% (12 patients), respectively. The results of univariate analysis for factors associated with response rate are shown in Table 2. The ORRs in patients with ≥4 and ≤3 prior lines were 53.1% and 82.1%, respectively ( P = 0.027). Extramedullary disease (EMD), refractoriness to anti-CD38 antibody, HRCA, and triple-class/penta-drug refractory disease did not significantly reduce the ORR. The median overall survival (OS) was 17 months with a median progression-free survival (PFS) of 9.8 months. The median PFS in patients with and without receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE were 9.8 and 5.1 months, respectively ( P = 0.023). The median OS in patients with and without renal dysfunction were 10.7 months and 21.5 months, respectively ( P = 0.0091). A trend for longer OS was observed in patients with HSCT or CART following VTD-PACE (P = 0.18). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response is expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use. However, the response rate decreased in late lines; therefore, its use in early lines is recommended.

Outcomes of Triple Class Refractory Multiple Myeloma Patients: A Single Center Retrospective Study

BACKGROUND Despite recent advances in the treatment of multiple myeloma (MM), the disease remains incurable. Recent studies suggest that patients who are triple class refractory (TCR) to a proteasome inhibitor (PI), immunomodulatory agent (IMiD), and anti-CD38 monoclonal antibody (mAb) have especially poor outcomes with a median overall survival (OS) of less than 1 year. However, studies with these results have been conducted in large academic institutions. In this study, we retrospectively analyzed outcomes among MM patients with TCR MM in a single clinic specializing in the care of patients with MM. METHODS A retrospective chart review was conducted among patients with TCR MM who were treated in a single clinic specializing in the care of patients with this B-cell malignancy. From July 2003 to July 25, 2022, we determined these patients' progression-free survival (PFS), OS, cytogenetics, lines of prior therapy (LOT), and first treatment they received after they became TCR. Kaplan-Meier analysis was utilized to assess differences in PFS, OS from diagnosis, and OS from TCR status based on high-risk cytogenetics, defined as the presence of t(4;14), t(14;16), t(14;20), 1q gain, or deletion 17p, compared to those with standard-risk cytogenetics. Kaplan-Meier analysis was also used to compare PFS according to number of lines of prior LOT, time to TCR, and drug class used for the first treatment after becoming TCR. RESULTS TCR developed in 121 patients. The median time from diagnosis to development of TCR disease was 33.4 months (mo; range, 1.5-187 mo). Patients with a time to TCR status of &amp;gt; 33.4 months had a longer PFS (median 5.2 mo) compared with patients with a time to TCR status of &amp;lt; 33.4 mo (median 2.5 mo; p=0.0171). The median LOT these patients received was 7 (range, 3-26). The median LOT prior to becoming TCR was 3 (range: 2-12). The median PFS of patients from their first treatment following the development of TCR was 4.5 months; patients with &amp;lt; or &amp;gt; 3 LOT prior to becoming TCR had the same median PFS (4.5 mo). However, PFS was shorter for high-risk (median = 2.5 mo) than standard risk (median = 4.2 mo) TCR MM patients, but this did not reach statistical significance (p = 0.0633). The median OS from diagnosis of MM was 94.8 mo (range, 5.8 - 320.6 mo). Cytogenetic data was available for 65 patients (54%). Of these, 35 (54%) harbored high-risk cytogenetics. The median OS of TCR patients with high-risk cytogenetics from diagnosis was 98.2 mo and was not different from those with standard risk disease (74.2 mo; p = 0.704). Notably, the median OS of patients from the time of development of TCR was 25.5 mo (range, 1.5 - 186.8 mo); OS was shorter (median 18.7 mo) among those TCR patients with high-risk cytogenetics compared with that of standard risk (38.5 mo), but this was not significant (p = 0.1109). The first line of therapy administered following the development of TCR for the majority of patients (n= 108 [89%]) was retreatment with an IMID, PI, mAb, or a combination of agents from these drug classes. Thirteen patients (11%) were treated with a venetoclax- or alkylating agent-based combination therapy. In addition, all except 2 patients received steroids as part of their first treatment after developing TCR. The regimen with the longest PFS was the combination of a mAB and steroids (median 9.0 mo) but only 6 patients were treated with this combination. The shortest PFS was among those retreated with a PI and steroids (n = 15; median 2.4 mo). The use of an IMID with steroids was the most frequently used combination treatment (n=32) with a median PFS of 3.4 mo. CONCLUSION Despite being refractory to a PI, IMID, and mAb, TCR patients in our single-center retrospective study showed a median OS of more than 2 years (25.5 mo) from the development of TCR. This OS is the longest reported to date in this population of MM patients. Cytogenetic differences failed to predict both OS and PFS from the development of TCR. In addition, the number of prior lines of therapy did not predict PFS from their first treatment after showing TCR. The time to development of TCR, however, did predict OS as patients who took longer to become TCR had a longer median OS. The results of this study show that time to becoming TCR is a prognostic factor for this group of patients. Our study shows that OS is considerably longer for patients with TCR than has been previously reported.

The Relapse-to-Therapy Interval in Relapsed or Refractory Diffuse Large B Cell Lymphoma Is Associated with Clinical Outcomes

Introduction In newly diagnosed diffuse large B cell lymphoma (DLBCL), the diagnosis-to-treatment (DTI) interval is associated with clinical outcomes: patients who initiated therapy early after DLBCL diagnosis have significantly worse event free survival (EFS) (Maurer JM et al. J Clin Oncol 2018;36:1603-1610). In relapsed or refractory (R/R) DLBCL, the relapse-to-treatment interval (RTI) has gained more relevance with the recent approvals of several novel therapies including chimeric antigen receptor (CAR) T-cell therapies, which require several weeks of manufacturing time, and bispecific antibody therapies that require several weeks of desensitization through dose ramp-up to achieve therapeutic levels. The association between RTI and patient outcomes in R/R DLBCL has not yet been reported. Methods We conducted an IRB-approved retrospective review of r/r DLBCL patients treated with rituximab, ifosfamide, carboplatin, etoposide (R-ICE) as second line treatment at three academic medical centers between 2010-2020. Characteristics at the time of relapse, including RTI and treatment outcomes were collected from the electronic medical record. Outcomes evaluated included disease response to R-ICE, subsequent autologous stem cell transplant (ASCT) and CAR T cell therapy, progression free survival (PFS) and OS. All analyses were done using R and its packages. The optimal cutoff values for RTI were determined using maximally selected rank test from MaxStat and survminer packages. The association between RTI and clinical outcomes was evaluated using Fisher test and Wilcoxon rank-sum test. Survival was calculated using the Kaplan Meier method, comparisons done using log-rank. Results We identified 249 patients treated with second line R-ICE for r/r DLBCL with available RTI data. The median RTI was 18 days (IQR 9-31). The optimal RTI cutoffs calculated with maximally selected rank test were 7 days for PFS and 11 days for OS. An intermediate value of 10 days was chosen. At the time of relapse, age, gender, cell of origin and double expressor / double hit features were comparable among groups, but patients with an RTI of ≤ 10 days were more likely to have B symptoms, elevated lactate dehydrogenase, and intermediate or high IPI scores compared to those with longer RTI (table 1). The RTI had a strong association with patient outcomes. Patients with RTI of 10 days or less had a lower rate of complete remission (20% vs. 45%, p = 0.003). After a median follow up of 53 months (IQR 36-73), median PFS for patients with RTI ≤ 10 days was 5.1 vs. 12.7 months for patients with RTI &amp;gt; 10 days (p &amp;lt;0.001). Four-year PFS estimates were 17.3% for patients with RTI ≤ 10 days vs. 35.3% for patients with RTI &amp;gt; 10 days. Median OS was 26 months for patients with RTI 10 days vs. 85 months for patients with RTI &amp;gt; 10 days (figure 1). Among patients with RTI of ≤ 10 days, 46% went on to receive ASCT, whereas 64% of patients with RTI &amp;gt; 10days had ASCT (p = 0.048). On multivariate Cox proportional hazards analysis including RTI ≤10 days, age &amp;gt; 60 years at time of relapse, elevated LDH, and ECOG ≥ 2, the proportional hazards condition was met for both PFS and OS. Shorter RTI had a statistically significant association with PFS and OS, with hazard ratios (HR) of 1.80 (95% CI 1.27-2.56, p = 0.001) and 1.97 (95% CI 1.29-3.03, p = 0.002), respectively. Conclusions There is a strong association between RTI and the outcomes of R/R DLBCL patients treated with second line R-ICE chemotherapy. Our findings highlight the worse outcomes of patients with rapidly progressive, symptomatic R/R DLBCL and are particularly impactful in the era of CAR T-cells and novel immunotherapies, which can take many weeks to become available or effective. As with the DTI, clinical trials of DLBCL therapies should report RTI whenever possible. More effective and rapidly available treatment approaches should be designed to improve the outcomes of this high-risk patient population.

The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma

IntroductionResistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients.MethodsWe analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients’ body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis.ResultsMedian splenic volume change was 10% (ranging from − 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1–4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1–6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly.ConclusionOur findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

Clinical characteristics and treatment outcomes of HER2 mutation and HER2 fusion in 22 patients with advanced breast cancer.

The clinical characteristics and efficacy of human epidermal growth factor receptor-2 (HER-2)-directed agents against HER2 mutations and HER2 fusions in breast cancer are obscure due to their low frequency. We conducted a retrospective study in patients with advanced breast cancer harboring HER2 mutations and/or HER2 fusions between January 1, 2017 and January 1, 2021. Among a total of 22 patients, 17 HER2 mutations were detected, including L755S, S310F, R100=, V777L, R897W, T862A, 440-17C > G, H878Y, V842I, 73 + 9G > C, T278fs, E1069K, L755P, 226-11C > T, 574 + 12C>T, L114V and P128L. The majority of patients had ductal carcinoma, which mostly coexisted with HER2 amplification/overexpression. The median progression-free survival (PFS) of the 22 patients was 6.9 months (95% CI: 4.7, 9.1) in the first-line setting. The median PFS of patients who received first-line trastuzumab-based regimens was significantly longer than that of patients who received a first-line tyrosine kinase inhibitor (TKI) (10.8 months [95% CI: 2.9, 18.7] vs. 1.9 months [95% CI: 0.8, 3.0], p < 0.005). A total of 14 patients were treated with anti-HER2 antibody-drug conjugate (ADC), among whom the median treatment line of first-time of administration of anti-HER2 ADC was 4.5 (range, 1-10). Anti-HER2 ADC reached an objective response rate (ORR) of 42.9%, a disease control rate (DCR) of 85.7% and a median PFS of 7.3 months (95% CI: 4.4-10.1) from the first-time of administration. Our data demonstrated the clinical benefit of anti-HER2 treatment in Chinese breast cancer patients harboring HER2 mutation and/or HER2 fusion. The value of immunotherapy and treatment selection among individual HER2 variants needs further study.

The impact of insurance status on progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)

Abstract Background In addition to the previously studied socioeconomic factors associated with health disparities, insurance status can serve as a prognostic factor associated with overall survival in RCC patients (Zhang et al., Future Oncol 2019). Moreover, within this population, having access to health insurance has been reported to result in earlier detection of disease (Javier-DesLoges et al., JAMA Netw Open 2021). In this study, we explored the impact of primary and secondary insurance status on PFS and OS in patients receiving first line systemic therapy for mRCC. Methods Patients with mRCC from two NCI-designated comprehensive cancer centers diagnosed between 1990 and 2022 with available insurance information were retrospectively identified using institutional databases. Primary insurance information was categorized into three groups—Medicare, private insurance, and Medicaid/no insurance—while secondary insurance was defined by the presence or absence of secondary coverage. PFS and OS were estimated by Kaplan-Meier method and compared based on insurance status using log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to examine the impact of insurance status on PFS and OS. Results In total, 645 patients with mRCC had accessible information and were included in our analysis. Of these, 344 (53.3%), 250 (38.8%), and 51 (7.9%) had primary Medicare, private insurance, and Medicaid/no insurance, respectively. Overall, most patients were male (73.0%), with a median age of 60.0 (22.0-94.0) at time of diagnosis. The most commonly rendered first-line treatments were monotherapy with targeted agents (66.4%), dual immunotherapy (13.6%), and targeted/immunotherapy combinations (10.2%). Median PFS for the entire cohort was 6.6 months (95% CI, 5.9-7.7). Median PFS for patients with primary Medicare was 7.7 months (95%, CI 7.0-9.0), 5.5 months (95% CI, 4.0-7.0) for patients with private insurance, and 4.9 months (95% CI, 3.8-8.1) for Medicaid/uninsured patients. Using an overall log-rank test, a significant difference in PFS among the three groups with different primary insurance was observed (p&amp;lt;0.0001). The median PFS for patients with secondary insurance was 8.1 months (95% CI, 6.6-11.3) compared to 6.1 months (95% CI, 5.5-7.4) for patients without secondary insurance. A multivariate Cox model with adjustment for other factors (such as age, gender, and ethnicity) revealed a statistically significant difference in PFS between patients with and without secondary insurance (p=0.0281). Median OS for the entire cohort was 36.8 months (95% CI, 32.4-44.3). Median OS for patients with primary Medicare, private insurance, and Medicaid/no insurance was 49.0 months (95%, CI 41.8-55.3), 28.5 months (95% CI, 24.1-35.7), and 21.6 months (95% CI, 17.5-42.3), respectively. By an overall log-rank test, a significant difference in OS across the three groups of primary insurance was observed (p=0.0003). No statistically significant differences in OS were observed between patients with and without secondary insurance. Overall, patients with primary Medicare had superior median PFS (p=0.0327) and OS (p=0.0004) compared to those with Medicaid/no insurance; although patients with private insurance had a lower risk of progression and death compared to those with Medicaid/no insurance, the result was not statistically significant. Conclusions In this real-world study, we investigated the impact of insurance status on clinical outcomes in patients with mRCC receiving systemic therapy. mRCC patients with primary Medicaid/no insurance or private insurance had inferior median PFS and OS compared to those with primary Medicare. Moreover, patients with secondary insurance had superior PFS over those with primary insurance alone. Overall, our findings suggest that insurance status may serve as a determinant of clinical outcomes. These hypothesis-generating data warrant external validation in prospective studies.

Sustained remissions in CLL after frontline FCR treatment with very-long-term follow-up

AbstractChemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up compared with the patients in our prior report in 2015. Only 4 of 45 patients (9%) with IGHV-M progressed beyond 10 years. Excluding Richter transformation, 96 of 300 patients (32%) developed 106 other malignancies, with 19 of 300 (6.3%) developing therapy-related myeloid neoplasms (tMNs), which were fatal in 16 of 19 (84%). No pretreatment patient characteristics predicted the risk of tMNs. In summary, FCR remains an option for patients with IGHV-M chronic lymphocytic leukemia (CLL), with a significant fraction achieving functional cure of CLL. A risk-benefit assessment is warranted when counseling patients, balancing potential functional cure with the risk of late relapses and serious secondary malignancies.

Tyrosine kinase inhibitor therapy in pediatric sarcoma: Prognostic implications of pulmonary metastatic cavitation.

This study aims to ascertain the prevalence of cavitations in pulmonary metastases among pediatric and young adult patients with sarcoma undergoing tyrosine kinase inhibitor (TKI) therapy, and assess whether cavitation can predict clinical response and survival outcomes. In a single-center retrospective analysis, we examined chest computed tomography (CT) scans of 17 patients (median age 16years; age range: 4-25years) with histopathologically confirmed bone (n=10) or soft tissue (n=7) sarcoma who underwent TKI treatment for lung metastases. The interval between TKI initiation and the onset of lung nodule cavitation and tumor regrowth were assessed. The combination of all imaging studies and clinical data served as the reference standard for clinical responses. Progression-free survival (PFS) was compared between patients with cavitating and solid nodules using Kaplan-Meier survival analysis and log-rank test. Five out of 17 patients (29%) exhibited cavitation of pulmonary nodules during TKI therapy. The median time from TKI initiation to the first observed cavitation was 79days (range: 46-261days). At the time of cavitation, all patients demonstrated stable disease. When the cavities began to fill with solid tumor, 60% (3/5) of patients exhibited progression in other pulmonary nodules. The median PFS for patients with cavitated pulmonary nodules after TKI treatment (6.7months) was significantly longer compared to patients without cavitated nodules (3.8months; log-rank p-value=.03). Cavitation of metastatic pulmonary nodules in sarcoma patients undergoing TKI treatment is indicative of non-progressive disease, and significantly correlates with PFS.

Safety and efficacy of anlotinib hydrochloride capsules in advanced non-small-cell lung cancer: a multicenter, real-world study.

Objective: To investigate the safety and efficacy of anlotinib hydrochloride capsules in stage III-IV non-small-cell lung cancer (NSCLC). Methods: NSCLC patients received anlotinib monotherapy or combination therapy. The primary end point was adverse reactions during anlotinib treatment and the secondary end point was progression-free survival. Results: During anlotinib treatement, 41.85% (167/399) of patients experienced adverse reactions, and the monotherapy group had a lower incidencethan thecombination group (36.89vs 49.68%; p=0.012). The median progression-free survival of patients in the monotherapy group was significantly lower than that in the combination group (5 vs 6months; p=0.0119). Conclusion: Compared with anlotinib monotherapy, combination therapy resulted in longer PFS and a higher incidence of adverse reactions in patients with NSCLC.

Cabozantinib for Advanced Hepatocellular Carcinoma in the Latest Real-World Practice: A Multicenter Retrospective Analysis.

Cabozantinib was found to be effective as a second- or third-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 CELESTIAL trial. So far, as immunotherapy has substituted molecular target agents as the primary systemic therapy for advanced HCC, cabozantinib is extensively used in the latest real-world clinical practice in a greatly different position than that shown by the CELESTIAL trial. In the current analysis, we examined the safety and effectiveness of cabozantinib administration in real-life settings for patients with advanced HCC. We retrospectively obtained data from patients with advanced HCC who received cabozantinib in three institutions in Japan between 14 September 2018 and 30 November 2021. During the study period, 23 patients with advanced HCC received cabozantinib. Our cohort included 21.7% of patients with Child-Pugh class B, and 52.2% of patients in fourth line or later. The median progression-free survival of patients given cabozantinib was 3.7months. Regarding patients with Child-Pugh class B or administration in fourth line or later, the discontinuation rate due to adverse events in patients who initialized at 40 or 20mg was lower than those who initialized at 60mg (42.9% versus 75.0%). Patients who were able to continue treatment with cabozantinib for more than 3months were more likely to undergo dose reduction than those who did not (85.7% versus 25.0%). Cabozantinib has recently been administered to a diverse range of patients, including those who were not enrolled in the CELESTIAL trial. Deliberate dose reduction could potentially offer clinical benefits to patients with impaired liver function. Furthermore, managing adverse events by reducing the dose could play a crucial role in extending the duration of treatment with cabozantinib. The preprint version of this work is available on https://www.researchsquare.com/article/rs-2655181/v1 .

Predictive and prognostic role of early apolipoprotein A-I alteration in recurrent or metastatic nasopharyngeal carcinoma patients treated with anti-PD-1 therapy.

The primary objective of this study was to evaluate the predictive and prognostic value of serum lipids in recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients received anti-PD-1 therapy. Patients treated with anti-PD-1 therapy (monotherapy or combined with chemotherapy) from two clinical trials (CAPTAIN and CAPTAIN-1st study) were included. Serum lipids were measured at baseline and after two cycles of treatment. We examined the impact of both baseline and post-treatment lipid levels on objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Of 106 patients, 89 patients (84%) were male. The patients' median age was 49 years. An early elevated (after two cycles of treatment) cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) were significantly associated with better ORR. Moreover, early elevated CHO, LDL-C, and ApoA-I were also positively correlated with DOR and PFS. Further multivariate analysis showed that only early change in ApoA-I could independently predict PFS (HR, 2.27; 95% CI, 1.11-4.61; p = 0.034). The median PFS for patients with early elevated and reduced ApoA-I was 11.43 and 1.89 months, respectively. However, baseline lipids levels do not play a significant role in the prognosis and prediction of patients with anti-PD-1 treatment. Collectively, an early elevation in ApoA-I was correlated with better outcomes for anti-PD-1 therapy in patients with R/M NPC, suggesting that clinicians should consider the early alteration of ApoA-I as a useful marker in treating R/M NPC patients with anti-PD-1.

Camrelizumab as a novel third or post-third-line treatment strategy in small cell lung cancer: a retrospective study of 12 patients.

Small cell lung cancer (SCLC) constitutes 15% of all lung cancer cases, with a comparatively low survival rate. The advent of immune checkpoint inhibitors (ICIs) has provided new alternatives for treating SCLC. However, the effectiveness of camrelizumab in the treatment of SCLC remains unclear. This retrospective case series was designed to investigate the efficacy and safety of camrelizumab in SCLC patients. The study enrolled SCLC patients recorded as having received more than one cycle of camrelizumab in the electronic medical record system. Data related to clinical and survival times were collected and statistically analyzed. From August 2019 to December 2021, the study enrolled 12 SCLC patients. The objective response rate was 41.7% (95% confidence interval [CI]: 15.2%-72.3%). The disease control rate was 83.3% (95% CI: 51.6%-97.9%). The median progression-free survival (PFS) for all patients was 4.0 months. Notably, the median PFS of patients in third- or post-third-line subgroups was 7 months (95% CI: 1.12-12.88 months). The median overall survival (OS) for all eligible patients was 10.0 months (95% CI: 7.35-12.65 months), with a 1-year survival rate of 25%. Notably, the OS of patients treated with third- or post-third-line therapy was 5-34 months, with a 1-year survival rate of 75%. The two most prevalent non-hematological adverse events associated with the immune response were pneumonitis (44.4%) and reactive cutaneous capillary endothelial proliferation (44.4%). One patient experienced an exacerbation of preexisting diabetes and reached grade 3 hyperglycemia. There were no grade 4/5 immune-related adverse events. This case series highlights the potential benefits and safety concerns of camrelizumab in SCLC patients. These findings suggest a possible strategy for third- and post-third-line treatments of SCLC. However, the conclusion is limited due to the study's retrospective nature and small sample size. Therefore, large-scale randomized controlled studies are needed to determine its efficacy.