Clinical utility of interim CT scans in patients receiving bendamustine and rituximab for first line treatment of follicular lymphoma.

e19565 Background: Interim imaging with computed tomography scanning (CT) has been performed during most clinical trials of chemoimmunotherapy in patients with follicular lymphoma (FL) receiving first line systemic therapy. Based on this, interim imaging is commonly performed, but there is little evidence of its utility in clinical practice. Methods: The objective of this study was to retrospectively review outcomes of interim CTs (iCT) in adult patients with biopsy proven FL (grade 1-3a, 3b excluded) who received first line therapy with bendamustine and rituximab (BR) at Princess Margaret Cancer Centre from January 1 2013- December 31 2018. Baseline patient characteristics at diagnosis and treatment were retrieved from a prospectively populated database, and results of interim, end of treatment and end of maintenance therapy (if applicable) imaging were assessed. Disease response was assessed using Lugano response criteria as partial response (PR), complete response (CR), stable disease (SD) or progressive disease (PD). Descriptive statistics and Kaplan Meier Survival functions with a log rank test were used to analyze the data. The study was approved by the Princess Margaret Research Ethics Board. Results: A total of 108 patients were identified: mean age at diagnosis 61 years (IQR 52.4-69.5), 83% with stage III/IV disease, 27.8% bulky ( > 10cm) and median FLIPI score 2. Median follow up was 55.9 months (6.6-100.1 months). Of them, 101 patients (93.5%) had interim imaging done between cycle 2 and cycle 5 , most commonly CT scan (n = 98, 97.0%). The majority of iCTs showed a PR (n = 81, 80.1%), with a minority showing a CR (n = 11, 10.9%) and SD (n = 2, 1.9%). Seven patients had PD noted on iCT. Four patients had a second malignancy identified on biopsy of lesions found on iCT (thymoma, poorly differentiated carcinoma, lung adenocarcinoma and spindle cell tumour), 2 of whom were symptomatic at the time of iCT. Three patients had biopsy proven transformation to diffuse large B cell lymphoma (DLBCL); 2 were symptomatic at the time of iCT and only 1 had asymptomatic PD. The 3 year progression free survival (PFS) for all patients was 87.55%. Patients with a PR on iCT had similar 3 year PFS compared to those with CR (87.25% vs 90.00%, p = .52) as well as overall survival (94.80% vs 88.89%, p = .88). Conclusions: In this cohort, iCT was not useful for identifying patients with asymptomatic early progression of FL during treatment with BR. The majority of patients receiving systemic treatment for FL have at least a PR to BR on iCT, which is not associated with inferior PFS or OS compared to those with CR. Patients with symptomatic or asymptomatic PD during treatment warrant biopsy to identify histologic transformation or other malignancies. The rate of second cancers identified on iCT will be further explored in a cohort of FL patients treated with R-CVP and R-CHOP.

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Time for an individualized approach to first-line management of follicular lymphoma

Haematologica ◽

10.3324/haematol.2021.278766 ◽

2022 ◽

Vol 107 (1) ◽

pp. 7-18 ◽

Cited By ~ 1

Author(s):

Guillaume Cartron ◽

Judith Trotman

Keyword(s):

Follicular Lymphoma ◽

B Cell Lymphoma ◽

First Line ◽

Disease Response ◽

First Line Therapy ◽

Histological Transformation ◽

Early Progression ◽

Individualized Approach ◽

Survival Expectations ◽

Indolent Disease

Follicular lymphoma is a heterogeneous B-cell lymphoma both in presentation and at progression. For most patients it is a chronic, relapsing indolent disease with overall survival expectations now potentially beyond 20 years. However, in a significant minority (~20%) who experience early progression or histological transformation after treatment, the disease no longer has an indolent behavior. This review looks at the development of prognostic indices, staging and therapies for follicular lymphoma, identifying where the data can, and cannot, guide the multidisciplinary team to determine an individualized approach to first-line therapy. A nuanced patient- and disease-specific approach is necessary to maximize disease response and survival while minimizing therapeutic toxicity.

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Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy

Blood ◽

10.1182/blood-2018-10-879643 ◽

2019 ◽

Vol 134 (4) ◽

pp. 353-362 ◽

Cited By ~ 18

Author(s):

Emanuele Zucca ◽

Stephanie Rondeau ◽

Anna Vanazzi ◽

Bjørn Østenstad ◽

Ulrich J. M. Mey ◽

...

Keyword(s):

Follicular Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Complete Response ◽

Clinical Cancer Research ◽

International Prognostic Index Score ◽

First Line Therapy ◽

Phase 2 Trial ◽

Grade 3

Abstract The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

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Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v112.11.837.837 ◽

2008 ◽

Vol 112 (11) ◽

pp. 837-837 ◽

Cited By ~ 2

Author(s):

Ariel E Marciscano ◽

Neel Gupta ◽

Zhigang Zhang ◽

Julie Teruya-Feldstein ◽

Ariela Noy

Keyword(s):

Follicular Lymphoma ◽

Lower Risk ◽

Cell Lymphoma ◽

Single Agent ◽

B Cell Lymphoma ◽

P Value ◽

First Line ◽

First Line Therapy ◽

Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

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Differences in Cell of Origin (COO) Affect Outcomes in Caucasian(C) but Not in African American(AA) Patients with Diffuse Large B-Cell Lymphoma(DLBCL)

Blood ◽

10.1182/blood.v126.23.1460.1460 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1460-1460 ◽

Cited By ~ 2

Author(s):

Uma Borate ◽

Deniz Peker ◽

James M. Foran ◽

Luciano J Costa

Keyword(s):

B Cell ◽

B Cell Lymphoma ◽

Disease Stage ◽

Rank Test ◽

Advanced Stage ◽

Cell Of Origin ◽

First Line ◽

First Line Therapy ◽

Log Rank Test ◽

Line Therapy

Abstract Introduction: DLBCL is an aggressive mature B-cell neoplasm with a low incidence in African Americans and other minority groups. The differences in outcomes based on DLBCL Cell of Origin(COO) immunophenotypic subtypes as defined by the Hans algorithm using CD10, Bcl-6, and MUM1 namely germinal center B-cell (GCB) and non-GCB have been based on predominantly Caucasian patients (pts) and their impact on outcomes in AA patients have not been well studied. Material and Methods: A retrospective review of clinicopathologic data from patients diagnosed and treated for DLBCL at UAB between 2002-2011 was conducted following IRB approval .The data collected included patient demographics (age, sex, self identified race), DLBCL subtype (GCB vs. non-GCB based on the Hans algorithm), disease stage, first line therapy regimens and patient outcomes. We analyzed group differences in both C and AA pts with GCB and non-GCB subtypes of DLBCL in all the parameters mentioned above using the chi square test for categorical variables,. In addition, OS was examined using Kaplan Meier curves and the log rank test. We performed univariate and multivariate analyses to examine the effects of variables of interest on OS. All results were considered statistically significant at α=0.05 level. Results: We included a total of 259 pts in our analysis after excluding patients with missing demographics, disease related data, primary mediastianal DLBCL, missing first line therapy data and outcomes data as well as race identified as other than C or AA. 45 patients (17.4%) of patients self identified as AA and 214 (82.6%) self identified as Caucasian. The mean age of presentation for AA pts was 52 yrs compared to 58 years for C patients (p=0.045) and 28 (62.2%) AA patients presented with advanced Stage III and IV disease compared to 89 (44.6%) of C patients (P=0.04) both being statistically significant. Based on COO characterization using immunophenotype by Hans algorithm, 27 AA pts (60%) and 145(67%) of C pts were GCB by immunophenotype(p=0.317). 95% of all patients received R-CHOP as first line therapy , 3.5% received R-CVP and the remaining received a combination of Rituximab alone, FCR or radiation therapy .On analyzing OS based on COO, AA patients did not demonstrate a significant difference in OS based on COO with both GCB and non-GCB groups having a median OS of 84 months ( p=0.74)( 95% CI 72-121 months). However, the median OS for C pts with GCB phenotype was 104 months compared to 25 months for the non-GCB phenotype and the median OS was 55 months +/-12.6 months for the C pt group as a whole( p<0.001 by log rank test )which was highly statistically significant.Multivariate analyses of different factors affecting OS showed only COO (p<0.001), age(p=0.07) and stage of DLBCL at presentation(p=0.027) to affect OS significantly.Race,Gender and IPI score did not appear to impact OS significantly. Conclusion: Our study aimed to study the impact of COO and Race on OS in DLBCL especially in AA pts where this has not been well characterized. Our results show that as expected the incidence of DLBCL is lower in AA patients compared to C pts. However, DLBCL presents at younger age and with more advanced stage in AA than in C patients. Although distribution of COO is similar in AA and C patients, our findings suggest that COO may not have the same effect on prognosis among AA pts as it does among the C pt population where we see non-GCB patients do significantly worse than their GCB counterparts. This may reflect a different disease biology in AA patients that has yet to be understood. Our study limitations include not taking into account disease relapse, second line therapy and effect of autologous bone marrow transplantation on overall survival. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

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The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers

Frontiers in Oncology ◽

10.3389/fonc.2021.792340 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hye Ryeon Kim ◽

Soomin Ahn ◽

Hyunji Jo ◽

Hongsik Kim ◽

Joohyun Hong ◽

...

Keyword(s):

Objective Response ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Complete Response ◽

First Line ◽

Her2 Positive ◽

First Line Therapy ◽

The Status ◽

Tumor Mutational Burden ◽

The Impact

BackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.MethodsWe performed next-generation sequencing (NGS), including TMB analysis, in 31 HER2-positive AGC patients with trastuzumab plus chemotherapy as first-line therapy for recurrent (n=8) or metastatic (n=23) tumors. The TruSight Oncology 500 Assay from Illumina (San Diego, CA, USA) was used to evaluate TMB.ResultsAmong 31 patients, 30 had tumors with immunohistochemistry (IHC) 3+, and one was IHC 2+ and silver in situ hybridization (SISH) positive. The median age was 57.0 years old (range, 35-76), and the majority had tumors with low TMB (87.1%, n=27/31). Only four (12.9%) had tumors with high TMB. Of these four, three achieved complete response (CR) or partial response (PR) to treatment, and the remaining patient was not evaluable for tumor response. Objective response rate (ORR) to trastuzumab plus chemotherapy showed a favorable trend in patients with high TMB (75.0%, n=3/4) compared to patients with low TMB (59.3%, n=16/27) (P=0.546). The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019)ConclusionThe status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs.

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First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.7500 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 7500-7500 ◽

Cited By ~ 14

Author(s):

Ian Flinn ◽

Richard van der Jagt ◽

Julie E. Chang ◽

Peter Wood ◽

Tim E. Hawkins ◽

...

Keyword(s):

Progression Free Survival ◽

Complete Response ◽

Rank Test ◽

First Line ◽

Open Label ◽

Free Survival ◽

Non Hodgkin Lymphoma ◽

Duration Of Response ◽

Treatment Naïve

7500 Background: BRIGHT, a phase 3, open-label, noninferiority study comparing efficacy and safety of bendamustine plus rituximab (BR) vs rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP) in treatment-naive patients (pts) with indolent non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL), showed that the complete response rate for first-line BR was statistically noninferior to R-CHOP/R-CVP ( Blood 2014). Pts were monitored for ≥5 years (yr) to assess the overall effect of BR or R-CHOP/R-CVP in a controlled clinical setting. This analysis reports the time-to-event variables of the 5-yr follow-up (FU) study. Methods: Pts with iNHL or MCL randomized to 6-8 cycles of BR or R-CHOP/R-CVP underwent complete assessments at end of treatment, then were monitored regularly. Progression-free survival (PFS), event-free survival (EFS), duration of response (DOR) and overall survival (OS) were compared using a stratified log-rank test. Results: Of 447 randomized pts, 224 received BR, 104 R-CHOP, and 119 R-CVP; 419 entered the FU. The median FU time was 65.0 and 64.1 months for BR and R-CHOP/R-CVP, respectively. The 5-yr PFS rate was 65.5% (95% CI 58.5-71.6) and 55.8% (48.4-62.5), and OS was 81.7% (75.7-86.3) and 85% (79.3-89.3) for BR and R-CHOP/R-CVP, respectively. The hazard ratio (95% CI) for PFS was 0.61 (0.45-0.85; P= .0025), EFS 0.63 (0.46-0.84; P= .0020), DOR 0.66 (0.47-0.92; P= .0134), and OS 1.15 (0.72-1.84; P= .5461) comparing BR vs R-CHOP/R-CVP. Similar results were found in iNHL [PFS 0.70 (0.49-1.01; P= .0582)] and MCL [PFS 0.40 (0.21-0.75; P= .0035)], with the strongest effect in MCL. Use of R maintenance was similar, 43% in BR and 45% in R-CHOP/R-CVP. B was included as second-line in 27 (36%) of the 75 pts requiring therapy who originally received R-CHOP/R-CVP. Comparable safety profiles with expected adverse events were observed in the FU study in BR vs R-CHOP/R-CVP. Conclusions: The long-term FU of the BRIGHT study has confirmed that PFS, EFS, and DOR were significantly better for BR, and OS was not statistically different between BR and R-CHOP/R-CVP. The safety profile was as previously reported. Clinical trial information: NCT00877006.

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Clinical Complete Remission of An Advanced Gastric Adenocarcinoma After Camrelizumab Plus Chemotherapy Followed by Camrelizumab Plus Capecitabine: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.775147 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jieheng Lin ◽

Jianying Yang ◽

Wenping Wang ◽

Xiaotong Lin ◽

Yang Cao

Keyword(s):

Gastric Adenocarcinoma ◽

Progression Free Survival ◽

Complete Response ◽

Endoscopic Biopsy ◽

First Line ◽

First Line Therapy ◽

Positron Emission ◽

Pet Ct ◽

Advanced Gastric Adenocarcinoma ◽

Enhanced Computed Tomography

We report a rare case of PDL1-negative advanced gastric adenocarcinoma that improved significantly after camrelizumab plus chemotherapy followed by camrelizumab plus capecitabine as first-line therapy. A 65-year-old woman was diagnosed with a gastric adenocarcinoma in 2017 via contrast-enhanced computed tomography (CT) and endoscopic biopsy. She stabilised after preoperative neoadjuvant chemotherapy, surgery, and postoperative adjuvant chemotherapy. In September 2019, positron emission tomography (PET)/CT re-examination suggested a peritoneal metastasis and multiple lymph node metastases. She then received six cycles of camrelizumab plus chemotherapy. PET/CT indicated that the metastatic foci had disappeared and that she had achieved a clinical complete response(CCR). She was followed-up with camrelizumab plus capecitabine (maintenance therapy). At the time of writing, her progression-free survival is more than 14 months and her quality of life is good. Thus, camrelizumab plus chemotherapy is a useful first-line treatment for HER2- and PD-L1-negative advanced gastric adenocarcinoma.

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Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma. Incidence, Risk Factors and Outcomes

Blood ◽

10.1182/blood.v126.23.3968.3968 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3968-3968

Author(s):

Sabarish Ayyappan ◽

Dhivya Prabhakar ◽

Vinita Gupta ◽

Brenda Cooper ◽

Hillard M. Lazarus ◽

...

Keyword(s):

Risk Factors ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Patient Characteristics ◽

Hematologic Malignancies ◽

P Value ◽

First Line ◽

Bulky Disease ◽

First Line Therapy ◽

Line Therapy

Abstract Venous thromboembolism (VTE) is a frequent complication of hematologic malignancies, including lymphoid malignancies. VTE results in significant morbidity and mortality in lymphoma patients. There is limited information regarding the factors affecting the risk of VTE in diffuse large B cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. We conducted a retrospective analysis to identify risk factors affecting the incidence of VTE and the effect of this complication on patient outcome. Methods: We searched the hematologic malignancies database of University Hospitals Seidman Cancer Center for patients newly diagnosed with DLBCL between 2004 and 2014. Records were reviewed for baseline demographics, evidence of known risk factors for VTE, disease characteristics, treatment history and baseline laboratory values. The univariate probability of overall survival (OS) and progression free survival (PFS) was estimated using the Kaplan-Meier method. The cumulative incidence procedure was used to estimate the incidence of VTE. To identify risk factors for VTE, univariate analysis was conducted on the potential risk factors for VTE and variables with P-value .25 were selected for analysis in the multivariate logistic regression model. Results: 204 patients diagnosed with DLBCL were included. Patient characteristics are presented in table 1. The median age at diagnosis was 66 years and 63% had advanced stage at diagnosis. After a median follow up was 27 months, 34 patients (16.6%) presented a VTE, with a 3-year cumulative incidence of 13.7% (95% CI 9.2-20.3%). The VTE was a pulmonary embolism in 12 subjects (35%) and deep venous thrombosis in 22 patients (65%). The diagnosis of VTE was done in the presence of active disease in 23 subjects (67%) and the first VTE occurred during the first line of chemotherapy in 16 patients (47% of VTE). Risk factors identified by univariate analysis (table 2) included previous history of VTE, coronary artery disease and congestive heart failure, bulky disease, and absence of a complete response. Treatment with an anthracycline - containing regimen resulted in decreased risk of VTE. In multivariate analysis, only the presence of bulky disease, progressive disease after first line therapy and treatment with anthracyclines retained statistical significance (p = 0.05, 0.05 and 0.006, respectively). After a median of 27 months of follow up 113 patients had presented progression after first line therapy and 72 had died. Overall, 3-year PFS was 58.6% (95% CI 51-66.2%), with lower PFS in patients experiencing VTE (3-year PFS: VTE 34.8%; no VTE 64.4%, p=0.002). 3-year OS for the whole cohort was 70.2% (95% CI 63.1-77.3%). Patients who presented VTE had a 3-year OS of 51.3% vs. 74.8% in patients without VTE (p=0.002). DLBCL patients present a high risk of VTE, with approximately half of all VTE events occurring early in the course of the disease. We were able to identify the presence of bulky disease at diagnosis and the absence of response to first line therapy as risk factors for developing VTE. The use of anthracycline-containing regimens was protective against VTE, likely because of the increased rates of disease response. Patients with VTE had worsened outcomes, likely a result of the presence of persistent disease, although a direct effect of VTE on long-term outcomes cannot be ruled out. Our results highlight the need for a heightened awareness of the increased risk of VTE in DLBCL patients and the need for prevention strategies. Table 1. Baseline patient characteristics Median age, years (range) 66 (20-92) Gender (%) Male Female 115 (56.3%) 89 (43.6%) Stage I II III IV 32 (15.9%) 43 (21.4%) 41 (20.4%) 85 (42.3%) R-IPI 0 1-2 3-5 18 (8.8%) 104 (51.0%) 80 (39.2%) Table 2. Risk Factors and results of univariate analysis Risk factor Odds Ratio p value Age > 65 1.179 0.661 Male gender 0.847 0.659 Prior congestive heart failure 5.69 0.009 Prior VTE 4.016 0.07 Increased creatinine 3.479 0.181 Morbid obesity 5.121 0.252 Prior malignancy 1.283 0.674 Bulky disease 2.425 0.035 Stage II vs. I III vs. I IV vs. I 3.742 1.343 1.906 0.058 0.703 0.338 Elevated LDH 1.329 0.450 Hemoglobin <10g/dl 0.902 0.236 Platelets < 150,000/mcl 1 0.108 Non - GCB molecular subtype 0.658 0.439 Positive FISH for t(8;14) 1.668 0.568 Anthracycline 0.383 0.050 Rituximab 5.454 0.265 Response PR vs. CR PD vs. CR SD vs. CR 0.843 0.986 0.850 0.863 1.013 1.550 Disclosures No relevant conflicts of interest to declare.

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Retrospective Study of the Safety and Efficacy of Anlotinib Combined With Dose-Dense Temozolomide in Patients With Recurrent Glioblastoma

Frontiers in Oncology ◽

10.3389/fonc.2021.687564 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lei She ◽

Lin Su ◽

Liangfang Shen ◽

Chao Liu

Keyword(s):

Survival Curve ◽

Progression Free Survival ◽

Response Assessment ◽

Complete Response ◽

Recurrent Glioblastoma ◽

First Line ◽

Rano Criteria ◽

First Line Therapy ◽

Line Therapy ◽

Dose Dense

PurposeThe purpose of this study was to retrospectively analyze the safety and clinical efficacy of anlotinib combined with dose-dense temozolomide (TMZ) as the first-line therapy in the treatment of recurrent glioblastoma (rGBM).Patients and MethodsWe collected the clinical data of 20 patients with rGBM. All patients received anlotinib (12 mg daily, orally for 2 weeks, discontinued for 1 week, repeated every 3 weeks) combined with dose-dense TMZ (100 mg/m2, 7 days on with 7 days off) until the disease progressed (PD) or adverse effects (AEs) above grade 4 appeared. Grade 3 AEs need to be restored to grade 2 before continuing treatment, and the daily dose of anlotinib is reduced to 10 mg. The patients were reexamined by head magnetic resonance imaging (MRI) every 1 to 3 months. The therapeutic effect was evaluated according to Response Assessment in Neuro-Oncology (RANO) criteria. The survival rate was analyzed by Kaplan-Meier survival curve analysis. The baseline of all survival index statistics was the start of anlotinib combined with dose-dense of TMZ. National Cancer Institute-Common Terminology Criteria Adverse Events version 4.0 (NCI-CTCAE 4.0) was used to evaluate AEs.ResultsTwenty cases of rGBM were evaluated according to the RANO criteria after treatment with anlotinib and dose-dense TMZ, including five cases of stable disease (SD), thirteen cases of partial response (PR), one case of complete response (CR), and one case of PD. The median follow-up time was 13.4 (95% CI, 10.5–16.3) months. The 1-year overall survival (OS) rate was 47.7%. The 6-month progression-free survival (PFS) rate was 55%. In the IDH wild type group, the median PFS and median OS were 6.1 and 11.9 months, respectively. We observed that AEs associated with treatment were tolerable. One patient stopped taking the drug because of cerebral infarction. There were no treatment-related deaths.ConclusionAnlotinib combined with dose-dense TMZ for the first-line therapy showed good efficacy in OS, PFS, ORR, and DCR in the treatment of rGBM, and the AEs were tolerant. Randomized controlled clinical trials investigating the treatment of rGBM with anlotinib are necessary.

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Efficacy and toxicities of gemcitabine and cisplatin combination chemotherapy in advanced thymoma and thymic carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20007 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20007-e20007

Author(s):

Jian Fang ◽

Yang Wang

Keyword(s):

Partial Response ◽

Combination Chemotherapy ◽

Thymic Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Gemcitabine And Cisplatin

e20007 Background: Thymoma and thymic carcinoma are rare thymic epithelial tumours. This study investigated the efficacy of first-line gemcitabine and cisplatin combination chemotherapy in advanced thymoma and thymic carcinoma Methods: Retrospective review of patients with histologically-confirmed invasive, metastatic thymoma or thymic carcinoma treated with gemcitabine plus cisplatin as a first-line therapy between August 2008 and February 2016 at the Department of Respiratory Medicine II Peking University Cancer Hospital and Institute. The objective response rate was the primary end point. Results: Forty patients, 13 with thymoma and 27 with thymic carcinoma, were identified. Nine received gemcitabine and cisplatin combined with Endostar (injectable recombinant human Endostatin); 31 received gemcitabine and cisplatin only. Of the 13 patients with thymoma, four (30.8%) achieved a partial response (PR) and nine (69.2%) had stable disease (SD); no patients had a complete response (CR) or progressive disease (PD). Among the 27 patients with thymic carcinoma, 13 (48.1%) achieved a PR, 12 (44.4%) had SD and two (7.4%) had PD; no patients had a CR. In thymic carcinoma, progression free survival (PFS) was 25 months and median survival (OS) was 41 months; in thymoma, median PFS was 29 months and median OS was 77 months. As no patients achieved a complete response, objective response was defined as partial response in this study. Conclusions: This retrospective analysis indicates gemcitabine plus cisplatin has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma, especially for patents who cannot tolerate anthracyclines. [Table: see text]

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