scholarly journals LDH Levels Predict Progression-Free Survival in Treatment-NaÏVe Patients with Trisomy 12 Chronic Lymphocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3211-3211 ◽  
Author(s):  
Francesco Autore ◽  
Paolo Strati ◽  
Idanna Innocenti ◽  
Francesco Corrente ◽  
Livio Trentin ◽  
...  
Keyword(s):  
Research Funding ◽  
Cohort Analysis ◽  
Univariate Analysis ◽  
External Validation ◽  
Progression Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Biological Features ◽  
Treatment Naïve ◽  
Trisomy 12

Abstract Introduction. Patients with CLL and FISH positive for trisomy 12 (+12) have unique clinical and biological features. We, therefore, performed an analysis of the association between demographic, clinical, laboratoristic and biological features and outcomes in treatment-naive patients with +12 CLL. Methods. This study included 312 treatment-naive patients with +12 CLL from 9 centers. These patients, diagnosed between January 2000 and July 2016, were compared to a control group of 580 treatment-naive patients with FISH negative CLL, matched by age and gender and followed in the same centers. An additional cohort of 250 patients with +12 CLL followed at a single US institution was used as external validation. Results. Patients' baseline characteristics are shown in Table 1. As compared to patients with negative FISH, patients with +12 had a significant higher prevalence of elevated LDH (p<0.001), elevated β-2-microglobulin (p<0.001), ZAP70 positivity (p<0.001), CD38 positivity (p<0.001), CD49d positivity (p<0.001) and unmutated IGHV (p<0.001). Among patients with +12, 206 (66%) progressed and 193 (62%) required treatment, 76 (24%) patients died and 28 (9%) deaths were attributed to CLL. Among patients with negative FISH, 260 (45%) progressed and 213 (37%) were treated, 97 (17%) patients died and 46 (8%) deaths were attributed to CLL progression. Patients with +12 CLL showed shorter survival in terms of progression free survival (PFS: 69 months vs 110 months, p<0.001), treatment free survival (TFS: 77 months vs 125 months, p<0.001) and overall survival (OS: 147 months vs 165 months, p=0.005). Clinico-biological factors associated with shorter PFS were found performing univariate analysis among +12 CLL patients. These data were confirmed also when using the external validation group of +12 patients for ZAP70 positivity (p=0.03), CD38 positivity (p=0.004), β-2-microglobulin levels (p<0.001) and Rai stage (p<0.001). Furthermore we divided our cohort of patients with +12 CLL according to LDH levels available at diagnosis: 73 patients showed levels above the normal limit many times and 149 patients had normal levels. High LDH levels resulted associated with a shorter PFS (37 months vs 73 months, p<0.001; Figure 1), shorter TFS (41 months vs 84 months, p<0.001), shorter OS (115 months vs 155 months, p=0.002) and shorter CLL-specific survival (134 months vs 179 months, p<0.001). This association was maintained on multivariable analyses both for PFS (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.3 to 3.0; p=0.002) and TFS (HR 1.81, 95% CI 1.1-3.0; p=0.025). LDH levels were also significantly correlated to OS (p<0.05) evaluating the events attributed to CLL. Conclusions. In this large cohort analysis of 321 patients with +12 CLL, we were able to confirm that LDH levels above normal are common in this group and we observed that LDH levels independently predict a shorter PFS, TFS and CLL-specific survival in this population. LDH levels at diagnosis could allow to suspect trisomy 12 in CLL patients and predict different prognosis. Disclosures Coscia: Karyopharm: Research Funding; ROCHE: Honoraria, Other: Advisory board; Gilead: Honoraria; Mundipharma: Honoraria; Janssen: Honoraria. D'Arena:Janssen-Cilag: Honoraria. Reda:Gilead: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees.

The effect of prior abiraterone (Abi) treatment on subsequent response to docetaxel in men with castrate resistant prostate cancer (CRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 136-136
Author(s):  
Michael Thomas Schweizer ◽  
Xian Chong Zhou ◽  
Hao Wang ◽  
Sunakshi Bassi ◽  
Michael Anthony Carducci ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cross Resistance ◽  
Control Group ◽  
Free Survival ◽  
Subsequent Response ◽  
Risk Of Progression ◽  
Psa Response ◽  
Castrate Resistant

136 Background: Taxanes are hypothesized to mediate their effect in CRPC, at least in part, by disrupting androgen receptor trafficking along microtubules. This raises the possibility of cross-resistance between androgen-directed agents (e.g., Abi) and Tax. Methods: We retrospectively evaluated Tax efficacy in CRPC patients (N=119) who did (Abi+Tax; n=24) or did not (Tax; n=95) receive prior Abi. To ensure a contemporaneous control group, this analysis only included men who started Tax between 12/2007 (the date we began using Abi at our center) and 5/2013. Univariate and propensity score-weighted multivariable analyses for PSA progression-free survival (PSA-PFS) and all-cause progression-free survival (PFS) were conducted to evaluate the effect of prior Abi on responses to Tax. Results: Men in the Abi+Tax group had a significantly higher risk of progression than those in the Tax group. In univariate analysis, PSA-PFS was shorter in the Abi+Tax group (HR 2.00; 95%CI 1.13–3.52; P=0.016), as was PFS (HR 1.97; 95%CI 1.13–3.41; P=0.016). Median PSA-PFS was 4.1 mo in the Abi+Tax group and 6.3 mo in the Tax group (P=0.014). Median PFS was also shorter in the Abi+Tax group (4.1 vs 6.8 mo; P=0.014). In multivariable analysis, prior Abi treatment remained a predictor of shorter PSA-PFS and PFS (Table). PSA declines ≥50% were also less frequent in the Abi+Tax group (37% vs 63%, P=0.04). Conclusions: Men receiving Abi prior to Tax were more likely to develop progression on Tax (and less likely to have a PSA response) than Abi-naive patients. Cross-resistance between Abi and Tax may limit taxane efficacy in Abi-pretreated patients. [Table: see text]

scholarly journals Elevated Lactate Dehydrogenase Has Prognostic Relevance in Treatment-Naïve Patients Affected by Chronic Lymphocytic Leukemia with Trisomy 12

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 896
Author(s):  
Autore ◽  
Strati ◽  
Innocenti ◽  
Corrente ◽  
Trentin ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Chronic Lymphocytic Leukemia ◽  
Clinical Laboratory ◽  
External Validation ◽  
Variable Region ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Region Gene ◽  
Free Survival ◽  
Treatment Naïve

Chronic Lymphocytic Leukemia (CLL) patients with +12 have been reported to have specific clinical and biologic features. We performed an analysis of the association between demographic; clinical; laboratory; biologic features and outcome in CLL patients with +12 to identify parameters predictive of disease progression; time to treatment; and survival. The study included 487 treatment-naive CLL patients with +12 from 15 academic centers; diagnosed between January 2000 and July 2016; and 816 treatment-naïve patients with absence of Fluorescence In Situ Hybridization (FISH) abnormalities. A cohort of 250 patients with +12 CLL followed at a single US institution was used for external validation. In patients with +12; parameters associated with worse prognosis in the multivariate model were high Lactate DeHydrogenase (LDH) and β-2-microglobulin and unmutated immunoglobulin heavy-chain variable region gene (IGHV). CLL patients with +12 and high LDH levels showed a shorter Progression-Free-Survival (PFS) (30 months vs. 65 months; p < 0.001), Treatment-Free-Survival (TFS) (33 months vs. 69 months; p < 0.001), Overall Survival (OS) (131 months vs. 181 months; p < 0.001) and greater CLL-related mortality (29% vs. 11% at 10 years; p < 0.001) when compared with +12 CLL patients with normal LDH levels. The same differences were observed in the validation cohort. These data suggest that serum LDH levels can predict PFS; TFS; OS and CLL-specific survival in CLL patients with +12

Pomalidomide (Pom) in Relapsed and Refractory Multiple Myeloma (RRMM) - theUARK Compassionate Use Protocol,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3995-3995
Author(s):  
Saad Usmani ◽  
Sarah Waheed ◽  
Jackie Szymonifka ◽  
Susan Panozzo ◽  
Nathan M Petty ◽  
...  
Keyword(s):  
Research Funding ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Compassionate Use ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3

Abstract Abstract 3995 Background: Pom is a third generation immunomodulatory drug (IMiD) which has demonstrated safety and efficacy in RRMM with prior exposure/resistant to other IMiDs and bortezomib. This is the first report on the UARK Pom compassionate use experience in RRMM. Methods: First cycle Pom was given at 4mg orally Days 1–21 every 28 days; dexamethasone (DEX) was given to 9/23 patients at doses varying from 12 to 40 mg on schedules ranging from Days 1–4, weekly, twice a week, or three times a week. In the absence of at least PR, Pom dose was escalated to 5mg. 1patient also received bortezomib and 1 patient received bortezomib and cytoxan. Cox regression modeling was employed for univariate and multivariate analyses, whereas Kaplan-Meier curves were used for overall survival (OS) and progression free survival (PFS). Results: 23 patients with RRMM were enrolled. Baseline characteristics included age >=65yr in 43%, ISS stage >=II was seen in 78% of patients, cytogenetic abnormalities (CA) within 6 months in 80%, and GEP-defined high risk in 41% of patients. 22/23 patients (96%) had prior autologous stem cell transplant. 19/23 patients (83%) had at least 2 transplants. All 23 patients had disease progression after having received regimens containing bortezomib, thalidomide, lenalidomide, melphalan and steroids. At least 1 cycle of treatment was administered to all 23 patients enrolled, 52% of patients received >1 cycle of treatment and only 13% received =>5 cycles. 10 patients (43%) discontinued therapy primarily due to progression or death. 5/23 (22%) patients achieved PR, 57% had stable disease. A trend towards PFS benefit was observed in patients receiving cycle 2 (HR=0.30, p=0.215) on univariate analysis and multivariate analysis (HR=0.40, p=0.48) after adjusting for GEP-defined risk status (HR=2.69, p=0.16). Most common toxicities, counting all toxicities (>=grade 3) were: thrombocytopenia (70%), leukopenia (61%), anemia (43%), hypophosphatemia (35%) and hypokalemia (26%). Overall and progression- free survival at 12 months were 52% and 30%, respectively. Conclusions: Pom demonstrates anti-myeloma activity in this advanced RRM population, especially in a sub-population with GEP-defined low-risk disease. Disclosures: Barlogie: Celgene: Consultancy, Honoraria, Research Funding; IMF: Consultancy, Honoraria; MMRF: Consultancy; Millennium: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy; Novartis: Research Funding; NCI: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding.

Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 51-51
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Alexander Watson ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Real World ◽  
Retrospective Cohort ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Survival Times ◽  
Free Survival

51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p < 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.

AN INDIAN PROSPECTIVE STUDY OF DOCETAXEL THERAPY IN CRPC: CAN PRETREATMENT FACTORS PREDICT THE RESPONSE

2021 ◽  
pp. 78-81
Author(s):  
Devashish Kaushal ◽  
Rajeev Sood
Keyword(s):  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Carcinoma Prostate

Introduction: Studies on the effects of chemotherapy in Indian Castration-Resistant Prostate Cancer (CRPC) patients are very limited and world data is inconsistent. The purpose of the present study is to assess the effects of Docetaxel therapy in CRPC in Indian patients in terms of survival benet, both progression-free survival, and overall survival. This study also analyzes the effects of various factors on the survival of CRPC patients. Methodology: This is a single institutional prospective observational study. CRPC patients were treated with Docetaxel and followed till death as the primary endpoint or till the end of the study. Survivals were calculated with the Kaplan Meier method. Factors affecting survival were analyzed with univariate and multivariate analysis by log-rank t-test and Cox proportion hazard regression analysis. Result: Out of enrolled 101 patients, 78 were treated with Docetaxel. A decline in PSA (>50% reduction) was observed in 61.54%. Radiological response of regression noted in 40 % Nuclear Bone Scan and 19.23% CT/MRI by RECIST criteria. Progression-free survival and overall survival with Docetaxel (n=78) were 11.8 and 21 months respectively. Hemoglobin less than 11 gm%, Alkaline phosphatase more than 115 IU/dl, PSAmore than 14 ng/ml, Gleason score more than 7 and duration from diagnosis of carcinoma prostate to CRPC less than 24 months, the number of chemotherapy cycles less than 6 were all found to be signicantly associated with poor overall survival in univariate analysis while only Hemoglobin (P=0.0159) showed an independent association with overall survival in multivariate analysis. Conclusion: Overall and progression-free survival of CRPC patients with Docetaxel is 21 & 11.8 months respectively. Hemoglobin, Alkaline phosphatase, PSA, Gleason score, Docetaxel cycle, and duration from diagnosis of carcinoma prostate to CRPC were found to be signicantly associated with poor overall survival.

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma, primary tumors, and sites of metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16231-e16231
Author(s):  
Veronica Placencio-Hickok ◽  
Marie Lauzon ◽  
Natalie Moshayedi ◽  
Michelle Guan ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Regression Model ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
High Status ◽  
Free Survival ◽  
Pdac Tissue ◽  
Treatment Naïve

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and < 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.

scholarly journals 177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience

2021 ◽  
pp. 1167-1175
Author(s):  
Swayamjeet Satapathy ◽  
Bhagwant R. Mittal ◽  
Ashwani Sood ◽  
Apurva Sood ◽  
Rakesh Kapoor ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Octreotide Lar ◽  
Treatment Naïve ◽  
Long Acting

PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm ( P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively ( P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively ( P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

scholarly journals Rapid and Deep Hematologic Responses Are Associated with Improved Major Organ Deterioration Progression-Free Survival in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ashutosh D. Wechalekar ◽  
Giovanni Palladini ◽  
Giampaolo Merlini ◽  
Raymond L. Comenzo ◽  
Arnaud Jaccard ◽  
...  
Keyword(s):  
Research Funding ◽  
Progression Free Survival ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Free Survival ◽  
Major Organ ◽  
End Stage

Background: As immunoglobulin light chains present in AL amyloidosis are considered to be toxic to involved organs, especially the heart, rapid and deep hematologic remission with reduction of these light chains with frontline therapy may be crucial to improving long-term clinical outcomes. ANDROMEDA (NCT03201965) is the first phase 3 study in this patient population to evaluate major organ deterioration progression-free survival (MOD-PFS), a composite endpoint of time to end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); end-stage renal disease (requiring hemodialysis or renal transplant); hematologic progression per consensus guidelines1; and death. Here, we report the impact of early and deep hematologic responses on MOD-PFS. Methods: ANDROMEDA is a randomized, open-label, active-controlled phase 3 study of patients with newly diagnosed AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (VCd) ± daratumumab subcutaneous (DARA SC; DARA 1800 mg coformulated with recombinant human hyaluronidase PH20 in 15 mL). Key eligibility criteria were newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic multiple myeloma. Disease evaluations occurred every 4 weeks during Cycles 1-6. Hematologic responses were adjudicated by an Independent Review Committee. Landmark analyses for response were performed at 1 and 3 months (± 7 days). Analyses of hematologic responses and MOD-PFS were performed on the intent-to-treat analysis set. Patients without a baseline or post-baseline assessment were censored at randomization for the MOD-PFS analysis. Hazard ratios and corresponding 95% confidence intervals were estimated based on Cox proportional hazard model. Results: A total of 388 patients were randomized to DARA-VCd (n=195) or VCd alone (n=193). Baseline characteristics were well balanced between groups. The proportions of patients with heart and kidney involvement were 71% and 59%, respectively. Median follow-up was 11.4 months (range, 0.03-21.3+). For the 1- and 3-month landmark analysis, hematologic response was available for 356 and 289 patients, respectively. Hematologic response rates by treatment group at 1 and 3 months are shown in the Table. MOD-PFS was longer in patients with complete response (CR)/very good partial response (VGPR) at 1 and 3 months vs patients with lower levels of response (Figure). CR/VGPR at 1 and 3 months was associated with reduced risk of death or major organ deterioration in a multivariate analysis adjusting for baseline difference between involved and uninvolved free light chains and cardiac stage, (HR: 0.399, P=0.0006 and HR: 0.262, P=0.0003, respectively). At 1 and 3 months, cardiac and renal response rates were higher in those who achieved early and deep hematologic responses (CR and VGPR). Conclusions: CR/VGPR at 1 and 3 months was associated with a reduced risk of major organ deterioration and death in patients with newly diagnosed AL amyloidosis. These data confirm that initial therapy that achieves rapid and deep hematological responses is essential to improving long-term outcomes in AL amyloidosis. Reference 1. Comenzo RL, et al. Leukemia. 2012;26(11):2317-25 Disclosures Wechalekar: Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory; Celgene: Honoraria; Takeda: Honoraria, Other: Travel. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Comenzo:Caleum: Consultancy; Unum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Jaccard:Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding; Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Pei:Janssen: Current Employment, Current equity holder in publicly-traded company. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Kastritis:Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

scholarly journals Overexpression of the OCT-1 Gene Is a Biomarker Associated with Poor Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) - Data from a Retrospective Cohort from Latin America: Defining a Very High-Risk Clinical-Molecular Subgroup

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Gisele Rodrigues Gouveia ◽  
Suzete Cleusa Ferreira ◽  
Sheila Aparecida Coelho de Siqueira ◽  
Abrahão Elias Hallack Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
B Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Molecular Subgroup ◽  
Free Survival ◽  
Very High

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.

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