Treatment of Indolent B-Cell Nonfollicular Lymphomas: Final Results of the LL01 Randomized Trial of the Gruppo Italiano per lo Studio dei Linfomi

Purpose: To evaluate the effect of epirubicin on therapeutic response and survival in patients with indolent nonfollicular B-cell lymphomas (INFL) treated with pulsed high-dose chlorambucil. Patients and Methods: A total of 170 untreated patients with advanced/active INFL were randomly assigned to receive either eight cycles of high-dose chlorambucil (15 mg/m2/d) plus prednisone (100 mg/d) for 5 days (HD-CHL-P; arm A) or eight cycles of HD-CHL-P plus epirubicin 60 mg/m2 intravenous on day 1 (arm B). The responding patients were randomly assigned to either maintenance therapy with interferon alfa (IFNα-2a; 3 MU, three times weekly) for 12 months or observation. Results: There were 160 assessable patients (82 males, 78 females; median age, 63 years; range, 33 to 77 years); 77 patients were assigned to arm A, and 83 were assigned to arm B. Induction therapy led to 47 complete responses (CRs; 29.4%) and 68 partial responses (PRs; 42.5%), with no significant difference between the two arms (60 CR + PR in arm A [77.9%] and 55 CR + PR in arm B [66.3%]; P = .07). After a median follow-up of 38 months (range, 2 to 103 months), there was no between-group difference in overall survival (OS; P = .45), failure-free survival (P = .07), or progression-free survival (PFS; P = .5). Eighty-eight patients were randomly assigned to either IFNα-2a (n = 43) or observation (n = 45), without any difference in 3-year PFS (44% and 42%, respectively). Univariate analysis showed that OS was influenced by age, anemia, serum lactate dehydrogenase levels, and International Prognostic Index distribution; multivariate analysis identified age and anemia as having influence on OS. Conclusion: HD-CHL-P treatment outcome in INFL patients was good (50% 3-year PFS, minimal toxicity, and low costs); epirubicin did not add any advantage. One-year IFNα maintenance treatment did not prolong response duration.

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Clinicopathologic Features, Management and Outcomes of Blastoid Variant (BV) of Mantle Cell Lymphoma (MCL): A Nebraska Lymphoma Study Group (NLSG) Experience

Blood ◽

10.1182/blood.v124.21.2971.2971 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2971-2971

Author(s):

Vijaya R. Bhatt ◽

Fausto R. Loberiza ◽

James O. Armitage ◽

Timothy C. Greiner ◽

Martin Bast ◽

...

Keyword(s):

Lower Risk ◽

Univariate Analysis ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Cell Transplant ◽

Clinicopathologic Features ◽

Free Survival ◽

Response To Chemotherapy ◽

Significant Difference

Abstract Background: Prior studies have demonstrated unique clinicopathologic features of the BV of MCL including an inferior response to chemotherapy and poor long-term outcomes as compared to other MCL variants in the pre-rituximab era. A paucity of data precludes whether the use of rituximab or intensified therapy can overcome the inferior outcome associated with the BV. Methods MCL patients (n=169) treated by NLSG between 1983 and 2010 were included. Morphologic variants were classified based on published WHO criteria. We compared disease characteristics, therapy and outcomes according to MCL subtypes using the Kruskal Wallis or Chi-square tests. Univariate probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Multivariate analyses were performed using Cox proportional hazards regression to evaluate differences in outcomes of MCL subtypes while adjusting for prognostic covariates. Results The study population included 19% BV, 37% diffuse and 44% nodular subtypes. BV, diffuse and nodular subtypes differed in the median age (61 vs. 68 vs. 59, p=.002) and stage III/IV disease (81% vs. 79% vs. 93%, p=.05) at diagnosis, but did not differ in the distribution of sex, Karnofsky performance status (KPS), MCL international prognostic index (MIPI), lactate dehydrogenase (LDH) level, B-symptoms, or extranodal involvement. Patients received the following therapies: intensified therapy such as Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (Hyper-CVAD) +/- Rituximab (R) (30%), Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-R-like (24%), CHOP-like (35%) or others (11%). Approximately one-third received autologous (25%) or allogeneic (8%) SCT. There was a significant difference in the type of chemotherapy given in each group (p=.002) but not in the use of radiation therapy or proportion in each group receiving autologous/allogeneic stem cell transplant (SCT). Median follow-up across MCL subtypes was similar. Overall response rate was similar for BV, diffuse and nodular subtypes (68% vs. 65% vs. 80%, p=.44). The 5-year progression-free survival for BV vs. diffuse vs. nodular was 16% vs. 22% vs. 31%; p=.06, (Figure 1) and 5-year OS was 24% vs. 32% vs. 56% respectively; p=.005, (Figure 2). In multivariate analysis, compared to BV, diffuse subtype had similar risk of disease progression or death (hazard ratio, HR of 0.78, 95% confidence interval (CI) of 0.48-1.26) whereas nodular subtype had lower risk (HR 0.62, 95% CI 0.39-0.99). Additionally, low or intermediate MIPI, good KPS, absence of B-symptoms and undergoing SCT were associated with lower risk of progression or death. A subset univariate analysis of BV demonstrated no survivors beyond 5 years after conventional chemotherapy, whereas 33% remained alive at 10 years after intensified therapy. Conclusions BV and nodular MCL presented at a somewhat younger median age compared to diffuse MCL, and BV and diffuse MCL was more likely to present as stage I/II disease, compared to nodular MCL. The PFS and OS of BV MCL are similar to diffuse MCL but OS is worse than nodular MCL. The use of SCT may improve survival in MCL including BV variant. Figure 1. PFS of different subtypes of MCL Figure 1. PFS of different subtypes of MCL Figure 2. OS of different subtypes of MCL Figure 2. OS of different subtypes of MCL Disclosures Armitage: Ziopharm Oncology: Consultancy; GlaxoSmithKline: Consultancy; Spectrum Pharmaceuticals: Consultancy; Roche: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees.

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Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL

Blood ◽

10.1182/blood-2005-04-1603 ◽

2005 ◽

Vol 106 (10) ◽

pp. 3383-3385 ◽

Cited By ~ 55

Author(s):

Craig H. Moskowitz ◽

Andrew D. Zelenetz ◽

Tarun Kewalramani ◽

Paul Hamlin ◽

Simone Lessac-Chenen ◽

...

Keyword(s):

De Novo ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

High Dose ◽

Second Line ◽

Cell Of Origin ◽

Free Survival ◽

Significant Difference ◽

The Common

AbstractA number of prognostic factors affect outcome in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory disease and the second-line age-adjusted international prognostic index. In de novo DLBCL, the cell of orgin, as determined by expression microarray analysis or immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the cell of origin, as well as other pathologic markers of outcome, on the repeat biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide, carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they prognostic in the salvage setting. Pretreatment clinical factors were well balanced between the cohorts. There was no significant difference in response to SLT, HDT, event-free or overall survival based on the cell of origin or any of the common pathologic markers examined. The cell of origin as determined by IHC does not predict outcome in transplantation-eligible patients with relapsed or primary refractory DLBCL.

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Comparing the Outcome of Diffuse Large B-Cell Lymphoma in Very Elderly Patients (age greater than 80 years) with Elderly Patients (age between 65 to 79 years)

Blood ◽

10.1182/blood.v126.23.5072.5072 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5072-5072

Author(s):

Charalampos S. Floudas ◽

Ajay Dhakal ◽

Sunjay Neupane ◽

Pouyan Gohari ◽

Abhinav B Chandra

Keyword(s):

Elderly Patients ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Elderly Group ◽

Very Elderly ◽

Free Survival ◽

Significant Difference ◽

Ecog Ps

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most frequent NHL subtype and the risk for it increases with age. At the same time, in advanced countries, the population over 65 years old is increasing because of the continuous increase in life expectancy and as a result the incidence of DLBCL is increasing as well. Increasing age is a major determinant of therapeutic decisions since it is associated with the presence of concomitant diseases, however elderly (over 65 years old) and very elderly (>80 years old) patients are not often included in clinical trials. Consequently, the optimal management of patients in the very elderly has not been identified. We conducted a single-center retrospective study with the objective to compare the comorbidity profiles, chemotherapy offered and tolerance, as well as outcome between elderly and very elderly DLBCL patients. Method A chart review of patients diagnosed with DLBCL in our center from January 2008 to January 2014 identified 33 patients aged between 60 to 79 years (elderly group, EG) and 30 patients aged 80 or more (very elderly group, VEG). We analyzed the clinical and laboratory characteristics (gender, extranodal disease presence, International Prognostic Index (IPI) factors, ECOG performance status (PS), Charlson comorbidity index, B-symptoms, hemoglobin, serum albumin), Progression Free Survival (PFS) and Overall Survival (OS) in comparison between the two groups. Furthermore, we studied the percentage of patients that were offered chemotherapy in each group, the regimen that was offered and the completion of chemotherapy as planned. Results: Median age for the EG was 72 years and for the VEG was 84 years (80 - 93). Significant differences between EG and VEG were found in mean serum albumin concentration at diagnosis (3.48 vs. 2.77, p=0.008), ECOG PS (0.91 vs. 2.36, p=0.000), and International Prognostic Index (IPI) (1.76 vs. 2.54, p=0.023) between EG and VEG. Compared to EG, VEG patients were more likely to have comorbidities (100 vs. 81.8%, p=0.025) and extra-nodal disease (93.3% vs. 66.7%, p=0.012). Though there was no statistically significant difference in percent of patients receiving chemotherapy, greater percent of EG (60.6) received R-CHOP regimen compared to VEG (20.0, p=0.001). There was no significant difference in therapy related toxicity, but fewer patients in the VEG (60 vs. 90.5%, p=0.039) were able to complete the course of chemotherapy planned and fewer achieved CR (35.7% vs. 68.2, p=0.036). Median overall survival was 762 vs. 650 days (p=0.793) and median progression free survival was 704 vs. 331 days (p= 0.180) for EG versus VEG. Conclusion: Very elderly DLBCL patients may differ from elderly patients in ECOG PS, comorbidity profile and chemotherapy regimen. These patients were less likely to complete the course of chemotherapy and fewer achieved complete response compared to the elderly group. There were no statistically significant differences in outcomes between the two groups. Disclosures No relevant conflicts of interest to declare.

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Mid-Treatment 18-FDG-Positron Emission Tomography/Computed Tomography (PET) Does Not Impact the Outcome in Patients with Aggressive Non Hodgkin Lymphoma (NHL)

Blood ◽

10.1182/blood.v112.11.5295.5295 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5295-5295

Author(s):

Patrizia Pregno ◽

Annalisa Chiappella ◽

Marilena Bellò ◽

Giulia Benevolo ◽

Carola Boccomini ◽

...

Keyword(s):

Univariate Analysis ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Response Assessment ◽

Complete Response ◽

Course Evaluation ◽

High Dose ◽

Early Evaluation ◽

End Of Treatment

Abstract Introduction and aim of the study. PET is used in staging and restaging of aggressive NHL patients at diagnosis and at the end of treatment. Early evaluation of PET after few courses of chemotherapy was reported to predict final response, progression-free survival (PFS) and overall survival (OS) in Hodgkin’s lymphoma patients, whereas contradictory data were shown in aggressive lymphomas. The aim of our study was to evaluate mid-treatment PET (PET-2) results in aggressive NHL. Patients and methods. From April 2004 to December 2007, 42 consecutive aggressive NHL patients were referred to our Hematology Department and enrolled into the study. Clinical characteristics were as follows: 29 males and 13 females; median age of 53 years (25–73); 34 diffuse large B cell, 5 mantle cell, 2 anaplastic and 1 follicular grade III NHL; 37 stage III–IV; according to International Prognostic Index (IPI) 1 patient was at low-intermediate risk, 21 at intermediate-high and 20 at high risk. Treatment plans were: Rituximab-CHOP-like chemotherapy (R-CHOP) for 6–8 courses in 18 patients and R-CHOP for 4 courses followed by high-dose chemotherapy with autologous stem cell transplantation (HDC+ASCT) in 24 patients respectively. All pts were evaluated according to standard imaging procedures completed by PET at diagnosis and at the end of the treatment. During treatment, PET-2 scan was performed after 2 or 4 courses of R-CHOP in 24 and 18 patients respectively. Results. Complete response at the end of treatment was achieved in 33 patients and partial remission in 1; in 8 patients progression disease was detected. With a median follow-up of 22 months, 2-yr PFS and 2-yr OS rates were: 72% and 80% respectively. PET-2 was negative in 30 patients and positive in 12. Two-year PFS and 2-yr OS rates were not different between PET-2 negative and PET-2 positive patients: 71% vs 75% (p=.98) and 82% vs 74% (p=.29) respectively. Final PET scan was negative in 33 patients and positive in 9. The final PET assessment was highly predictive for 2-yr PFS: PET negative 86% vs PET positive 22% (p=.000). Also the 2-yr OS was influenced by final PET: 96% vs 26% in PET negative and PET positive patients respectively (p=.000). In univariate analysis the only parameter that influenced the outcome was the final PET; conversely, IPI, sex, histology, time of PET-2 evaluation, plan of therapy had not a statistically significative impact. Conclusions. The PET is an important imagine technique for staging and end-treatment evaluation in lymphoma disease, because it can better define CR patients. In contrast to Hodgkin disease, our data suggest that the on-course evaluation of response by PET has not predictive value of response assessment: patients, even if positive at PET-2 analysis, can achieve a continuous CR at the end of therapy. More large studies are need to determine the real impact of on-course PET as response assessment in aggressive NHL patients.

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A Novel Scoring System Based on the Level of HDL-C for Predicting the Prognosis of t-DLBCL Patients: A Single Retrospective Study

BioMed Research International ◽

10.1155/2018/2891093 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Jiadai Xu ◽

Zheng Wei ◽

Yian Zhang ◽

Chen Chen ◽

Jing Li ◽

...

Keyword(s):

B Cell ◽

Scoring System ◽

International Prognostic Index ◽

Management Strategies ◽

Prognostic Index ◽

Density Lipoprotein ◽

Progression Free Survival ◽

Risk Groups ◽

Free Survival ◽

Non Hodgkin Lymphoma

The t-DLBCL patients are generally regarded to experience a poor prognosis. However, there is little consensus to guide optimal management strategies for such patients group. The present study aimed to explore the incidence of transformation and the prognosis factors for t-DLBCL patients, thereby providing insights for clinical choices. We retrospectively investigated 46 patients with diffuse large B-cell lymphomas (DLBCL) associated with an indolent small B-cell non-Hodgkin lymphoma (iNHL) from January 2007 to June 2017 in our department. In multivariate analysis, bone marrow (BM) involvement and low level of high-density lipoprotein cholesterol (HDL-C) were considered as two negatively and independently prognostic factors for overall survival (OS) (BM: p=0.007, HR 7.475, 95%CI: 1.744-32.028; HDL-C: p=0.032, HR10.037, 95%CI: 1.226-82.162). International Prognostic Index (IPI) risk group was identified as a single independent prognostic factor of progression-free survival (PFS) (p=0.048, HR 2.895, 95%CI: 1.010-8.297). A novel prognostic scoring system named BH model (BH stands for the intertwined initials of BM situation and the level of HDL-C) was further developed to stratify these patients into two risk groups, which performed well. Combining the BH scoring model and IPI scoring system could better predict the outcomes of these patients.

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The Pre-Transplant Mantle Cell Lymphoma International Prognostic Index Predicts Overall and Progression-Free Survival Following High-Dose Therapy and Autologus Stem Cell Transplant for Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v118.21.2026.2026 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2026-2026

Author(s):

Leslie A Thompson ◽

Katherine A Guthrie ◽

Lihua Elizabeth Budde ◽

Brian G. Till ◽

Oliver W. Press ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

High Dose ◽

Performance Score ◽

Free Survival ◽

Mantle Cell ◽

Independent Association

Abstract Abstract 2026 Background: High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is frequently employed to improve outcomes in patients with mantle cell lymphoma (MCL), yet results after transplant vary widely. We and others have shown that the Mantle Cell International Prognostic Index (MIPI) measured at diagnosis can predict overall survival (OS) after HDT and ASCT (Geisler, Blood 2010; Budde JCO 2011). Unfortunately, this approach is often limited at the time of transplant by the lack of available MIPI data from the time of diagnosis. Furthermore, the MIPI at diagnosis does not take into account other disease-related data that may be present at transplant. We hypothesized that the MIPI measured immediately before initiation of HDT could be attainable and predictive of outcomes after ASCT and explored the contribution of this measure along with other clinical factors to OS and progression-free survival (PFS). Methods: Records of consecutive MCL patients undergoing HDT and ASCT at our centers were reviewed under an IRB approved minimal risk protocol. Patients undergoing planned tandem autologus-allogenic transplants were excluded. MIPI elements, simplified MIPI score, and other clinical data were collected from the period immediately prior to initiation of conditioning and evaluated for their independent association with OS and PFS. Results: Between November 1995 and May 2011 190 MCL pts meeting the above criteria underwent HDT and ASCT at our centers, of these 186 (98%) had all available pretransplant MIPI data and were included in the analysis. Pretransplant MIPI scores of 0–1, 2, 3, 4, and 5–7 were seen in 27 (15%), 61 (33%), 60 (32%), 21 (11%), and 17 (9%) patients, respectively. Other baseline pretransplant characteristics included: median age 57 years (range 35–71years), elevated LDH = 48 (26%), median WBC = 4.51/μL (range 0.7 –42.43/μL), performance score 0 = 103 (55%), median prior regimens = 2 (range 1–9), blastoid variant = 16 (8%), leukemic variant = 6 (3%), chemosensitive disease = 157 (86%), and administration of rituximab (R) within 3 months prior to transplant = 139 (75%). The 8-year estimates of OS and PFS for the entire cohort were 43% (95% CI 27 – 57%) and 31% (95% CI 16 – 48%), respectively with 3 years median follow up for survivors. The pretransplant MIPI was highly associated with OS when modeled as a continuous (p=0.008) or categorical variable (p=0.002). Survival at 2 years was 88% (95% CI 78 – 93%) for MIPI 0–2, 73% (61 – 82%) for MIPI 3 or 4, and 65% (34 – 84%) for MIPI 5 or greater (Figure). Of the MIPI elements, age (hazard ratio [HR] for death 1.5 for every 10 yrs, p=0.03) and performance score (HR 1.6 for score >1, p=0.08) had the greatest independent impact on OS. In addition, chemosensitive disease (HR 0.3, p<0.001), number of prior regimens (p<0.001), and R within 3 months prior to transplant (HR 0.6, p=0.05) were all independently associated with OS after adjusting for the pretransplant MIPI. The pretranplant MIPI score was also predictive of PFS, but less so than with OS (global and categorical p=0.02) with age providing the greatest independent association (HR for death or progression 1.3 for every 10 years, p=0.08). Again, non-MIPI factors including number of prior regimens (p<0.001), blastoid variant (HR=2.1, p=.05), chemosensitive disease (HR 0.3, p<0.001), and R within 3 months prior to transplant (HR=0.4, p=0.001) independently added to predictive ability of the MIPI for PFS. Conclusions: Our data suggest that the simplified MIPI score measured immediately prior to HDT and ASCT is a readily available and robust predictive tool for OS and PFS in MCL pts undergoing transplant. This score along with other clinical factors can be utilized to counsel patients and to compare results between various treatment options. The independent association of pretransplant R with improved outcomes supports its use in this setting. Disclosures: No relevant conflicts of interest to declare.

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Therapy with of RCHOP-14 Versus RCHOP-21 for People With Aggressive or Advanced Stage Indolent B-Cell Non-Hodgkins Lymphoma: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-103091/v1 ◽

2020 ◽

Author(s):

Yue He ◽

Wenqiang Tao ◽

Dexiang Ji ◽

Wei Lu ◽

Yu Xiong ◽

...

Keyword(s):

B Cell ◽

English Language ◽

Meta Analysis ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Advanced Stage ◽

Hodgkins Lymphoma ◽

Significant Difference ◽

Non Hodgkins Lymphoma

Abstract Background: With the advent of rituximab, RCHOP is considered the appropriate chemotherapy for aggressive or advanced stage indolent B-cell Non-Hodgkins Lymphoma(NHL). RCHOP-14 seems to achieve better outcomes than RCHOP -21 in aggressive or advanced stage indolent B-cell NHL patients in recent years.Methods: To verify the befitting chemotherapy regimens for B-cell NHL patients, we searched the electronic databases for relevant English-language literature published through January 2020. The primary outcomes were complete response(CR),progression-free survival (PFS), overall survival(OS), and Adverse events (AEs). Six eligible Phase II and III clinical randomized controlled trials (RCTs) and two high-quality observational comparative studies (OCSs)were extracted, and 5565 B-cell NHL patients involved in evaluable.Results: The analysis demonstrated no significant difference for CR rate (OR= 0.98,95%CI 0.77-1.24，P=0.85)between RCHOP-14 and RCHOP-21. Compared with RCHOP-21, the merged hazard ratio (HR) for PFS and OS was, respectively, 0.94 (95% CI: 0.84-1.06, P=0.32) and 0.91(95% CI: 0.83-1.01, P= 0.08) after treatment with RCHOP-14.A subgroup analysis based on the international prognostic index(IPI) score showed that both chemotherapy regimens were applicable in B-cell NHL patients with different prognosis. The frequency of toxic side-effects was similar between schemes.Conclusions: Therefore, the data presented suggest that the efficacy and safety of both regimens are comparable and that R-CHOP14 remains a viable plan in B-cell NHL patients who prefer a shorter therapy course.

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Genetic Variants of the NKG2C/HLA-E Receptor–Ligand Axis Are Determinants of Progression-Free Survival and Therapy Outcome in Aggressive B-Cell Lymphoma

Cancers ◽

10.3390/cancers12113429 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3429

Author(s):

Bettina Wagner ◽

Ulrich Dührsen ◽

Andreas Hüttmann ◽

Holger Nückel ◽

Rafael Tomoya Michita ◽

...

Keyword(s):

B Cell ◽

Genetic Variants ◽

Nk Cell ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Fine Tuning ◽

Free Survival ◽

The Impact

Aggressive B-cell lymphomas account for the majority of non-Hodgkin lymphomas (B-NHL). NK cells govern the responses to anti-CD20 monoclonal antibodies and have emerged as attractive targets for immunotherapy in subtypes of B-NHL. NKG2C and its cognate ligand HLA-E represent key molecules for fine-tuning of NK cell-mediated immune responses. Here, we investigated the impact of genetic variants of NKG2C and HLA-E on clinical outcomes of 441 B-NHL patients. Homozygous deletion of NKG2C (NKG2C−/−) was three-fold increased in patients compared to 192 healthy controls. Among studied patients, NKG2C−/− was more abundant in International Prognostic Index (IPI) high-risk patients compared to patients with a lower IPI (p = 0.013). Strikingly, NKG2C−/− was associated with a significantly reduced 2-year PFS (progression-free survival) (p = 0.0062) and represented an independent risk factor for 2-year PFS in multivariate analysis (p = 0.005). For HLA-E, the cognate ligand of NKG2C, the HLA-E*01:01 allele frequency was increased in B-NHL patients compared to controls (p = 0.033) and was associated with complete remission in univariate (p = 0.034) and multivariate (p = 0.018) analysis. Our data suggest that NKG2C and HLA-E genotyping is a promising tool for both defining risk groups of aggressive B-NHL and predicting response to immune therapeutic approaches.

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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 ◽

10.1182/blood-2020-142715 ◽

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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Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.658331 ◽

2021 ◽

Vol 11 ◽

Author(s):

Juan Briones ◽

Maira Khan ◽

Amanjot K. Sidhu ◽

Liying Zhang ◽

Martin Smoragiewicz ◽

...

Keyword(s):

Prostate Cancer ◽

Predictive Factors ◽

Real World ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Markers ◽

Age At Diagnosis ◽

Free Survival ◽

Significant Difference

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

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