The Addition of Rituximab Eliminates the Negative Prognostic Impact of PMBCL Compared to DLBCL in Young Patients with CD20-Positive Aggressive Lymphomas Receiving a CHOP-Like Chemotherapy: Results of a Subgroup Analysis of the Mabthera International Trial Group (MInT) Study

Abstract PMBCL is considered to be a distinct entity among diffuse large B-cell lymphoma (DLBCL). The optimal therapy is still matter of debate and the impact of the addition of rituximab to conventional chemotherapy is unknown. The aim of this subgroup analysis of the MInT study was to evaluate the effect of rituximab in PMBCL in comparison to other DLBCL with mediastinal involvement (mDLBCL). Eligible for the MInT study (Lancet Oncol2006; 7: 379–91) were patients aged 18–60 years with DLBCL who had 0–1 risk factors according to age-adjusted International Prognostic Index (IPI), stage II-IV disease, or stage I disease with bulk. Patients were randomly assigned to six cycles CHOP-like chemotherapy regimens with or without rituximab. Consolidating radiotherapy (30–40 Gy) was given to sites of primary bulky disease. Results: Of 824 patients enrolled, 87 had PMBCL and 139 mDLBCL according to nationally centralized hematopathologist review. 44 patients (51%) with PMBCL and 65 patients (47%) with mDLBCL were randomized to the rituximab arm. The subsets were balanced for IPI, but patients with PMBCL were younger (median age 35 vs 43 years); showed more frequently an elevated LDH (63% vs 33%), stage I/II disease (92% vs 65%) and bulky disease (85% vs 60%); and received more often mediastinal radiotherapy (69% vs 37%) compared with mDLBCL. Rituximab increased the rates of complete remission or complete remission unconfirmed (CR/CRu) in both subsets although this was statistically significant only for PMBCL (see Table). This was mainly due to the fact that in both subsets rituximab virtually eliminated progressive disease (PD) under primary treatment, whereas without rituximab, PD tended to be more frequent in PMBCL than in mDLBCL (24% vs 11%, p=0.09). With a median observation time of 37 months (range 0–59), estimated 3-year event-free-survival (EFS) was improved by rituximab for PMBCL (78% vs 52%, p=0.012), mDLBCL (74% vs 59%, p=0.130), and all other DLBCL (n=597, 80% vs 60%, p<0.0001). Rituximab also improved progression-free-survival (PFS) of PMBCL, but not of mDLBCL (Table). This could be explained in part by the favorable outcome of mDLBCL compared to PMBCL in the chemotherapy-only arm (3-year PFS 77% vs 64%, p=0.08). In both subsets, the overall survival (OS) benefit observed with rituximab did not reach statistical significance (Table). Multivariable cox regression models (adjusting for treatment arm; IPI; etoposide use (CHOEP21); bulky disease; histology (PBMCL vs mDLBCL); and the interactions between histology and treatment arm, and histology and IPI, respectively) identified rituximab as a strong prognostic factor and a trend to an interaction between histology and treatment arm for the outcome of a patient. Conclusion: In young patients with PMBCL, rituximab added to 6 cycles of CHOP-like chemotherapy increases response rate, EFS, and PFS to the same extent as in other DLBCL, thereby eliminating the outcome disadvantage of PMBCL observed with CHOP-like chemotherapy alone. PMBCL Rituximab CR/CRu PD 3y-EFS 3y-PFS 3y-OS No 54% (38%–70%) 24% (11%–38%) 52% (35%–66%) 64% (46%–77%) 78% (61%–88%) Yes 80% (68%–92%) 3% (0%–7%) 78% (61%–88%) 88% (70%–95%) 89% (71%–96%) P-value 0.03 0.006 0.012 0.006 0.16 mDLBCL Rituximab CR/Cru PD 3y-EFS 3y-PFS 3y-OS No 67% (55%–78%) 11% (3%–18%) 59% (46%–70%) 77% (64%–86%) 89% (79%–95%) Yes 81% (71%–91%) 2% (0%–5%) 74% (60%–83%) 81% (68%–89%) 92% (79%–97%) P-value 0.1 0.07 0.13 0.71 0.47

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Prognostic significance of maximal tumor size (MTS) in young patients with good-prognosis diffuse large B-cell lymphoma (DLBCL) treated with CHOP-like chemotherapy with and without rituximab: Analysis of the MabThera International Trial Group (MInT) study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8053 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8053-8053

Author(s):

M. G. Pfreundschuh ◽

M. Hensel ◽

E. Cavallin-Stahl ◽

I. Vasova ◽

S. Kvaloey ◽

...

Keyword(s):

Prognostic Significance ◽

Young Patients ◽

B Cell Lymphoma ◽

Good Prognosis ◽

Prognostic Impact ◽

Bulky Disease ◽

Hazard Ratios ◽

Martingale Residual ◽

The Impact ◽

Two Populations

8053 Purpose: To determine the impact of MTS in young (18 to 60 years) patients with DLBCL and aaIPI=0,1. Patients and Methods: Outcome of patients treated with CHOP-like chemotherapy with (R-CHEMO) or without rituximab (CHEMO) was analyzed according to MTS. Results: A Martingale residual analysis revealed a linear negative prognostic impact of MTS on event-free (EFS) and overall (OS) survival. The hazard ratios for MTS per centimeter increase were significant for EFS (1.07; 95%-CI: 1.04–1.11; p<0.001) and OS (1.11; 95%-CI: 1.06–1.16; p<0.001). CHEMO 3-year EFS rates ranged between 78% for MTS <5cm and 41% for MTS >10cm. R-CHEMO 3-year EFS ranged from 83% (MTS <5cm) to 73% (MTS >=10cm). CHEMO 3-year OS rates decreased from 93% (MTS <5cm) to 74% (MTS >=10cm). R-CHEMO 3-year OS decreased from 98% (MTS <5cm) to 85% (MTS >=10cm). With CHEMO, any cut-off point between 5 and 10 cm separated a thus defined “non-bulky” from a “bulky” population with a 3-year EFS difference >20% (p<0.0001) and OS difference >12% (p<0.003), while with R-CHEMO only cut-off points >=10cm separated two populations with a significant EFS difference (9.1%; p=0.047), and cut-off points >=6cm discriminated two populations with a significant OS difference (7.6%-11.3%; p=0.037–0.0009). Conclusion: Due to the linear prognostic impact of MTS on outcome, cut-off points for “bulky” disease can be set rather arbitrarily between 5 and 10cm depending on clinical considerations. Rituximab reduces, but does not eliminate the negative prognostic impact of MTS in young patients with good-prognosis DLBCL. [Table: see text]

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Early Stage Diffuse Large B Cell Lymphoma (DLBCL) in the CHOP-R Era: Does Involved Field Radiation Therapy (IFRT) Impact Outcome?.

Blood ◽

10.1182/blood.v110.11.3433.3433 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3433-3433

Author(s):

Manzurul A. Sikder ◽

Sughosh Dhakal ◽

Jennifer Kelly ◽

Steven H. Bernstein ◽

Faith Young ◽

...

Keyword(s):

Early Stage ◽

B Cell Lymphoma ◽

Stage I ◽

Stage Ii ◽

Disease Stage ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

The Impact

Abstract Historically, patients (pts) with early stage DLBCL treated without consolidative IFRT more commonly relapsed in sites of initial disease. While event-free survival (EFS) was superior with IFRT after CHOP in the short-term in a large randomized trial (NEJM 339:21), prolonged follow-up demonstrated equivalent overall survival due in part to late relapses (Blood 98:724a). The optimal therapy for pts with early stage DLBCL in the rituximab-CHOP (R-CHOP) era has not been established. To determine the impact of IFRT after R-CHOP treatment on outcome of early stage DLBCL, we reviewed medical records of 67 consecutive pts with stage I and II DLBCL who were primarily treated with R-CHOP with or without IFRT between February 2001 and March 2006. Three to 8 cycles of R-CHOP were administered, and 30–45 Gy IFRT was administered for those irradiated. The Kaplan-Meier method was used for the estimates of outcome. EFS was measured from the date of diagnosis until first documented disease progression or death from any cause. Comparisons were adjusted for IPI by Cox proportional hazards regressions, and all tests were two sided. Median follow-up was 2.6 years (range 0.5–5.5). 45 (67%) of the pts were men. Median age at diagnosis was 60 years (range 20–92); 18 (27%) had ‘B’ symptoms; bulky disease (defined as mass >10cm) was present in 15 (22%); 27 (40%) had stage I and 40 (60%) had stage II disease. Stage-adjusted IPI score distribution was: IPI 0, n=6 (9%); IPI 1, n=17 (25%); IPI 2, n=24 (36%); IPI 3, n=16 (24%); IPI 4, n=4 (6%). 39 (58%) pts had extranodal disease (23% soft tissue, 21% head & neck, 56% others). As expected, since the majority of pts had more than 1 IPI risk factor, the 2-year event-free survival (EFS) was 68% (median EFS not reached). 11 (16%) pts had primary refractory disease including 3 pts who died during treatment, and they were excluded from further analysis. Of the remaining pts, 34 (61%) received IFRT, and 22 were treated with R-CHOP alone. The IPI scores of the 2 groups were balanced, but as expected, stage II disease was more common in pts who received R-CHOP alone. The EFS at 2 years for pts treated with consolidative IFRT was 87%, and with chemotherapy alone was 72%. When controlling for IPI score and the presence of bulky disease, there was a significant benefit in EFS for patients treated with R-CHOP + IFRT compared with R-CHOP alone (p=0.027). Therefore, in pts with early stage DLBCL treated with R-CHOP, we find improved outcomes with a combined modality approach including consolidative IFRT compared with chemotherapy alone as was observed in the CHOP era. Our study has inherent biases due to its retrospective nature, and limited follow-up. However, to our knowledge, this is the first study that compare R-CHOP with and without IFRT in early stage DLBCL, and therefore has important implications on future clinical trial designs.

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Intensified CHOP (ICHOP) +/− Rituximab in Primary Mediastinal Diffuse Large B Cell Lymphoma (PMBCL): The Role of Doxorubicin/Cyclophosphamide Dose-Intensity

Blood ◽

10.1182/blood.v112.11.3593.3593 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3593-3593

Author(s):

Rita Mazza ◽

Monica Demarco ◽

Michele Spina ◽

Massimo Magagnoli ◽

Luca Castagna ◽

...

Keyword(s):

Complete Remission ◽

Partial Remission ◽

Dose Intensity ◽

B Cell Lymphoma ◽

High Dose ◽

Bulky Disease ◽

Induction Failure ◽

The Impact ◽

Cyclophosphamide Dose

Abstract Background PMBCL is a clinical/biological distinct entity, sharing some characteristics with both classical DLBCL and Hodgkin’s lymphoma. MACOP B is considered the treatment of choice. Methods Starting from 1997, we treated PMBCL with an ICHOP regimen including cyclophosphamide 1750 mg/mq with MESNA uroprotection, doxorubicin 75 mg/mq, vincristine 1.4 mg/mq with 2 mg cap, and prednisone 100 mg d 1–5 of each 14-day courses, GCSF from day 7 to day 12. Rituximab (R) 375mg/mq/course was added to ICHOP (R-ICHOP) from 2002. Treatment plan included five courses of ICHOP±R. Cases with unfavourable prognosis according to age-adjusted International Prognostic Index (aaIPI2–3) were submitted to high dose chemotherapy (HDT) and peripheral stem cell rescue. Radiotherapy on involved sites was then delivered to all patients if at least partial remission (PR) was reached. Clinical response was evaluated through CT +/− Gallium scan (14 pts) up to 2002, and thorough CT + PET scan (16 pts) thereafter, according to Cheson criteria. Results: up to 2006, 30 pts were treated, with the following characteristics: M/F 10/20, median age 34 years (range 22–53), Ann Arbor stage I: 4, II –IIE:19, III: 1, IV: 6; bulky disease: 29; B symptoms: 14; aa IPI 0–1: 24, 2–3: 6; RICHOP/ICHOP 21/9. After ICHOP±R 15 patients achieved complete (CR) or unconfirmed complete remission (CRU), 14 PR, 1 stable disease. At the end of the whole program 29/30 pts reached CR and one progressed. Seven pts received HDT, six following ICHOP±R and one after II line chemotherapy for refractory disease. After a median observation time of 60 months 1 patient progressed and 1 patient relapsed, respectively. Both died of lymphoma. One patient with stage IIE IPI 0 relapsed 18 months after completion of ICHOP and RT and died after further 5 treatment lines including alloBMT. The other patient with stage II EB IPI 1, progressed shortly after R-ICHOP and RT and died five months later. Five-yr failure free survival and overall survival are 93.2 and 92.8, respectively. ICHOP±R was well tolerated, with neither toxic death or life-threatening toxicity. No patient interrupted the planned treatment because of toxicity. Hospitalization was required in seven cases due to febrile neutropenia (6), hemorrhagic cystitis (3 cases), and pneumonia (1). Five episodes of grade III–IV mucositis were observed in 4 patients. Of 147 delivered cycles, 25 were delayed (13 pts). Conclusion: in PMBCL, the results obtained with the ICHOP protocol are better than standard CHOP and comparable to MACOP-B, emphasizing the role of doxorubicin and cyclophosphamide dose-intensity. In this limited series, the impact of adding rituximab is not clear. R-ICHOP ICHOP Tot. Patients (N°) 21 9 30 * IPI 0; ^ IPI 1 IPI 0–1 16 8 24 IPI 2–3 5 1 6 Response to CT (N°) Complete Remission 10 5 15 Partial Remission 11 3 14 Induction Failure 0 1* 1* Response CT +RT+/− HDT (N°) Complete Remission 20 9 29 Partial Remission 0 0 0 Induction Failure 1 0 1 Relapse (N°) 0 1^ 1^ 5-yr FFP 95.2 88.9 93.2 5-yr OS 95.2 88.9 92.8 Median follow up (range) 52 months 104 months 60 months

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Differential Impact of Relative Dose-Intensity Reductions (DIR) in Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP21 or R-CHOP14

Blood ◽

10.1182/blood.v124.21.3073.3073 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3073-3073

Author(s):

Leyre Bento ◽

Francesc Garcia ◽

Antonia Maria Bautista-Gili ◽

Blanca Sanchez ◽

Lucia Garcia ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Selection Bias ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

Stage Iii ◽

Prognostic Impact ◽

Differential Impact ◽

Bulky Disease ◽

Time Period ◽

The Impact

Abstract Introduction: DLBCL is the more common non Hodgkin lymphoma. This is an aggressive lymphoma that is treated with a standard chemotherapy regimen: R-CHOP. In the last years attempts have been done to improve the outcome both increasing dose-density (CHOP14) or intensity (CHOEP, ACVBP, autologous stem cell transplantation) without obtaining benefit in terms of survival. This has allowed setting R-CHOP administered every 21 days (R-CHOP21) as the standard treatment for DLBCL patients. RDI is an important issue to consider when treating malignancies. Although this a well-known prognostic factor in Hodgkin lymphoma, scarce information has been published in DLBCL. Objective: The purpose of this study is further analyzing the prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14, to evaluate its differential impact when increasing dose density. Material and methods: All patients diagnosed of DLBCL from January-1999 to June-2013 at University Hospital Son Espases were retrospectively identified from Pathology Department registry to avoid selection bias. Only patients treated with R-CHOP21 or R-CHOP14 +/- radiotherapy were included (N=115). To increase the R-CHOP14 cohort we added also all patients treated with R-CHOP14 in the same time period in two additional hospitals (Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona) identified from their Pharmacy registries to avoid selection bias (N=42). Other regimes, consolidations or maintenance were excluded. Table 1 shows main characteristics of the global series (N=157). RDI represents the ratio of the amount of a drug actually administered to the amount planned for a fixed time period. RDI was calculated as previously described. Briefly, RDI of each drug was obtained followed by an average of RDI in CHOP consisting in the sume of RDI of the 3 drugs divided by 3. Main prognostic factors at diagnosis in DLBCL were obtained, including international prognostic index (IPI) factors. Evaluations were carried out following standard guidelines. Results: Overall response and complete response rates were similar in both groups:86% and 76% for R-CHOP21 and 94% and 74% for R-CHOP14(p=0.17 and p=0.85, respectively). Median follow-up for alive patients was 68 months (4-156). There were no differences between the two cohorts in terms of either OS or PFS (Figure 1). In the R-CHOP21, both a reduction higher than 15% in RDI [RR 7.41 (2.51-21.83); (p<0.001)] and an unfavorable R-IPI [RR 2.99 (1.1-8.16); (p=0.032) were independently associated with a worse OS. For PFS only a reduction higher than 15% in RDI [RR 4.41 (1.77-10.99) (p=0.001) was independently associated to worse PFS. By contrast, in the R-CHOP14 group an unfavourable NCCN-IPI [RR 8.74 (2.23-34.25); (p=0.002)] and the presence of B-symptoms [RR 5.13 (1.98-13.3); p=0.001)] was independently associated to worse OS and having a AA stage III-IV [RR 5.09 (1.14-22.62); p=0.032)] and bulky disease [RR 3.95 (1.46-10.7); p=0.007)] were independently related to worse PFS. RDI reductions did not show any significant impact in OS or PFS in patients treated with R-CHOP14 (Figure 2). Conclusions: Overall in our series there were no differences in terms of response or survival between patients treated with R-CHOP21 or R-CHOP14. A higher rate of RDI reduction was observed in the R-CHOP14 group. However, the impact of RDI reductions on response and survival was only observed in the R-CHOP21 group but not in patients treated with R-CHOP14. We can conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions. Table 1. Main clinical characteristics of the patients. R-CHOP21 group(n=74) R-CHOP14 group(n=83) P Age (median & range) 65 (25-88) 55 (15-79) 0.005 Sex (M/F) 34 (46%) / 40 (54%) 51 (61%) / 32 (39%) 0.056 ECOG PS > 1 17 (23%) 18 (22%) 0.85 Ann Arbor stage III-IV 40 (54%) 48 (58%) 0.75 B-symptoms 25 (34%) 26 (31%) 0.86 Elevated LDH 33 (46%) 40 (49%) 0.75 > 1 extranodal site 8 (11%) 19 (23%) 0.057 Bulky disease 23 (31%) 34 (41%) 0.24 R-IPI unfavorable 24 (32%) 26 (32%) 1 NCCN-IPI: - Low - Low-intermediate - High-intermediate - High 9 (13%) 27 (39%) 26 (38%) 7 (10%) 17 (21%) 35 (44%) 24 (30%) 4 (5%) 0.31 Elevated Beta-2-microglobulin 32 (49%) 31 (39%) 0.24 Radiotherapy 27 (36%) 27 (32%) 0.62 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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Frequency of MYC Overexpression and MYC-BCL2 Double Expression (DEL) in Localized Diffuse Large B-Cell Lymphoma (DLBCL) at a Large Academic Cancer Center

Blood ◽

10.1182/blood-2018-99-111902 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4223-4223

Author(s):

Stephanie Ryanne Corder ◽

Ankit Agarwal ◽

Jonathan Galeotti ◽

Xianming Tan ◽

Natalie S Grover ◽

...

Keyword(s):

Risk Factors ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Stage I ◽

Prognostic Impact ◽

Advanced Stage ◽

Large B Cell Lymphoma ◽

Significant Difference ◽

The Impact ◽

Large B Cell

Abstract Background: Genetic and functional drivers of diffuse large B-cell lymphoma (DLBCL) have increasingly been used to prognosticate and occasionally even guide treatment for patients with advanced stage DLBCL. In advanced disease, the non-germinal center (non-GC) phenotype, double hit lymphomas (DHLs), and double expression lymphomas (DELs) have poorer outcomes. However, the incidence and impact of these factors on patient outcomes in the limited stage setting is not as well described. In particular, the prevalence of MYC and BCL2 overexpression has not been previously described in the literature for early stage DLBCL. The purpose of our analysis was to determine the incidence of these high-risk factors and analyze if these have an impact on outcomes in patients with stage I-II DLBCL. Methods: We performed a single site retrospective study of patients newly diagnosed with stage I-II DLBCL as defined by the Ann-Arbor staging system. All patients were treated at our institution, between 2011 and 2017. Patients with stage III-IV disease, concomitant follicular lymphoma, primary mediastinal lymphoma, or CNS lymphomas were excluded. The stage-modified IPI was used to categorize patients into different risk categories. Cell of origin (COO) was determined by the Hans criteria. Double expression was defined as overexpression of both MYC (positive ≥50%) and BCL2 (positive ≥70%). Molecular rearrangements of MYC with either BCL2 or BCL6 were used to define DHLs. MYC overexpression, BCL2 overexpression, double (MYC and BCL2) expression, MYC rearrangement, and Ki67 were quantified. Whenever possible, original patient histologic tissue samples were examined if information was not available in the original pathology report. The study examined the impact of these clinical and pathologic factors on progression-free survival (PFS). The impact of prognostic factors was analyzed with the Wilcoxon rank-sum for continuous variables and chi-square tests for categorical variables. Results: A total of 35 patients were identified with stage I-II DLBCL. The median age was 60 years old (range 25-86). Twelve patients (34%) were female. Patient characteristics are summarized in Table 1. Fifteen patients (43%) were treated with chemotherapy alone, while 20 patients (57%) were treated with a combination of chemotherapy and radiation. There were 8 patients (23%) with MYC overexpression and 27 patients (77%) with BCL2 overexpression. Six patients (17%) had double expression. Of the 6 patients who were double expressers, 2 (33.3%) progressed after frontline therapy, while 4 of 25 non-double expressers progressed (16%), although this was not a statistically significant difference. The COO was the non-GC type in 16 patients (45.7%) by Hans criteria. There was 1 patient with MYC rearrangement, and this patient had progression at distant sites. We did not identify any DHLs. There was 1 patient with CNS relapse, but this patient did not have double expression or MYC rearrangement. There was no significant difference in PFS associated with any of our identified clinical and pathological factors. Conclusion: In this retrospective review, we identified the proportion of patients who have high risk genetic and pathologic risk factors. The prognostic impact of the COO in localized DLBCL has been described, and our data support the previously published studies showing no difference in localized DLBCL (Savage et al., Blood 2016 and Johnson et al., JCO 2012). The prognostic impact of DELs has been well described in advanced stage DLBCL; however, the prognostic impact of DELs in localized DLBCL is not well described. To our knowledge, this is the first study reporting the frequency of MYC and BCL2 overexpression in localized DLBCL. While it is difficult to compare rates across trials, the rate of patients with double expression at 17% is lower than the rate of approximately 30% described for advanced stage DLBCL (Johnson et al., JCO 2012 and Hu et al., Blood 2013). Additionally, there was not a significant difference in the risk of progression for DEL versus non-DEL, but this was limited by the small sample size. Disclosures Grover: Seattle Genetics: Consultancy. Dittus:Seattle Genetics: Consultancy.

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Absence of Prognostic Impact Associated with the Use of Statins in Patients with Follicular Lymphoma in the Rituximab Era: An Exploratory Analysis From the PRIMA Study.

Blood ◽

10.1182/blood.v120.21.2649.2649 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2649-2649

Author(s):

Emmanuel Bachy ◽

John F. Seymour ◽

Pierre Feugier ◽

Fritz Offner ◽

Dolores Caballero ◽

...

Keyword(s):

Follicular Lymphoma ◽

B Cell Lymphoma ◽

Prognostic Impact ◽

In Vitro Experiments ◽

Free Survival ◽

Rituximab Maintenance ◽

Anti Cd20 ◽

The Impact ◽

Statin Use

Abstract Abstract 2649 Background. Conflicting results have been published to date concerning the impact of statin use on the prognosis of patients with non-Hodgkin lymphoma (NHL) treated with a rituximab-containing first-line regimen. By impairing protein prenylation and possibly lipid-raft formation, statins have been shown to exert an antitumoral activity both on solid and hematological malignancies in vitro as well as in animal models. However, in vitro experiments have demonstrated an unexpected impairment of anti-CD20 antibody binding due to changes in conformational epitopes of the molecule. As a result, statins were found to decrease anti-CD20 induced complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Several groups worldwide attempted to assess the outcome of patients on statins receiving rituximab for NHL. No detrimental effect was observed across studies for patients with diffuse large B-cell lymphoma treated upfront with R-CHOP or R-CHOP-like regimen but a surprising prolonged event-free survival (EFS) was observed for patients with follicular lymphoma (FL) in one study. However, several caveats of the study precluded definitive conclusions to be drawn such as treatment heterogeneity, the enrollment of patients who did not receive rituximab, the retrospective assessment of statin use through medical charts and the consideration of EFS as the primary endpoint without specific evaluation of overall survival (OS). The impact of statin use on the prognosis of patients with FL therefore requires further investigation. Patients and methods. The randomized, open-label PRIMA study enrolled 1217 patients with de novo FL from 223 centers in 25 countries. Patients achieving at least a partial response following frontline therapy with R-CHOP, R-CVP or R-FCM were randomized between 2-years rituximab maintenance (every 8 weeks) or observation. A significant improvement of progression-free survival (PFS) was observed in the rituximab maintenance arm (HR=0.55, 95% CI=0.44–0.68, p<0.0001). All concomitant treatments at enrollment, including the use of statins, were prospectively collected. 1140 patients with complete medication data available at registration were included in this analysis. Among them, 10.4% (n=119) were on statins. Baseline demographic characteristics between patients on statins and those not on statins were compared with the use of a Chi-square test. Various endpoints such as EFS, PFS, OS, time-to-next lymphoma treatment (TTNLT) and time-to-next chemotherapy (TTNCT) were examined in univariate and multivariate analysis. All time-to-event durations were calculated from the date of randomization (6 months after the start of induction therapy). Results. As expected, the use of statins was associated to an older age at registration (P<0.001) and, as a consequence, to a higher FLIPI risk score (P<0.001). Male sex was also overrepresented among statins users, although not significant (P=0.07). Unexpectedly, LDH was more frequently above the upper normal limit (P=0.03). No other difference was observed with regards to demographic data according to statin use. No difference in overall response rate to induction regimen as well as in the quality of the response (CR/Cru versus PR versus others) was noted (P=0.53). No further difference was found at the end of the maintenance period either for patients in the observation or in the rituximab treatment arm. Of note, no imbalance was detected concerning the rate of adverse events between the 2 groups of patients as a whole (grade 1–2 versus 3–4, P=0.18) or with regards to each particular toxicity. Finally, outcome in terms of EFS, PFS (see figure above), OS, TTNLT and TTNCT were similar regardless of the use of statins (P=0.76, P=0.43, P=0.21, P=0.83 and P=0.31 respectively). Importantly, further adjustment for potential confounding factors in multivariate Cox models such as age, FLIPI score or LDH (which were imbalanced between the 2 groups) did not reveal a potential beneficial effect. Conclusion. As for other subtypes of NHL, the use of statins in patients with FL in the rituximab era appeared safe and was not associated with an inferior outcome as suggested by in vitro experiments. Disclosures: No relevant conflicts of interest to declare.

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Primary Mediastinal B Cell Lymphoma Treated with CHOP-Like Chemotherapy with or without Rituximab: 5-Year Results of the Mabthera International Trial Group (MInT) Study

Blood ◽

10.1182/blood.v120.21.1612.1612 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1612-1612 ◽

Cited By ~ 2

Author(s):

Mathias Witzens-Harig ◽

Anthony D Ho ◽

Evelyn Kuhnt ◽

Marek Trneny ◽

Michael Rieger ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

Bulky Disease ◽

Long Term Outcome ◽

Free Survival ◽

The Impact

Abstract Abstract 1612 Purpose The aim of this subgroup analysis of the MInT study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B cell lymphoma (PMBCL) in comparison to other diffuse large B-cell lymphoma (DLBCL). Extended follow-up was needed to establish long-term effects. Patients and Methods Eligible for the randomized open-label MInT study were patients aged 18–60 years with DLBCL who had 0–1 risk factors according to age-adjusted International Prognostic Index (aaIPI), stage II-IV disease, or stage I disease with bulk. Patients were randomly assigned to six cycles of CHOP-like regimens with or without rituximab. Consolidating radiotherapy was given to sites of primary bulky disease. Results Of 824 patients enrolled, 87 had PMBCL and 627 other types of DLBCL. Rituximab increased the rates of complete remission (unconfirmed) in both PMBCL (from 54% to 80%; p =.015) and DLBCL (from 72% to 87%; p<.001). In PMBCL rituximab virtually eliminated progressive disease (PD) (2.5% vs 24%; p =.006), whereas without rituximab PD was more frequent in PMBCL than in DLBCL (24% vs 10%; p =.023). With a median observation time of 62 months for PMBCL and 73 months for DLBCL, the 5-year event-free survival was improved by rituximab for PMBCL (79.1% vs 47.3%; p =.011) and for DLBCL (76.9% vs 59.7%; p <.001). Furthermore, 5-year progression-free survival was improved by rituximab for PMBCL (89.8% vs 60.1%; p=.006) and DLBCL (81.1% vs. 67.8%; p <.001). Overall survival benefit was similar for DLBCL (92.0% vs 80.9%; p <.001) and PMBCL (90.2% vs 78.3%; p =.234). Conclusion Addition of rituximab to 6 cycles of CHOP-like chemotherapy improved long-term outcome for young patients with PMBCL and aaIPI 0–1 and eliminated differences in outcome between PMBCL and DLBCL. Disclosures: No relevant conflicts of interest to declare.

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In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820986826 ◽

2021 ◽

Vol 20 ◽

pp. 153303382098682

Author(s):

Zhipeng Zhu ◽

Jiuhua Xu ◽

Xiaofang Wu ◽

Sihao Lin ◽

Lulu Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Subgroup Analysis ◽

Prognostic Value ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Clinicopathological Parameters ◽

Free Survival ◽

Cox Regression Analysis ◽

The Impact

Background: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Methods: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. Result: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. Conclusion: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

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G-8 Geriatric Screening Tool Independently Predicts Progression-Free Survival in Older Ovarian Cancer Patients Irrespective of Maximal Surgical Effort: Results of a Retrospective Cohort Study

Gerontology ◽

10.1159/000520328 ◽

2021 ◽

pp. 1-10

Author(s):

Katharina Anic ◽

Sophie Birkert ◽

Mona Wanda Schmidt ◽

Valerie Catherine Linz ◽

Anne-Sophie Heimes ◽

...

Keyword(s):

Ovarian Cancer ◽

Global Health ◽

Screening Tool ◽

Prognostic Index ◽

Progression Free Survival ◽

Assessment Tools ◽

Prognostic Impact ◽

Free Survival ◽

Geriatric Screening ◽

The Impact

Background: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). Methods: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Results: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056–3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. Conclusions: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

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