High Incidence of Antiphospholipid Antibodies in Newly Diagnosed Patients With Lymphoma and a Proposed aPL Predictive Score

Given that the presence of antiphospholipid (aPL) antibodies has been proposed to be associated with thrombosis in newly diagnosed patients with lymphoma, we conducted a prospective cohort study on these patients. In all, 154 patients were enrolled. More than half were advanced-stage diffuse large B-cell lymphoma. Approximately one-third (35.7%) of the patients had the presence of aPLs, with single-, double-, and triple-aPL positivities of 29.9%, 5.2%, and 0.6%, respectively. Of the 154 patients, 8 (5.19%) developed symptomatic thrombosis during follow-up. There were no significant differences in the incidences of thrombosis for the aPL-positive and aPL-negative groups (5.5% vs 5.1%; P = 1.000). In a multivariate analysis, patients with male sex and lymphoma stage IV were significant risk factors for aPL positivity, with odds ratio [OR] = 2.22 (95% CI: 1.11-4.45), P = .025, and OR: 2.34 (95% CI: 1.17-4.67), P = .016, respectively. An aPL predictive score of ≥−1 was predictive of aPL positivity, with a sensitivity of 83.6% and specificity of 34.3%.

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Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients Treated with Immunochemotherapy Who Are Alive and Progression Free 12 Months After Diagnosis Have a Subsequent Overall Survival Similar to That of the General Population

Blood ◽

10.1182/blood.v120.21.1540.1540 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1540-1540 ◽

Cited By ~ 1

Author(s):

Matthew J Maurer ◽

Herve Ghesquieres ◽

Thomas E. Witzig ◽

Carrie A. Thompson ◽

Ivana N. Micallef ◽

...

Keyword(s):

Clinical Trial ◽

Overall Survival ◽

General Population ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Age And Sex

Abstract Abstract 1540 Background: Diffuse Large B-cell Lymphoma (DLBCL) is the most common lymphoma in the western world. Outcomes have improved with the standard initial therapy of rituximab and anthracyline based chemotherapy (immunochemotherapy). However, 20–40% of patients will either fail to achieve remission or relapse following initial immunochemotherapy. Most relapses occur early, and long-term outcome of relapsed/refractory patients is generally poor despite salvage regimens and stem cell transplant. Traditionally, studies for DLBCL have been evaluated using progression-free and/or overall survival. However, the event rate in DLBCL slows significantly approximately 12–18 months after diagnosis, and late events are often due to competing (non-DLBCL related) risks, especially in older patients. Here we examine outcome of DLBCL patients based on their event status at 12 months. Methods: Newly diagnosed DLBCL patients were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER). Clinical data were abstracted from medical records using a standard protocol. Patients were actively followed for events (progression, re-treatment, or death due to any cause) and overall survival (OS). Event-free status at 12 months after diagnosis (EFS12) was assessed as a dichotomous variable. Cause of death was determined by medical record and death certificate review using prospectively determined definitions. Expected survival was based on age and sex matched survival using the Minnesota population death rates. Confirmation cohorts were from a Lyon, France hospital based registry and NCCTG clinical trial N0489. Results: 680 patients with newly diagnosed DLBCL and treated with rituximab + anthracycline based chemotherapy were enrolled in the MER from 2002 to 2009. The median age was 62 years (range 18–92). 53% were male. At a median follow-up of 59 months (range 8–116), 266 patients (39%) had an event and 188 patients (28%) died. 162 patients (24%) had an event in the first 12 months after diagnosis, comprising 60% of all events. Patients with an event in the first 12 months had poor survival with death almost exclusively due to disease (Figures 1a, 2a). In contrast, patients who were event-free at 12 months had comparable survival to the age and sex matched general population (Figure 2b) and were more likely to die of other causes than DLBCL (Figure 1b). Overall survival rates by EFS12 status were validated in patients from a French hospital-based registry (N=265) and the NCCTG N0489 clinical trial (N=87) with additional replication studies underway. Conclusions: DLBCL patients who are event-free at 12 months after diagnosis have an excellent prognosis with an overall survival similar to that of an age- and sex- matched general population and are more likely to die of other causes than DLBCL. This finding has implications for clinical management, new clinical trials, and follow-up testing in this patient population. In contrast, patients with an event within the first 12 months after diagnosis have a poor prognosis with almost all deaths secondary to DLBCL. EFS status at 12 months identifies patients with poor outcomes due to disease. This can be utilized as an endpoint in biologic studies and clinical trials to address early treatment failures. EFS status at 12 months should be incorporated into prognostic models to identify high risk patients in newly diagnosed DLBCL. Disclosures: No relevant conflicts of interest to declare.

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Lymphocyte Count Persistence and Early Recovery Predicts Superior Survival and Is Independent of the International Prognostic Index in Patients Treated with CHOP Chemotherapy for Diffuse Large B Cell Lymphoma.

Blood ◽

10.1182/blood.v104.11.3252.3252 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3252-3252 ◽

Cited By ~ 2

Author(s):

Luis F. Porrata ◽

Kay M. Ristow ◽

Svetomir N. Markovic ◽

Daniel Persky ◽

Thomas M. Habermann

Keyword(s):

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Chop Chemotherapy ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract The peripheral blood absolute lymphocyte count (ALC) post-autologous stem cell transplantation is an independent predictor for survival in non-Hodgkin’s lymphoma. The role of ALC recovery during and after standard CHOP chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL) has not been reported. We hypothesized that ALC recovery during/after CHOP chemotherapy has a direct impact on survival. 135 consecutive newly diagnosed patients with DLBCL treated with CHOP from 1994 through 2000 were retrospectively analyzed. The primary end point was to assess the role of ALC recovery during and after CHOP on progression-free survival (PFS) and overall survival (OS). The ALC recovery before each of the 6 cycles and at 3 months follow-up after completion of therapy were analyzed. Of the 135 patients, 41 patients received concomitant radiation therapy. The median age was 64 years (range: 21–83) and median follow-up was 46 months (range: 1–124). Superior OS and PFS were identified in patients achieving the ALC cut-off value that discriminated clinical outcomes at a high level of significance for blood counts obtained before cycles 1 (ALC ≥ 1.5 x 109/L, OS = not reached vs 54 months, p< 0.0048; PFS = not reached vs 23 months, p <0.0005), 2 (ALC ≥1.5 x 109/L, OS = not reached vs 59 months, p <0.0255; PFS = not reached vs 30 months, p <0.0082), 3(ALC ≥1.2 x 109/L, OS = not reached vs 59 months, p<0.0074; not reached vs 30 months, p <0.0060), and at 3 months (ALC ≥ 1.2 x 109/L, OS = not reached vs 60 months, p< 0.0080; PFS = not reached vs 42 months, p < 0.0017). Similar cut-off points for cycles 4 through 6 could not be identified. The ALC recovery between each cycles 1–3 and at 3 months were not independent of each other. Multivariate analysis demonstrated ALC for cycles 1–3 and at 3 months post CHOP to be independent prognostic factor for OS and PFS when compared to other significant prognostic factors including International Prognostic Index and radiation therapy. Patients were stratified into three groups based on whether or not they achieved cut-off values of ALC in the first 3 cycles: group I= ALC achieved in at least 2 of 3 cycles; group II= ALC achieved in only 1/3 cycles; and group III= ALC cut-off not achieved. A trend towards worse OS (p< 0.0035) (Figure 1) and PFS (p< 0.0003) was identified if patients did not achieve any of the cut-off values of ALC in the first 3 cycles. These data further support the hypothesis that there is a critical role of lymphocyte (immune) recovery during and after CHOP chemotherapy in DLBCL.

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Rituximab-CHOP Versus CHOP Alone in Patients with Diffuse Large B Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.4708.4708 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4708-4708

Author(s):

Mustafa Cetiner ◽

Taflan Salepci ◽

Elif Birtas Atesoglu ◽

Mahmut Gumus ◽

Aslihan Guven ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Chop Chemotherapy ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell ◽

Chop Therapy

Abstract Recently, the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen plus rituximab (R-CHOP) have been used widely to treat patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) and it has also been reported to improve the outcome of DLBCL. We represent a retrospective analysis of newly diagnosed DLBCL patients between the years of 2003–2005 to evaluate the impact of R-CHOP therapy on response rates. Patients with DLBCL between 20–80 years of age (median: 46.0 and mean 56.2 ± 14.92) received 6 cycles of R-CHOP (n=28). For comparison, DLBCL patients between 15–76 years of age (median: 60.5 and mean 47.3 ± 16.6) who received 6 courses of CHOP therapy (n=30) were used as the control group. All patients received classical CHOP (cyclophosphamide 750 mg/m m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m m2 on day 1 and prednisone 40 mg/m m2 for 5 days) every 4 weeks. In R-CHOP group, rituximab 375 mg/m m2 was administered one day before CHOP chemotherapy. The median follow-up for R-CHOP and CHOP groups were 15.66 ± 5.90 (7–29) and 21.79 ± 9.20 (8–46) months, respectively. The International Prognostic Index (IPI) scores were not significantly different between these groups (median IPI of R-CHOP: 2.0 and mean IPI 2.01.27 ± 1.16 versus median IPI of CHOP: 1.0 and mean IPI 1.88 ± 1.26). Complete response (CR) and complete undetermined response (CuR) rate for R-CHOP was 92% (26 of 28 patients) which was statistically significantly higher than CHOP (24 of 30 patients, 80%) (p=0.004). Partial response (PR) rates for R-CHOP and CHOP groups were 7% (2 of 28 patients) and 10% (3 of 30 patients), respectively. While there were no unresponsive patients in the R-CHOP group, refractory disease rate was 10% (3 of 30 patients) in the CHOP group. Relapse rates during the follow up period were 13% (4 of 30 patients) for CHOP and 4% (1 of 28 patients) for R-CHOP group (p<.0001). No long-term toxicity appeared to be associated with the addition of rituximab to the CHOP combination. These results also confirmed the benefit of the addition of rituximab to standard CHOP chemotherapy in DLBCL even in young patients with low IPI scores.

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The Immunohistochemical Profile and Other Prognostic Factors In Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Blood ◽

10.1182/blood.v116.21.4126.4126 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4126-4126

Author(s):

Jorge J Castillo ◽

Brady Beltran ◽

Joo-Seop Chung ◽

Ivana Ilic ◽

Sirpa Leppa ◽

...

Keyword(s):

Prognostic Factors ◽

Cell Lymphoma ◽

Clinical Stage ◽

B Cell Lymphoma ◽

Complete Response ◽

Stage Iii ◽

Newly Diagnosed ◽

Overall Response ◽

Large B Cell Lymphoma ◽

Male Sex

Abstract Abstract 4126 Introduction: The immunohistochemical (IHC) profile as described by Hans and colleagues has emerged as a potential prognostic and predictive factor in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy. However, its role has not been completely elucidated. The main objective of this patient-level meta-analysis was to evaluate the IHC profile as a prognostic and predictive indicator in newly diagnosed DLBCL patients treated with R-CHOP. Secondary objectives were to identify potential novel prognostic factors in these patients. Methods: Patient-level clinical data was requested from 13 research groups that published studies on the role of the IHC profile in prognosis for DLBCL patients treated exclusively with R-CHOP. Six groups (46%) submitted their data, accounting for a total of 701 patients. The requested clinical data included age, sex, performance status, LDH levels, number of extranodal sites, clinical stage, expression of CD10, BCL-6 and MUM1, IHC profile, type of response, outcome and overall survival (OS). Logistical regression analyses were used to identify independent variables associated with overall and complete response rates. Univariate survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional-hazard regression test. P-values of <0.05 were considered statistically significant. Results: The median age was 63 years (range 16–90 years), 54% were men, 59% were 60 years or older, 24% had an ECOG ≥2, 55% had elevated LDH levels, 15% had ≥2 extranodal sites involved, 52% had stage III/IV and 48% had a non-germinal center (NGC) IHC profile. The overall response rate was 92% with complete responses seen in 78% and partial responses in 14%. The median follow-up was 34 months. In the logistical regression analysis, age ≥70, high LDH, ECOG ≥2, stage III/IV and a NGC profile were associated with improved overall response, and MUM1 expression, ECOG ≥2 and stage III/IV were associated with improved complete response. In the survival analysis, the estimated 5-year OS was 66% and the median OS was not reached. Age ≥60 years, elevated LDH levels and NGC IHC profile (Figure) were not associated with worse OS. In the multivariate analysis, age ≥70 years, male sex, ECOG ≥2 and clinical stage III/IV were independent prognostic factors for OS. A prognostic score was formulated using these 4 prognostic factors and then compared against the IPI and R-IPI scores. This novel score and the IPI score were the only independent factors for OS with HR 1.4 (95% CI 1.19–1.64) and 1.38 (95% CI 1.15–1.67) with p<0.0001 and p=0.0006, respectively. Conclusion: The IHC profile is not a prognostic indicator for OS, and it is predictive of overall response but not complete response in newly diagnosed patients with DLBCL treated with R-CHOP. Age ≥70, male sex, ECOG ≥2 and stage III/IV were independent prognostic factors for OS. A score consisting of these 4 factors showed a significant prognostic value in DLBCL patients treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Importance of Comorbidity in a Population-Based Analysis of Patients with Advanced-Stage Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP

Blood ◽

10.1182/blood.v120.21.3656.3656 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3656-3656

Author(s):

André Wieringa ◽

Eric N. van Roon ◽

Peter Joosten ◽

Tim Beerden ◽

Huib Storm ◽

...

Keyword(s):

Overall Survival ◽

Cell Lymphoma ◽

Significant Risk ◽

B Cell Lymphoma ◽

Population Based ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Ann Arbor ◽

Population Based Registry ◽

Large B Cell

Abstract Abstract 3656 Introduction Diffuse large B-cell lymphoma (DLBCL) is predominantly diagnosed in the elderly and its incidence is therefore rapidly increasing. Rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is the standard treatment for patients with newly diagnosed DLBCL. This is mainly based on data from carefully controlled randomised trials with strict eligibility criteria. Therefore data reflecting the “real world” in the rituximab era are sparse. We conducted an observational prospective cohort study to identify whether comorbidity is an independent risk factor for overall survival (OS) in patients with newly diagnosed DLBCL treated with R-CHOP with curative intent. Methods All patients with newly diagnosed DLBCL in Friesland, a Dutch province, are prospectively registered by their clinicians in a population-based registry (HemoBase®) since January 2005. Patients ≥18 years, CD20 positive, Ann Arbor stage II-IV were included if they received ≥ one cycle of R-CHOP. Clinical variables registered were age, gender, performance status (PS), Ann Arbor stage, presence of B-symptoms, lactate dehydrogenase, bulky disease, number of extranodal sites involved. Comorbidity was scored using the Charlson Comorbidity Index (CCI) [Charlson et. al.; J Chron Dis, 1987]. The score is a summation of the number of comorbidities existing at the time of diagnosis. The group was divided in low CCI (0–1) and high CCI (≥2). The primary endpoint was OS, defined as start of diagnose of DLBCL until death by any cause. Cox Proportional hazards model was used to identify significant risk factors. Variables used to calculate International Prognostic Index (IPI) and CCI were entered into the model. Kaplan-Meier curves were evaluated by log-rank test. Results Over a period of 7 years 302 patients were newly diagnosed with DLBCL after the start of the HemoBase® registry. Of those patients, 76 received no R-CHOP therapy, 9 had unknown Ann Arbor stage and 61 had Ann Arbor stage I. Therefore data from 156 patients could be retrieved from the population-based registry for further analysis. The median age was 69 years (range 23 – 93). The median observation period for the total population was 24 months (range 0 – 83) and for patients still alive 33 months (range 2 – 83). Twenty-five percent of patients had a PS≥2, 39% had IPI≥3. The percentage of patients with 8, 7, 6, 5, 4, 3, 2, or 1 R-CHOP cycle(s) given were 49, 3, 32, 1, 3, 4, 2, 6 respectively. R-CHOP21 was given to 74% and R-CHOP14 to 26%. Dose reduction of 20% or more in doxorubicin, cyclophosphamide or vincristine occurred in 26, 19, and 36% of the patients respectively. In 54% of the patients dose reduction occurred in one or more antineoplastic drugs. Twenty-five patients had a CCI≥2. Most frequently observed comorbidities in the CCI≥2 group were diabetes (36%), peripheral vascular disease (32%), chronic pulmonary disease or second tumor (28%), myocardial infarction (24%), congestive heart failure or cerebrovascular disease (16%). The percentage of patients with a CCI score of 2, 3, 4 or 5 were 64, 28, 4 and 4% respectively. In the CCI≥2 group only 16% of the patients had also a PS≥2. Three year OS in the total study population was 68%: in patients with CCI<2 71% and in CCI≥2 48%. As shown in figure 1, the median overall survival was 18 months in the CCI≥2 group and over 80 months in CCI<2 (p=0.01). From multivariate analysis of CCI and IPI variables only CCI≥2 (p=0.01; HR 2.41 (95%CI 1.20 – 4.87) and PS≥2 (p<0.001; HR 3.77 (95%CI 1.91 – 7.45) were identified as significant risk factors for poor overall survival. Conclusion In this population-based analysis of all patients with advanced-stage DLBCL treated with R-CHOP in a Dutch cohort over a period of 7 years, comorbidity is an important and independent adverse risk factor. Comorbidity data provide important prognostic information on OS, thereby aiding patient consultation in daily practice. Furthermore, our results demonstrate the importance of population-based research. Disclosures: No relevant conflicts of interest to declare.

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[18f]PET-CT Scan Is Highly Accurate in Identifying Marrow Involvement of Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v128.22.2355.2355 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2355-2355

Author(s):

Prakash Vishnu ◽

Andrew Wingerson ◽

Marie Lee ◽

Margaret Mandelson ◽

David M Aboulafia

Keyword(s):

Ct Scan ◽

De Novo ◽

Cell Lymphoma ◽

Stage Iv ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Pet Ct ◽

Pet Ct Scan ◽

Large B Cell

Abstract BACKGROUND: Recent advances in imaging and the use of prognostic indices and molecular profiling have improved our ability to characterize disease and predict outcomes in diffuse large B cell lymphoma (DLBCL). About 1/3rd of patients with DLBCL have bone marrow involvement (BMI) at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered the gold standard to detect such involvement. [18F] fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET-CT), has become a standard pre-treatment imaging in DLBCL and may be a noninvasive alternative to BMAB to ascertain BMI. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly diagnosed DLBCL, but owing to a variety of reasons this is not yet a standard of practice. The aim of this retrospective study which included 99 patients with newly diagnosed de-novo DLBCL, who had undergone both BMAB and PET-CT, was to determine the accuracy of PET-CT in detecting BMI in DLBCL and define overall survival (OS) in these patients based on BMI by BMAB vs. PET-CT. METHODS: This study is a single institution retrospective review of patients' medical records. All patients with newly diagnosed DLBCL at Virginia Mason Medical Center between January 2004 to December 2013 who underwent pretreatment PET-CT and BMAB were included. PET-CT images were visually assessed for BMI including the posterior iliac crest. Patients with primary mediastinal DLBCL, previous history or co-existence of another lymphoma subtype and those with a non-diagnostic BMAB, and in whom the PET-CT did not show marrow signal abnormality were excluded from the analysis. Ann Arbor stage was determined using PET-CT with and without the contribution of BMAB, and the proportion of stage IV cases by each method was measured. RESULTS: 99 eligible patients were identified. The median age was 62 years (range, 24-88), 62 (59%) were male, 53 (50%) had elevated LDH and 17 (16%) had an ECOG performance status of >2. Thirteen (12%) patients had > 1 extra-nodal site of lymphoma involvement. R-IPI score was 1 in 39 (37%), 2 in 42 (40%), 3 in 20 (19%), and 4 in 4 (4%) patients. A total of 38 (36%) patients had BMI established by either PET-CT (n=24, 19%), BMAB (n=14, 13%), or both (n=12, 11%). 12 of the 24 patients (50%) with positive PET-CT had BMI by DLBCL, while only 2 of the 81 patients (2%) with negative PET-CT showed BMI. BMAB upstaged 1 of the 53 (2%) stage I/II patients to stage IV. The sensitivity of PET-CT scan to detect BMI by DLBCL was 86% while the specificity was 87%. 84 patients (85%) had concordant results between lymphomatous BMAB and PET-CT (12 patients were positive for both, and 72 patients were negative for both), but 15 patients (15%) had a discordant interpretation (3 patients were positive by BMAB and negative by PET-CT, and 12 patients were negative by BMAB and positive by PET-CT). PET-CT was highly accurate for detecting BMI at diagnosis in de-novo DLBCL. Although patients with positive BMAB patients had inferior 5 year OS estimates compared to negative BMAB (66% vs. 85%), no difference was demonstrated between PET-CT positive vs. PET- CT negative patients. (79% vs. 83%) (Table 1) CONCLUSIONS: In patients with newly diagnosed DLBCL, PET-CT is highly accurate in detecting BMI by lymphoma. In clinical practice, routine BMAB may no longer be necessary for all patients with DLBCL, who are staged by PET-CT, unless the results would change both staging and therapy. The prognostic implication of BMI identified by PET-CT compared to BMAB remains unknown. Whether a PET-CT precludes the need for a BMAB in patients with DLBCL remains to be evaluated in a prospective study. Disclosures No relevant conflicts of interest to declare.

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Long term follow-up (FU) of lenalidomide plus R-CHOP therapy in patients with newly diagnosed diffuse large b-cell lymphoma (DLBCL): Combined analysis from two phase 2 trials.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.7562 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 7562-7562 ◽

Cited By ~ 1

Author(s):

Alessia Castellino ◽

Betsy LaPlant ◽

Levi Pederson ◽

Annalisa Chiappella ◽

Gianluca Gaidano ◽

...

Keyword(s):

Cell Lymphoma ◽

B Cell Lymphoma ◽

Phase 2 ◽

Newly Diagnosed ◽

Two Phase ◽

Large B Cell Lymphoma ◽

Long Term Follow Up ◽

Large B Cell

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Chidamide Plus R-CHOP21 in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Results of a Phase II Study

Blood ◽

10.1182/blood-2018-99-113942 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2968-2968 ◽

Cited By ~ 1

Author(s):

Muchen Zhang ◽

Ying Fang ◽

Pengpeng Xu ◽

Shu Cheng ◽

Li Wang ◽

...

Keyword(s):

Elderly Patients ◽

B Cell ◽

Phase Ii Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Grade 3 ◽

Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin's lymphoma and is heterogeneous in clinical, immunophenotypic and genetic features. More than 50% of patients with DLBCL are older than 60 years at diagnosis. Among them, up to 40% of patients relapse or develop refractory disease upon R-CHOP treatment. Dose-dense R-CHOP14 failed to show superior efficacy or survival compared with standard R-CHOP21 in elderly patients and intensive chemotherapy followed by autologous stem cell transplantation was difficult due to toxicity. Therefore, development of new first-line therapy remains great interests to improve disease outcome in elderly patients with DLBCL. Perturbation of the epigenome plays a crucial role in lymphoma progression. Several histone deacetylase inhibitors (HDACIs) have been investigated in relapsed or refractory DLBCL as mono- or combination treatment, showing promising activities to suppress lymphoma growth and overcome resistance to immune-chemotherapies. This prospective phase II study was to evaluate the efficacy and safety of chidamide in combination with R-CHOP21 in elderly patients with newly diagnosed DLBCL (NCT02753647). Methods: Patients with newly diagnosed DLBCL, aged 61 to 75 years, Eastern Cooperative Oncology Group performance status of 0 to 2, IPI>1 were enrolled. The dose and administration schedule were as follows: rituximab 375 mg/m2 on day 0, cyclophosphamide 750mg/m2 on day 1, doxorubicin 50mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, prednisone 60 mg/m2 from day 1 to day 5, chidamide 20mg/d on days 1, 4, 8 and 11, every 21 days for 6 cycles. The primary endpoint was complete response (CR) rate assessed by PET-CT, and secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and main adverse events (AEs). Results: From March 2016 to April 2018, 49 patients were enrolled; 41 patients completed all treatment and 8 patients were still in the treatment cycles. Median age was 67 years (range, 61-75) and 28 patients (57.1%) were male. Thirty-eight patients (77.6%) presented advanced Ann Arbor stage, and 41 patients (83.7%) showed elevated serum LDH level. Thirty-one patients (63.3%) had multiple extra-nodal sites, mainly involving bone, gastrointestinal, liver, and bone marrow. Forty-one patients (83.7%) had IPI scores ≥3 at diagnosis. By immunohistochemistry, 12 (24.5%) patients were categorized as germinal center B-cell (GCB) subtype based on Hans algorithm, and 12 (25.5%) patients were defined as BCL-2 and MYC double expression. Among 41 patients available for evaluation, the CR rate was 85.4% (35/41), and the ORR was 90.3% (37/41). After a median follow-up of 18 months (range, 3-30), the 1-year PFS was 92.1% and 1-year OS was 94.7%. There were 2 deaths due to disease progression, of which 1 had triple-hit lymphoma. Regarding toxicity, grade 3-4 neutropenia was observed in 167 cycles (60.5%), grade 3-4 thrombocytopenia in 27 cycles (9.8%), and grade 3 anemia in 11 cycles (4.0%). However, febrile neutropenia was reported in significantly fewer cycles (6.1%) and was a maximum of grade 3. Grade 3 liver dysfunction was observed in 7 cycles (2.5%). No grade 4 non-hematological events were reported. Of note, 2 patients positive for EBER-ISH at diagnosis remained in EBV-DNA negative during treatment and follow-up. Conclusion: Chidamide with R-CHOP21 is effective and safe in elderly patients with newly diagnosed DLBCL. Disclosures No relevant conflicts of interest to declare.

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