scholarly journals Real-World Data (RWD) on the 3-Year Follow-Up Outcomes of Different CNS Prophylaxis Strategies Across CNS-IPI Risk Groups in Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

2021 ◽  
pp. 486-494
Author(s):  
Anadil Faqah ◽  
Summaiya Asif ◽  
Suleyman Yasin Goksu ◽  
Hassan S. Sheikh
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Relapse Rate ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Large B Cell ◽  
Prophylaxis Strategy

PURPOSE CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis with a median survival of about 2.5 months. Data demonstrating best prophylactic strategy remain controversial and need further definition. PATIENTS AND METHODS We present data of 110 patients with DLBCL treated with standard systemic therapy divided into four groups based on primary CNS prophylaxis strategy and CNS International Prognostic Index (IPI) risk categories. We compared their 3-year CNS relapse rate and overall survival in each group. RESULTS The CNS prophylaxis strategy consisted of intrathecal (IT) methotrexate (MTX) in group 1, high-dose (HD) MTX in group 2, combination IT and HD MTX in group 3, and IT and/or HD MTX with intensive chemotherapy in group 4. At 3 years, CNS relapse rate was 8.6% (4/46), 8.3% (1/12), 4.8% (2/42), and 18% (2/11) in groups 1-4 ( P = .64), respectively. According to CNS IPI, the CNS relapse rate was 16.6%, 10.1%, and 0% in high-, intermediate-, and low-risk groups, respectively. The 3-year overall survival rate was 69%, 75%, 80%, and 45% in groups 1-4 ( P = .71), respectively. CONCLUSION Our study while did not find statistical significance did indicate a lower incidence of CNS relapse with the addition of systemic HD MTX to IT MTX in the high-risk DLBCL population.

scholarly journals Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Sabela Bobillo ◽  
Erel Joffe ◽  
David Sermer ◽  
Patrizia Mondello ◽  
Paola Ghione ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Relapse Risk ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

AbstractAlthough methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.

scholarly journals Intrathecal (IT) Chemotherapy for Central Nervous System (CNS) Prophylaxis in Diffuse Large B-Cell Lymphoma (DLBCL): A Single Centre Retrospective Observational Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Luke Attwell ◽  
Benjamin Gray ◽  
Rachel Hall ◽  
Sally Killick ◽  
Helen McCarthy ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Educational Meetings ◽  
Large B Cell

Introduction: CNS relapse of DLBCL is associated with poor prognosis. Estimated incidence varies between 1.9 and 8.4%1. The CNS-International prognostic index (IPI)2 help risk stratify and estimate the 2-year risk of CNS relapse in DLBCL patients treated with R-CHOP chemotherapy. CNS prophylaxis is indicated in patients with a high risk of CNS relapse (a score of ≥4 equated to a 10.2% risk). High-risk DLBCL patients outside the CNS-IPI system include double/triple-hit (MYC/BCL-2/BCL-6 translocations) lymphoma, HIV lymphoma, testicular lymphoma, primary cutaneous lymphoma-leg type, stage IE breast lymphoma3. IT methotrexate or cytarabine administered during the course of systemic chemotherapy has been the most widely employed method of CNS prophylaxis but there is paucity of data validating its efficacy. Aim: The primary aim of the study was to evaluate the CNS relapse rates in DLBCL patients who received CNS prophylaxis. Patients and Methods: This was a single-centre retrospective observational study conducted in a district general hospital. Data was extracted from the regional (Dorset Cancer Network) DLBCL database and laboratory reports for CSF analysis at the time of the first intrathecal chemotherapy. Medical records of patients with DLBCL who received CNS prophylaxis were evaluated for the following patient-related and disease-related demographics: age at diagnosis, gender, stage, systemic treatment, CNS prophylaxis, treatment response, remission duration, systemic relapse rates, CNS relapse rates and survival. CNS-IPI scores were retrospectively calculated and additional indications evaluated for patients who received CNS prophylaxis. Results: Between 2013 and 2018, 178 patients were diagnosed with DLBCL. All patients were treated with RCHOP chemo-immunotherapy. CNS prophylaxis was administered in 47 (26%) patients. Median age was 69 years (range 20-86 years) and 62% were males. All 47 patients (100%) received IT methotrexate as CNS prophylaxis, with 43 (91%) receiving all of the planned 4 doses of IT methotrexate 12.5 mg each. A CNS-IPI score of ³4 was present in 31 (66%) patients, and a score of 2-3 in 9 (19%) patients. Additional risk factors identified included testicular lymphoma in 3 patients, breast lymphoma in 2 patients and oropharyngeal lymphoma in 2 patients. Ten (21%) patients received their treatment at the outset with courses 1-4 of R-CHOP. Of the 47 patients who received CNS prophylaxis, 5 (10%) relapsed; all had isolated CNS lymphoma at relapse. Median time to CNS relapse was 25 months (range 12-36 months) from initial diagnosis of DLBCL. Median survival after CNS relapse was 5 months (range 2-9 months). Of the remaining 141 patients, 2 patients relapsed with isolated CNS lymphoma. Conclusion: Although the overall incidence was low (4%), CNS relapse was observed in 10% of high-risk patients all of whom received CNS prophylaxis with IT methotrexate. The efficacy of CNS prophylaxis with IT chemotherapy remains unproven. There is no randomised study to show that IT prophylaxis alone is effective. Current British guidelines recommend high-dose intravenous methotrexate over IT methotrexate if patient's physiological fitness and renal function are acceptable4. The median age in our cohort was 69 years which makes it challenging to deliver dose-intensive systemic therapy concurrently with intravenous high-dose methotrexate. The role of CNS prophylaxis in high-risk patients including its efficacy and safety in older patients need further evaluation in prospective randomised studies. References Eyre T et al.Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review. Hematologica. 2019;105(7):1914-1924.Norbert Schmitz et al.CNS International prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOPJ Clin Oncol 2016; 34:3150-3156.Andrew D Zelenetz et al.National Comprehensive Cancer Network (NCCN) Guidelines: B-Cell Lymphomas.Version 2.2020.Pamela McKay et al.The prevention of central nervous system relapse in diffuse large B-cell lymphoma: a British Society for Haematology good practice paper. Onlinelibrary.wiley.com. 2020. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16866 Disclosures Hall: Janssen:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Karyopharm:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Takeda:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings.Killick:Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Jazz Pharmaceuticals:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Gilead:Honoraria, Other: Support for attending education meetings.McCarthy:Janssen:Honoraria;Abbvie:Membership on an entity's Board of Directors or advisory committees.Walewska:AbbVie:Other: sponsored for educational meetings, Speakers Bureau;Janssen:Other: sponsored for educational meetings, Speakers Bureau;Gilead:Speakers Bureau;Astra Zeneca:Membership on an entity's Board of Directors or advisory committees.Chacko:Astellas:Honoraria;Daiichi-Sankyo:Honoraria;Novartis:Honoraria, Other: Travel Grants;Gilead:Other: Travel grants;Jazz Pharmaceuticals:Other: Travel grants;Celgene:Other: Travel grants.

Central Nervous System Relapse in Patients with Diffuse Large B-Cell Lymphoma: Analysis of Incidence and Prognostic Factors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1666-1666
Author(s):  
Masahiro Uni ◽  
Yuki Kagoya ◽  
Yasuhito Nannya ◽  
Fumihiko Nakamura ◽  
Mineo Kurokawa
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Initial Diagnosis ◽  
High Dose ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

Abstract The addition of rituximab to CHOP (R-CHOP; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisolone) has significantly improved the outcome of diffuse large B-cell lymphoma (DLBCL). However, its secondary involvement in the central nervous system (CNS) is still a fatal event, and optimal therapeutic strategies have remained to be established. Combined immunochemotherapy with rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy and high-dose cytarabine is currently in use for patients with CNS relapse, though treatment outcome has not been evaluated enough. In the present study, we aimed to analyze the incidence and prognosis of CNS relapse of aggressive B-cell lymphoma in comparison with those of systemic relapse in the era of rituximab-containing regimens. We also estimated the risk factors and prognostic factors for CNS relapse. We retrospectively analyzed 278 consecutive adult patients (≥16 years old) who were diagnosed as DLBCL or primary mediastinal large B-cell lymphoma (PMLBL) at The University of Tokyo Hospital, Tokyo, Japan, from August 2003 through August 2013. We excluded patients who had CNS or intraocular involvement at diagnosis since those patients had received high-dose methotrexate-based therapy instead of R-CHOP. Four to six courses of intrathecal administration of methotrexate were performed in patients with adrenal gland, testis or breast involvement as prophylaxis for CNS relapse. The median follow-up period was 42 months, and the median age was 66 years (range, 23-91). Overall, 67 patients (24.1%) had relapse at any site, of which 24 patients (35.8%) had CNS involvement. The median interval between initial diagnosis and the occurrence of secondary CNS involvement was 212 days, and 15 of the 24 patients (62.5%) had CNS relapse within 1 year from the initial diagnosis. Multivariate analysis revealed that multiple or diffuse extranodal involvement at initial diagnosis (hazard ratio [HR] 3.74, 95% confidence interval [CI] 1.28-10.91; P<0.01) was associated with the development of CNS relapse against non-CNS relapse. Chromosomal abnormality was investigated in 112 patients, of which 38 had abnormal karyotypes as identified by G-banding analysis for lymph nodes. Patients with CNS relapse more frequently harbored chromosomal abnormalities compared with those without relapse in univariate analysis (P=0.01). We also analyzed the survival of patients with primary CNS lymphoma (PCNSL) as a control. Only two (7%) of 27 patients with PCNSL died during the follow-up period. Five-year OS from initial diagnosis was 92.3% (95% CI: 82.5-100.0%), and was significantly better than that for patients with CNS relapse (33.9%, 95% CI: 17.3-66.3%, P<0.01). Among 24 patients with CNS relapse, eight (33%) had systemic lesions other than CNS when diagnosed as CNS relapse, and four (17%) patients newly developed systemic lesions while treated for CNS relapse. Patients without concurrent systemic lesions attained a rather good prognosis by chemo-radiotherapy, while those harboring concurrent systemic lesions had dismal outcome (one-year OS after the diagnosis of relapse: 74.0% versus 12.4%, P<0.01, Figure 1, systemic relapse was treated as a time-dependent covariate). These results indicate that controlling systemic lesions as well as CNS ones is essential for treating patients with secondary CNS involvement of DLBCL. CNS lesions would be well controlled with R-MPV implementation as salvage therapy, nevertheless we should be careful for concurrent systemic lesions which might require different therapeutic strategies. Disclosures Nannya: Chugai Pharmaceutical　CO., LTD: Speakers Bureau; Pfizer: Research Funding. Kurokawa:Chugai Pharmaceutical　CO., LTD: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding.

scholarly journals Favorable Outcomes with Thiotepa/Busulfan-Based Conditioning and Autotransplant for Patients with Aggressive B-Cell Lymphoma and Secondary CNS Involvement

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2912-2912
Author(s):  
Robert Puckrin ◽  
Neil Chua ◽  
Mona Shafey ◽  
Douglas A. Stewart
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell ◽  
Aggressive B Cell Lymphoma

Abstract Introduction : Central nervous system (CNS) relapse is a devastating complication affecting ~5% of patients with diffuse large B-cell lymphoma (DLBCL). The optimal management is unknown and survival rates are ~20% in contemporary series. Thiotepa/busulfan-based high-dose chemotherapy (HDT) and autotransplant (ASCT) has demonstrated efficacy in primary CNS lymphoma, but there have been fewer studies of this conditioning regimen in secondary CNS lymphoma (SCNSL). Methods : This multicenter retrospective study included all consecutive patients ≥18 years old with aggressive B-cell lymphoma and secondary CNS involvement treated with thiotepa/busulfan-based HDT/ASCT at the University of Calgary and University of Alberta since 2005. Kaplan-Meier curves were used to estimate progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) from the time of ASCT. Data collection is underway for all consecutively diagnosed SCNSL patients at our institutions to evaluate frequency and predictors of HDT/ASCT use. Results : This study included 57 patients with DLBCL (n=45), double-hit lymphoma (n=6), high-grade B-cell lymphoma NOS (n=2), intravascular large B-cell lymphoma (n=2), or T-cell/histiocyte-rich large B-cell lymphoma (n=2). Two (4%) had previously treated indolent B-cell lymphoma and 1 (2%) had multiply relapsed DLBCL. Median International Prognostic Index was 4 (range 0-5) at DLBCL diagnosis and median time to CNS relapse was 4 months (range 0-139). Median age was 58 years (range 20-73) and median ECOG was 3 (range 0-4) at diagnosis of SCNSL. CNS involvement was present at initial diagnosis in 20 (35%) patients or developed during frontline treatment in 10 (18%) or after completion of treatment in 27 (47%). For those without SCNSL at diagnosis, isolated CNS relapse occurred in 31 (84%) patients while 6 (16%) had concurrent CNS and systemic relapse. Most patients (n=54, 94%) received high-dose methotrexate (HD-MTX)-based multiagent induction chemotherapy (median HD-MTX doses 4, range 1-5) followed by peripheral blood stem cell mobilization with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in 41 (72%). HDT conditioning regimens were thiotepa, busulfan, melphalan, rituximab (TBMR, n=52, 91%) or thiotepa, busulfan, cyclophosphamide (TBC, n=5, 9%). Median time from SCNSL diagnosis to ASCT was 116 days (range 7-201). Median time to neutrophil engraftment was 10 days (range 7-15) and to platelet engraftment 16 days (range 9-93). Overall response rates (ORR) for systemic/CNS disease were 93%/89% pre-ASCT and 95%/100% post-ASCT. Combined ORR pre-ASCT was 88%, with complete response in 21% and partial response in 67%. Two (4%) patients who developed CNS relapse immediately prior to ASCT achieved long-term remission after TBMR conditioning without any other systemic chemotherapy. With a median follow-up time of 4.0 years (range 0.1-15.9), PFS was 75% (95% CI 61-85%), OS was 76% (95% CI 62-86%), and DSS was 79% (95% CI 64-88%) at 4 years after ASCT. Lymphoma recurred in 9 (16%) patients at median 88 days (range 54-346) after ASCT with CNS relapse (n=4), systemic relapse (n=3), or both (n=2). There were 2 (4%) deaths due to peri-transplant toxicity and 1 (2%) death at 1.5 years due to therapy-related acute myeloid leukemia; no other unexpected toxicities of HDT/ASCT were observed. Among the 45 (79%) patients achieving long-term disease-specific survival, none were treated with CNS radiation therapy and only 1 (2%) had persistent neurocognitive impairment. There were no significant differences in DSS with respect to timing of CNS relapse, concurrent presence of systemic disease, or TBMR versus TBC conditioning (78% vs 80%, p=0.87). Conclusion : In one of the largest studies of this conditioning regimen in SCNSL to date, we found that high-dose thiotepa/busulfan-based conditioning with ASCT is associated with favorable outcomes for patients with aggressive B-cell lymphoma and secondary CNS involvement, with 4-year OS ~75% in this study. Although SCNSL has been historically associated with a poor prognosis, an increasing proportion of patients may achieve long-term survival after intensive therapy with HD-MTX-based induction and thiotepa/busulfan-based HDT and ASCT. Figure 1 Figure 1. Disclosures Chua: Eisai: Honoraria; Pfizer: Honoraria; Merck: Honoraria; Gilead: Honoraria. Stewart: Novartis: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria; Sandoz: Honoraria; Teva: Honoraria.

scholarly journals Efficacy and safety of prophylactic high-dose MTX in high-risk DLBCL: a treatment intent–based analysis

2021 ◽  
Vol 5 (8) ◽  
pp. 2142-2152
Author(s):  
Hyehyun Jeong ◽  
Hyungwoo Cho ◽  
Hyeyeong Kim ◽  
Heejung Chae ◽  
Jung-Bok Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Relapse Rate ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Survival Outcomes ◽  
High Dose ◽  
Free Survival ◽  
Cns Relapse ◽  
Treatment Intent

Abstract Despite central nervous system (CNS) relapse occurring in &gt;10% of high-risk diffuse large B-cell lymphoma (DLBCL) patients, the role of CNS-directed prophylaxis is controversial in the absence of randomized controlled trials. In this retrospective study, we aimed to evaluate the safety and efficacy of prophylactic high-dose methotrexate (HD-MTX) on CNS relapse and survival outcomes in 258 newly diagnosed R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–treated high-risk DLBCL patients, based on the initial treatment intent (ITT) of the physician on the use of prophylactic HD-MTX. Patients were classified into an ITT HD-MTX group (n = 128) and a non-ITT HD-MTX group (n = 130). The CNS relapse rate was not significantly different between these groups, with 2-year CNS relapse rates of 12.4% and 13.9%, respectively (P = 0.96). Three-year progression-free survival and overall survival rates in the ITT HD-MTX and non-ITT HD-MTX groups were 62.4% vs 64.5% (P = 0.94) and 71.7% vs 71.4% (P = 0.7), respectively. Also, propensity score–matched analyses showed no significant differences in the time-to-CNS-relapse, progression-free survival, or overall survival. The ITT HD-MTX group showed a higher incidence of grade ≥ 3 oral mucositis and elevated alanine aminotransferase. Prophylactic HD-MTX does not improve CNS relapse rate or survival outcomes in high-risk DLBCL patients, and it is accompanied by increased toxicities.

Retrospective analysis of CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) treated with chemotherapy with or without rituximab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8551-8551
Author(s):  
K. Miyazaki ◽  
M. Yamaguchi ◽  
R. Suzuki ◽  
N. Niitsu ◽  
D. Ennishi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Elevated Serum ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Significant Difference ◽  
Large B Cell

8551 Background: CD5+ DLBCL comprises 5–10% of DLBCL, and shows a high incidence of central nervous system (CNS) relapse. It has been included in the 4th WHO classification as an immunohistochemical subgroup. To clarify the prognosis and incidence of CNS relapse of CD5+ DLBCL in the rituximab-era, we conducted a multicenter retrospective study. Methods: We analyzed 313 patients (pts) with CD5+ DLBCL who received chemotherapy with (n=164) or without rituximab (n=149). The current series includes 107 out of 120 pts described in our previous study (Haematologica, 2008). Intravascular large B-cell lymphoma, primary CNS DLBCL, and secondary CD5+ DLBCL were excluded from the study population. Results: 313 pts showed the following clinical features: median age, 67 (range: 15–93); M:F=163:150; elevated serum LDH level, 71%; stage III/IV, 64%; IPI HI/H, 53%. No significant difference in clinical background such as the IPI and its five components, B symptom, male sex, and bone marrow involvement was found between pts who were treated with and without rituximab. Pts treated without rituximab received more dose-intensive chemotherapies (CHOP14, third-generation regimen, and high dose cytarabine-based regimen) than those treated with rituximab (24% vs. 7%, P<0.0001). The CR rate was higher in pts received rituximab than those without (81% vs. 65%; P=0.0014). The median follow-up was 28 months in pts who received rituximab (range: 7–77) and 68 months in those who did not (range: 6–187). Overall survival (OS) was significantly superior for pts with rituximab than for those without (2-yr OS: 68% vs. 54%, P=0.003). Multivariate analysis revealed that the use of rituximab was favorably associated with OS (HR=1.81, 95% CI: 1.26–2.58, P=0.001), but dose-intensive chemotherapies did not affect OS. However, the incidence of CNS relapse was not different between the two groups (2-yr CNS relapse rate: 11.9% vs. 11.4%, P=0.91). 16 of the 20 pts (80%) with CNS relapse in the rituximab group had brain parenchymal disease. Conclusions: Our data show that rituximab improves OS of pts with CD5+ DLBCL, but does not prevent CNS relapse. Future prospective studies to decrease CNS disease for CD5+ DLBCL are warranted. No significant financial relationships to disclose.

scholarly journals Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubucin and Rituximab (da-EPOCH-R) Vs Rituxan, Cyclophosphamide, Doxorubucin, Vincristine and Prednisone (R-CHOP) As First Line Treatment for Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5410-5410
Author(s):  
Parikshit Padhi ◽  
Abhishek Chilkulwar ◽  
Cyrus Khan ◽  
Monank Patel ◽  
John Lister ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Relapse Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Objectives: To assess the efficacy and safety of da-EPOCH-R as frontline treatment for patients diagnosed with Stage III/IV Diffuse Large B-Cell Lymphoma. Methods: We conducted a retrospective study of newly diagnosed patients with advanced Diffuse Large B-Cell Lymphoma from January 2008 till September 2015, who received frontline da-EPOCH-R or R-CHOP at our Health System. We excluded patients with primary CNS lymphoma, primary testicular lymphoma and patients who received chemotherapy for a prior lymphoma. 25 patients who received da-EPOCH-R and 50 patients who received R-CHOP were identified. Da-EPOCH-R regimen consisted of Etoposide 50mg/m2/day, Doxorubucin 10mg/m2/day and Vincristine 0.4mg/m2/day given on Days 1-4, Cyclophosphamide 750mg/m2 on Day 5, Prednisone 60mg/m2 twice a day from Days 1-6 and Rituximab 375mg/m2given on Day 5. On Day 6 G-CSF was administered. Each cycle was given every 21 days for a total of 6 cycles. The dose of Etoposide, Doxorubucin and Cyclophosphamide was adjusted according to standard protocols. All patients on the da-EPOCH arm were on Acyclovir, Ciprofloxacin, Fluconazole and Trimethoprim-Sulfamethoxazole for anti-microbial prophylaxis during their treatment. The use of growth factors and anti-microbial prophylaxis was inconsistent in the R-CHOP arm. Results: When comparing the da-EPOCH-R arm versus the R-CHOP arm, the average age of the patients was 50 years (25-81) vs 60 years (19-84). High-risk IPI was similar in both arms (76% vs 74%). The percentage of non-germinal center type (non-GCB) was equal as well (36% vs 32%). The average number of cycles administered was 5.3 compared to 4.8. There were more dose reductions in the da-EPOCH-R arm (36% vs 24%), however fewer delays and cessations were noted (36% vs 54%). After a median follow up of 29.1 months, the age-adjusted overall survival (77% vs. 69%, p=0.093) and disease-free survival (76% vs. 55% p=0.54) was improved in the da-EPOCH-R arm. In the non-GCB variant da-EPOCH improved overall survival by 77% (p=0.024). The Overall Response Rate was higher in the da-EPOCH-R arm 80% (CR/CRU=64% and PR=16%) vs. 56% (CR/CRU=44% and PR=12%). The relapse rate was lower in the da-EPOCH-R arm (16% vs 28%), and it was lower in the non-GCB patients as well (11% vs 25%). There were more Grade 3-4 neutropenia in the da-EPOCH arm (72% vs 48%), however infectious complications were lower (24% vs 42%). There were fewer unplanned admissions in the da-EPOCH arm (32% vs 60%) and a significantly lower treatment related mortality (12% vs 22%). Other Grade 3-4 toxicities too were lower in the da-EPOCH-R arm (20% vs 30%). Conclusion: Our preliminary results suggest that da-EPOCH-R has a survival benefit especially in the non-GCB subgroup. Our data does show good survival data even for the GCB subtypes. There was a higher response rate, lower relapse rate and no added toxicities in patients who received da-EPOCH-R. A Phase III trial is currently ongoing and will provide us with answers regarding the efficacy and toxicities of this chemotherapy regimen. Disclosures No relevant conflicts of interest to declare.

Rituximab Based Regimen May Decrease the Incidence of CNS Relapse in Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4770-4770
Author(s):  
Mervat Mahrous Mohamed ◽  
Rena Buckstein ◽  
Eugenia Piliotis ◽  
Matthew C Cheung ◽  
Neil Berinstein
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Cns Involvement ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 4770 BACKGROUND Relapse in the central nervous system (CNS) following initial treatment of diffuse large B-cell lymphoma (DLBCL) is an uncommon but fatal complication. However, the addition of rituximab improves the clinical outcome dramatically in DLBCL patients; its influence on CNS relapse is unproven. Aim This single centre retrospective study was conducted to investigate the incidence of CNS relapse, and to evaluate the impact of adding rituximab to standard CHOP (RCHOP) regimen without CNS prophylaxis in patients at risk of CNS relapse. PATIENTS AND METHODS All patients with DLBCL diagnosed from April 2002 to December 2007 at sunnybrook cancer center were retrospectively identified in the Cancer Database. Patients were included if they were >16 years old, had advanced stage (stage III /IV, or stage I /II with B symptoms, elevated LDH or bulky disease, were treated with RCHOP regimen with curative intent and were free of CNS involvement at diagnosis. CNS relapse was diagnosed by CSF cytology, radiology or clinically. Results A total of 155 patients were newly diagnosed with DLBCL and treated with RCHOP only. 22 pts were excluded, 20 had CNS prophylaxis and 2 pts had CNS involvement. 133 pts were eligible (69 male and 64 female) Median age was 64 (Age'60 was 59.4%). Stage III/IV was 69.9%. LDH was elevated in 59.4%. Bone marrow (BM) involvement and Extra nodal “>2 were 18.05% and 25.6% respectively. EN sites were: (liver 4.5%, Bone 6.8%, Pulmonary 4.5%, kidney 3.01%, cardiac 1.5%, intestine 2.3%, testicular 1.5%). The International Prognostic Index was high-intermediate/high in 55.6%. Pathologically transformed was 12.03% and were transformed from indolent histologies. BCL2 was positive in 65.4%, BCL6 was 48.9%, CD10 was positive in 49.6%, Ki-67 was >80% in 25%. All patients received RCHOP (Median 6 cycles, (range 2-8). Overall response (ORR) was 88.6%, CR/CRU 72.7% with a median follow up 24.6 months (range 2.6-75.5). 28 patients (21.05%) relapsed systemically. Two patients (1.5%) had a CNS relapse 1 brain parenchyma and 1 leptomeningeal one month after systemic relapse. The median time to CNS relapse was 10.4 mos (6.24-14.5 mos). In univariate risk factor analysis (LDH (p=0.8), IPI>3 (p=0.9), No of EN (p=0.9). Actuarial 5 y Overall Survival (OS) was 67.3% (95% CI (57-77%) and progression free Survival (PFS) was 65.7% (95% CI (52.3-78.6%). Conclusion Our data suggest that the addition of rituximab may reduce the risk of CNS relapse for poor risk patients likely through systemic control. Future prospective studies of rituximab-containing chemotherapies with CNS prophylaxis are warranted Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Diving Bell and the Butterfly Revisited: A Fatal Case of Locked-in Syndrome in a Man With Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

2018 ◽  
Vol 11 ◽  
pp. 1179545X1876279
Author(s):  
Jacqueline N Poston ◽  
Russell Dorer ◽  
David M Aboulafia
Keyword(s):  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Epstein Barr ◽  
Large B Cell

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare variant of DLBCL. The natural history of this subtype is poorly understood. Incomplete literature in the era of rituximab suggests that patients with EBV-positive DLBCL have similar outcomes to patients with EBV-negative DLBCL when treated with rituximab and anthracycline-based chemotherapy regimens; however, there are few prospective studies on this subtype and little is known about the risk of central nervous system (CNS) relapse with EBV-positive DLBCL. Herein, we describe the case of a 64-year-old man who presented with stage IIA EBV-positive DLBCL. His international age-adjusted International Prognostic Index (IPI) was 2. He achieved a complete response to 6 cycles of rituximab combined with chemotherapy consisting of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. After 10 days of completion of chemotherapy, he had a fulminant neurologic decline manifested by diffuse weakness followed by a locked-in syndrome; he could only communicate by moving his eyes. He had been deemed at low risk for CNS relapse based on the application of the recently developed CNS-IPI score of 2 (1 point for age >60 years and 1 point for lactate dehydrogenase higher than normal) and consequently did not receive therapy for CNS prophylaxis. A limited postmortem autopsy revealed extensive lymphoma throughout the brain, particularly in the deep basal nuclei, midbrain, pons, centrum semiovale, and corpus callosum. This presentation of CNS relapse is rare and has not yet been described in EBV-positive DLBCL. We discuss some of the unique aspects of this case including the clinical manifestations of locked-in syndrome and its differential diagnosis and the uncertain benefits of CNS prophylaxis in this clinical context.

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