Rituximab-CHOP (R-CHOP) and Radiotherapy (RT) for Primary Mediastinal Large B-Cell Lymphoma (PMLBCL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2745-2745 ◽  
Author(s):  
Theodoros P. Vassilakopoulos ◽  
Maria K. Angelopoulou ◽  
Zacharoula Galani ◽  
Sotirios Sachanas ◽  
Andreas Katsigiannis ◽  
...  

Abstract Background: MACOP-B or even chemotherapy (CT) with consolidation high dose therapy with autologous stem cell support (HDT-ASCT) have been considered superior to CHOP in PMLBCL. However, in the absence of randomized trials, there is no established optimal treatment for these patients. The role of R-CHOP in PMLBCL, which usually affects young patients, has not been established. Aims: To evaluate the efficacy of R-CHOP±RT in PMLBCL and to compare this approach with CHOP±RT administered to historical controls. Patients and Methods: Between 1994 and 2006, 74 patients with PMLBCL were treated in 6 participating centers. R-CHOP displaced CHOP in the treatment of PMLBCL at a given timepoint in each center. Thus 31 consecutive patients who received R-CHOP, were compared with 43 consecutive historical controls, who had been treated with CHOP prior to that point. Results: The median age of the patients was 30 years (17–82), only 2 patients (3%) were older than 60 years, and 47/74 (64%) were females. All individual IPI parameters as well as B-symptoms were also balanced between the two groups, with the exception of performance status. The median follow-up of currently alive patients was 28 and 73 months for patients treated with R-CHOP±RT and CHOP±RT respectively, the complete response (CR/CRu) rate was 97% vs 67% (p=0.002), and the overall response rate was 100% vs 79%, respectively (p=0.007). All relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 93±5% vs 53±8% for patients who received R-CHOP±RT vs CHOP±RT (p=0.0006). Within the subgroup of patients with L/LI risk IPI, the corresponding 3-year FFS rates were 95±5% vs 58±10% (p=0.007), while they were 90±9% vs 45±12% (p=0.03) among patients with HI/H risk IPI. The 3-year event free survival (EFS) for all patients was 90±5% vs 51±8% (p=0.001). The 3-year overall survival (OS) was 97±3% vs 67±7% (p=0.008), while the 3-year lymphoma specific survival (LSS) was 100% vs 67±7% (p=0.002). Conclusions: R-CHOP and RT provided impressive results with no cases of primary refractory disease, no lymphoma-related deaths and only 2 failures recorded so far after a median follow-up of 28 months among 31 patients. Patients treated with R-CHOP had significantly higher CR, FFS, EFS, OS, and LSS rates, when compared with CHOP-treated historical controls. Based on these results we continue to treat PMLBCL patients with R-CHOP and RT, avoiding more intensive strategies. Further studies are warranted to investigate whether RT is needed after R-CHOP, especially in the case of a negative post-chemotherapy PET-scan.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 935-935 ◽  
Author(s):  
Theodoros P. Vassilakopoulos ◽  
Maria K. Angelopoulou ◽  
Zacharoula Galani ◽  
Sotirios Sachanas ◽  
Andreas Katsigiannis ◽  
...  

Abstract Introduction: Combination chemoptherapy regimens such as CHOP and MACOP-B with or without RT are considered the standard first-line treatment for PMLBCL patients. Consolidation with high dose therapy and autologous stem cell support (HDT-ASCT) at first remission is an alternative approach for this young population. However results are not optimal. Given the superiority of R-CHOP over CHOP in elderly patients with diffuse large B-cell lymphoma, the role of Rituximab added to first-line chemotherapy in younger patients is not clear. Aims: In this study we evaluate the effectiveness of R-CHOP±RT in PMLBCL and we compare the results of this strategy to CHOP±RT in historical controls. Patients and Methods: A total of 46 patients with PMLBCL were treated in two participating centers between 1994 and 2004. At a given timepoint R-CHOP replaced CHOP in both centers. Thus, 31 consecutive historical controls were treated with CHOP prior to that point and were compared to 15 patients who received R-CHOP thereafter. Results: The median age of the patients was 31 years (17–58) and 32/46 (70%) were females. Baseline characteristics between the R-CHOP and CHOP groups were well balanced, including age-adjusted IPI [ ≥2 in 40% of R-CHOP and 42% of CHOP-treated patients (p=0.90)]. Complete response (CR) was achieved in 100% in the R-CHOP±RT vs 61% in the CHOP±RT group (p=0.009). No patient has relapsed after R-CHOP, while all relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 100% and 47±9% for patients treated with R-CHOP±RT and CHOP±RT respectively(p=0.005). Within the subgroup of patients with L/LI risk IPI the corresponding 3-year FFS rates were 100% vs 61±11% (p=0.059), while they were 100% vs 26±13% (p=0.02) among patients with HI/H risk IPI for R-CHOP±RT and CHOP±RT respectively. The 3-year event free survival (EFS) was 93±7% vs 47±9% (p=0.02). The 3-year overall survival was 93±7% vs 47±9% (p=0.27), while the 3-year lymphoma specific survival was 100% vs 67±9% (p=0.049) for the R-CHOP and CHOP groups respectively. Conclusions: R-CHOP±RT exhibited impressive efficacy with no failures among 15 patients. CR and FFS rates were significantly better in favor of R-CHOP compared to CHOP-treated historical controls. EFS and lymphoma specific survival were also improved. Based on these data, our standard approach for PMLBCL patients is the application of R-CHOP±RT. Furthermore the addition of Rituximab to front-line treatment might overcome the need for more aggressive strategies such as consolidation with HDT-ASCT in this patient population.


MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Rachel Wong ◽  
Roopesh R. Kansara

Introduction Dose adjusted (DA) EPOCH-R is an intensive outpatient infusional regimen, that incorporates intrathecal (IT) methotrexate to treat patients with aggressive B-cell lymphoma including HIV associated aggressive B-cell lymphoma, double-hit lymphoma (DHL), primary mediastinal B-cell lymphoma (PMBCL), Burkitt's lymphoma (BL) ineligible for intensive therapy, and gray zone lymphoma (GZL) with features in between BL and diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate non-trial, progression-free survival (PFS) and overall survival (OS) of Manitoba patients treated with DA-EPOCH-R, assess the role of prophylactic IT chemotherapy and toxicities. Methods Patients in MB approved to receive DA-EPOCH-R were identified through the CCMB Provincial Oncology Drug Program (PODP) database. Patients were included if they were older than 17 years, received at least 1 cycle of DA-EPOCH-R and with a diagnosis of HIV associated aggressive B-cell lymphoma, DHL, PMBCL, BL ineligible for more aggressive therapy, or GZL. All other diagnoses were excluded. Baseline demographic data, treatment characteristics, treatment responses, and treatment toxicity were collected. The primary endpoints of the study were progression free survival (PFS) and overall survival (OS). PFS was the time interval between the date of diagnosis to date of progression, last follow-up, or death from any cause. OS was the time interval between date of diagnosis to date of death by any cause, or last follow-up. The study was approved by the University of Manitoba Research Ethics Board and the CancerCare Manitoba Research Resource Impact Committee. Results A total of 40 patients were approved for DA-EPOCH-R between 2013 and 2019. 10 of these patients were excluded. 4 patients never received the therapy, 4 patients were treated in the relapsed setting, and 2 patients had histologies outside the inclusion criteria. Of the 30 patients included, 19 (63%) were male, 11 (37%) were female. The median age at diagnosis was 55 years (range 20-88). Our cohort was composed of DHL (n=9), triple hit lymphoma (THL, n=5), BL (n=4), GZL (n=3), and HIV-associated DLBCL (n=2). 87% (n=26) had advanced stage disease. By revised-IPI, 19 (63.3%) had poor prognosis (R-IPI ≥ 3). Response rate was 90%; CR 53.3% (n=16) and PR 37% (n=11). At a median follow-up of 25.3 months, the median PFS was 33.3 months and median OS was not reached. By histological subtype, median PFS was not reached in DHL, however THL, BL and PMBCL had worse median PFS (6.1, 8.4, and 5.6 months, respectively). Only 1 patient had CNS involvement at time of diagnosis. Of the patients with no documented CNS disease at presentation (n=29), none developed CNS involvement, including those who did not receive IT methotrexate. Median chemotherapy cycles per patient was 6 (range 1-6) and median IT treatment was 3 (range 0-6). 3 patients did not receive IT prophylaxis, and 2 stopped after 1 cycle due to intolerance. 56.7% (n=17) were able to undergo dose escalation beyond dose level 1, and 40% (n=T12) tolerated maximum dose level 3 or higher.77% of patients (n=23) experienced at least one adverse event of grade 3 or higher. 17 (57%) patients required blood transfusion at least once. 10 (33%) experienced neuropathy, 4 requiring vincristine dose reduction. 9 (30%) patients had febrile neutropenia complicating a total of 22 treatment cycles. 8 patients had grade 2-3 infectious complications. Conclusions While the real-world survival data for patients with DHL and HIV-associated lymphoma treated with DA-EPOCH-R are encouraging, those with THL, BL, and PMBCL did not attain durable response. Considering no patients (including those who did not receive IT chemotherapy) experienced CNS relapse, the role of IT chemotherapy needs to be further clarified. Disclosures No relevant conflicts of interest to declare.


1987 ◽  
Vol 5 (6) ◽  
pp. 918-926 ◽  
Author(s):  
M S Tallman ◽  
F R Appelbaum ◽  
D Amos ◽  
R S Goldberg ◽  
R B Livingston ◽  
...  

In order to test the toxicity and efficacy of intensive postremission therapy with high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide in adults with acute nonlymphocytic leukemia (ANL), 100 adults (ages 19 to 75) with previously untreated ANL were entered into a study using six sequential cycles of chemotherapy. Cycles 1 (induction), 3, and 5 included conventional doses of daunomycin, cytosine arabinoside, 6-thioguanine, vincristine (VCR), and prednisone. Cycle 2 was cytosine arabinoside 3 g/m2 intravenously (IV) every 12 hours for four doses, followed by L-asparaginase 10,000 U intramuscularly (IM) at hour 42; this combination was repeated 1 week later. Cycle 4 included amsacrine 120 mg/m2/d and etoposide 100 mg/m2/d, both IV for five days, and cycle 6 was three monthly courses of VCR on day 1, and prednisone, mercaptopurine, and methotrexate each for five days. Seventy-four patients (74%) achieved complete remission (CR) (51 with cycle 1 and 23 after cycle 2). The overall disease-free survival (DFS) for patients achieving CR is 27% at 3 years by Kaplan-Meier analysis, while for patients achieving CR with cycle 1 it is 34%. The actuarial probability of being free from relapse at 3 years for patients achieving CR is 34%. Sixteen of the 74 CR patients (22%) died in CR while continuing to receive intensive chemotherapy, including 12 (18%) who succumbed to infection (nine bacterial, three fungal). After a median follow-up of 20 months, 36 patients have relapsed and 21 remain alive in CR. Intensive consolidation with high-dose cytosine arabinoside, amsacrine, and etoposide can modestly prolong DFS compared with historical controls. However, relapse continued to be a major problem and, in addition, with more aggressive consolidation therapy, infection during marrow aplasia resulted in a significant number of deaths.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3331-3331
Author(s):  
Marylou Nesbitt ◽  
Kenneth A. Ault ◽  
Fred Aronson ◽  
Marjorie A. Boyd ◽  
Delvyn Caedren Case ◽  
...  

Abstract Background: High Dose Chemotherapy with Autologous Hematopoietic Progenitor Cell Support (HDC/AutHPCS) is a cancer treatment which provides potential for improved survival and risk for short and long term treatment side effects. Self report of QOL outcomes can guide risk assessment and system improvements to optimize care and rehabilitation. Purpose: This study examined and compared over time, the quality of life outcomes for patients who have undergone this treatment. Design: The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT v.3) was the survey instrument used to measure QOL. Respondents were also asked to report their performance status based on the Eastern Co-operative Oncology Group (ECOG) and the New York Heart Association (NYHA) Performance status scales. Two open-ended questions were asked: what ”Good”, or “Bad” things occurred related to the treatment. Additional questions were asked about sleep problems that occurred after transplant, and whether a structured exercise program would have helped after discharge. Method: A survey was mailed in November, 2005. Sample: Patients (n=145) who had this treatment at our institution were contacted by mail. Diagnoses included acute myeloid leukemia, lymphoma, multiple myeloma, amyloid, breast cancer, and testicular cancer. Data analysis: Scores for the FACT-BMT were analyzed using SPSS 14 (SPSS Inc., Chicago IL). Qualitative responses were analyzed using NVivo v.7 software. Results: The return rate was 57% (n=81). The FACT-BMT Scores, subscales and total scores were comparable to other findings in similar studies and populations. FACT BMT SCORES 2006 FactG Score (Mean+/−SD) Range(0–112) 89.24+/−17.32 (45–112) FACT BMT Score (Mean+/−SD Range (0–40) 29.14+/−6.37 (16–40) FACTG/BMT Total (Mean+/−SD) Range (0–152) 118.29+/−22.78 (61–152) There were no statistically significant differences in scores from past studies with this population at this institution. Significant correlations were found between the scores of items in the FACT-BMT for which ≥ 25% of respondents reported low item ratings and the self rating ECOG and/or NYHA performance scales. Significant differences were also found when comparing the FACT-BMT Scores, subscales and total scores with demographic attributes such as, marital status, living situation, health insurance, employment status, and income. Twenty-five per cent (n=21) of respondents described new problems with sleep and 54% (n= 41) of respondents reported that a structured exercise program would have been beneficial for recovery. There were 21 respondents who participated in this survey (2006) and two prior surveys (1997 and 1999). Content and themes of their unsolicited and solicited written responses of their self reported lived experiences over time will be presented. Conclusions: Overall, participants reported good quality of life. Based on demographics, there were subgroups identified potentially needing assessments and interventions focused on physical, social, emotional, and functional well being. This could be accomplished through a more focused pre-admission and follow-up needs assessment to identify patients who would potentially benefit from additional resources for psychosocial support, sleep and exercise/activity issues.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 833-833 ◽  
Author(s):  
Jorge Romaguera ◽  
Luis Fayad ◽  
Alma Rodriguez ◽  
Fb Hagemeister ◽  
Barbara Pro ◽  
...  

Abstract MCL has a poor outcome with current non-intense therapies. We present an update of our results utilizing an intense chemotherapy regimen comprising fractionated cyclophosphamide, doxorubicin, vincristine and dexamethasone to which rituximab has been added (R-HyperCVAD, one cycle), alternating with rituximab and high dose methotrexate/cytarabine (R-MA, one cycle) for a total of 6–8 cycles (J Clin Oncol 2006 Feb 1;24(4):724). Treatment was started at most within 2 months from the initial evaluation. Overall survival (OS) was defined as the time from start of treatment until recurrence or death from any cause. Failure-free survival (FFS) was defined as the time from start of treatment until recurrence or death from toxicity or death from treatment-related malignancy. Of 97 consecutive evaluable patients, 87% achieved a complete response (CR) or unconfirmed CR after 6 cycles and did not receive additional therapy. With a median follow up on 84 months (7 years), the overall survival and failure-free survival at 7 years was 60% and 43%, respectively. Among patients 65 years of age or younger, the 7-year OS and FFS was 68% and 52%, respectively. Important prognostic variables included age (65 yrs or less vs > 65 yrs; initial serum B2 microglobulin 3 or less mg/dL vs > 3); and initial serum lactate dehydrogenase (normal vs > normal). Further subset analysis will be presented at the meeting. Figure Figure


2015 ◽  
Vol 33 (33) ◽  
pp. 3903-3910 ◽  
Author(s):  
Andrés J.M. Ferreri ◽  
Giovanni Donadoni ◽  
Maria Giuseppina Cabras ◽  
Caterina Patti ◽  
Michael Mian ◽  
...  

Purpose Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma. Patients and Methods HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients. Results Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 106/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ± 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. Conclusion The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.


2021 ◽  
Author(s):  
Yusef Ali Syed ◽  
Cecilia Jiang ◽  
Jeffrey Switchenko ◽  
Khadija Kirmani ◽  
Chris Kelsey ◽  
...  

Abstract Background: The role of consolidative radiation therapy (RT) for advanced stage diffuse large B-cell lymphoma (DLBCL) is not fully established. Retrospective data provide evidence for the use of consolidative RT in stage III-IV DLBCL and emerging data from randomized studies address the role of RT in bulky disease for these patients.Methods: Patient with stage III-IV DLBCL treated at two institutions who achieved clinical complete response to systemic therapy were included. Kaplan-Meier analysis was performed to determine the impact of consolidative RT. Univariate and multivariable analyses were performed using a Cox proportional hazards model.Results: One hundred eighty-eight patients received systemic therapy consisting of R-CHOP (79%), another Rituximab-based regimen (9%), or chemotherapy alone (12%). Clinical response was assessed using conventional CT or PET-CT. Sixty-eight patients (36%) received consolidative RT (median dose 30 Gy). Consolidative RT conferred a 36.7% absolute benefit in five-year progression-free survival (85.9% vs. 49.2%, log rank p < 0.0001), and a 14.5% absolute benefit in five-year overall survival (87.4% vs. 72.9%, log rank p = 0.0134). On multivariable analysis, consolidative RT was associated with improved PFS (HR 0.23, 95% CI 0.10-0.52, p < 0.001). Patients receiving consolidative RT demonstrated significantly improved PFS for tumors measuring both <5 cm (log rank p = 0.0454) and ³5 cm (log rank p = 0.0003).Conclusions: For patients with stage III-IV DLBCL who achieve clinical complete response after systemic therapy, consolidative RT improves PFS for all patients, including those with non-bulky disease. This benefit persists in the setting of rituximab-based systemic therapy.


2020 ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  

Abstract Introduction Secondary central nervous lymphoma(SCNSL) was defined as lymphoma involvement of both within and outside CNS at initially diagnosis or CNS relapse of a systemic disease. The prognosis of SCNSL was poor and the most appropriate treatment remained unestablished. Methods We conducted a retrospective study addressing the feasibility of R-MIADD regimen which comprised rituximab, high dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, dexamethasone in 19 consecutive SCNSL patients. Results Nineteen SCNSL patients with newly diagnosed CNS lesions were included with median age of 58 years (range 20 to 72 years). Eleven out of 19(57.9%) patients achieved complete remission(CR) and 2(10.5%) patients achieved partial remission by the end of induction treatment, the overall response rate (ORR) was 68.4%. The median follow-up time after the onset of CNS was 11.1 (3.2-35.5) months, the median progression-free survival after CNS was 28.0 months (95% CI: 11.0-44.9), and the median overall survival after CNS were 34.5months, by the time of this report, 8 patients remained CR. Treatment-related deaths was found in only one patient. Conclusions This is the largest series of SCNSL patients in China, and these date underscore the feasibility and efficacy of R-MIADD as induction treatment of SCNSL, further investigation is warranted.


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