Elevated lactate dehydrogenase levels detected during routine follow-up do not predict relapse in patients with diffuse large B-cell lymphoma who achieve complete remission after primary treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone-like immunochemotherapy

Abstract Background The use of routine surveillance imaging (RSI) for patients in first complete remission (CR1) following front-line rituximab (R) based anthracycline therapy remains controversial. We compared patients with diffuse large B-cell lymphoma (DLBCL) who received an R-CHOP or a similar regimen, obtained a CR and then were followed by either RSI or clinical surveillance (CS) in which scans were only performed for signs or symptoms. Methods Patients from three tertiary care center from 2001-2011, who achieved a CR1 with frontline R-CHOP or similar therapy for DLBCL, and had a minimum follow up of 1 year were analyzed. Patients with HIV-related lymphoma, transformed lymphoma, and post-transplant lymphoproliferative disorders were excluded. Patients with composite lymphoma were included only if the DLBCL component was >50%. Patients were stratified into two groups based on the surveillance strategy employed. Baseline patient characteristics, prognostic features, treatment type, and outcomes were compared. Results 391 patients with DLBCL treated with R-CHOP or similar regimens who obtained CR1 were analyzed. There were 129 patients in the CS group and 262 in the RSI group. Patient characteristics (age, gender, stage, and IPI) were similar in the two groups. The median follow up is 5 years (range 1 – 12). Relapse after CR1 was detected in 26 (20%) of patients in the CS group and 46 (18%) of the RSI group. The median number of images in the CS group was 0 (range 0-14) and 4 (range 1-27) in the RSI group, p<0.0001. The median average number of images per year of follow up in the CS group was 0 (range 0-6) and 1 (range 1-13) in the RSI group, p<0.0001. Relapses were detected through clinical manifestations in 100 % of CS cases versus 43% in RSI cases, p=0.01. The 5 year progression-free survival (PFS) was 76% in the CS group and 82 % in the RSI group (p = 0.31). The 5 year overall survival (OS) was 87% in the CS group and 92 % in the RSI group (p=0.15). The table shows an analysis of OS by IPI and type of surveillance. Conclusions The majority of relapses in patients with DLBCL after achieving CR1 to an R-CHOP or similar regimen occur when signs or symptoms of the disease lead to evaluation and are not detected by RSI. Although asymptomatic relapses are occasionally detected by RSI, in this large cohort of patients neither a PFS nor OS benefit could be demonstrated in favor of RSI. Given the additional cost, radiation exposure and risk of additional procedures, we conclude that the use of RSI in patients with DLBCL in CR1 has limited clinical utility. Disclosures: No relevant conflicts of interest to declare.

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Routine Imaging for Diffuse Large B-Cell Lymphoma in First Complete Remission Does Not Improve Post-Treatment Survival: A Danish–Swedish Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2015.62.0229 ◽

2015 ◽

Vol 33 (34) ◽

pp. 3993-3998 ◽

Cited By ~ 53

Author(s):

Tarec Christoffer El-Galaly ◽

Lasse Hjort Jakobsen ◽

Martin Hutchings ◽

Peter de Nully Brown ◽

Herman Nilsson-Ehle ◽

...

Keyword(s):

Complete Remission ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Population Based ◽

Population Based Study ◽

Large B Cell Lymphoma ◽

Routine Imaging ◽

Large B Cell ◽

First Complete Remission

Purpose Routine imaging for diffuse large B-cell lymphoma (DLBCL) in first complete remission (CR) is controversial and plays a limited role in detecting relapse. This population-based study compared the survival of Danish and Swedish patients with DLBCL for whom traditions for routine imaging have been different. Patients and Methods Patients from the Danish and Swedish lymphoma registries were included according to the following criteria: newly diagnosed DLBCL from 2007 to 2012, age 18 to 65 years, and CR after R-CHOP/CHOEP. Follow-up for Swedish patients included symptom assessment, clinical examinations, and blood tests at 3- to 4-month intervals for 2 years, with longer intervals later in follow-up. Imaging was only recommended when relapse was clinically suspected. Follow-up for Danish patients was similar but included routine imaging (usually computed tomography every 6 months for 2 years). Results Danish (n = 525) and Swedish (n = 696) patients with DLBCL had comparable baseline characteristics. Cumulative 2-year progression rate after CR was 6% (95% CI, 4 to 9) for International Prognostic Index (IPI) ≤ 2 versus 21% (95% CI, 13 to 28) for IPI > 2. Age > 60 years (hazard ratio [HR], 2.3; 95% CI, 1.6 to 3.4), elevated lactate dehydrogenase (HR, 2.3; 95% CI, 1.4 to 3.8), B symptoms (HR, 1.7; 95% CI, 1.1 to 2.5), and Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 1.8; 95% CI, 1.0 to 3.0) were associated with worse post-CR survival. Imaging-based follow-up strategy had no impact on survival, neither for all patients nor for IPI-specific subgroups. Conclusion DLBCL relapse after first CR is infrequent, and the widespread use of routine imaging in Denmark did not translate into better survival. This favors follow-up without routine imaging and, more generally, a shift of focus from relapse detection to improved survivorship.

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Prospective Management of Primary Testicular Lymphoma (PTL) with Doxorubicin-Based Chemotherapy, Prophylactic Intrathecal (IT) Methotrexate and Radiotherapy (RT), but without Rituximab: Results from IELSG.

Blood ◽

10.1182/blood.v108.11.2454.2454 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2454-2454 ◽

Cited By ~ 1

Author(s):

Andreas H. Sarris ◽

Umberto Vitolo ◽

Emanuele Zucca ◽

George Z. Rassidakis ◽

Jeffrey Medeiros ◽

...

Keyword(s):

Complete Remission ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Contralateral Testis ◽

Large B Cell Lymphoma ◽

Frequent Relapses ◽

Large B Cell

Abstract Introduction: PTL is a rare extranodal lymphoma characterized by a continuous pattern of systemic relapses in spite of doxorubicin-based therapy. There are also frequent relapses in the contralateral testis and the central nervous system (CNS). Therefore we decided to determine whether prophylaxis of the CNS and the contralateral testis would modify the pattern of relapse of PTL. Patients and methods: From 1993 to February 2002 in IELSG member institutions patients with PTL (presenting with testicular enlargement) were managed with doxorubicin-based therapy according to institutional policy, with the addition of four doses of IT methotrexate (15 mg) during the first 6 weeks. At the end of chemotherapy scrotal RT (30 Gy) was given to all patients and 30–36 Gy nodal RT to those with stage II disease. Rituximab was not used in this cohort because it was not yet generally available for patients with diffuse large B-cell lymphoma. Results: There were twenty seven patients; two refused chemotherapy and/or RT/IT therapy and one RT, leaving 24 eligible for analysis. Median age was 60 years (range 31–80). Ann Arbor stage was I in 17, II in four, and four in three patients. B-symptoms were present in one patient. The right testis was involved in 13 and the left in 11 patients. Serum LDH was elevated in four of 21 with available values. No patient had CNS involvement at diagnosis. Pathology was diffuse large B-cell lymphoma in all patients. Treatment was CHOP in 21, alternating triple therapy in two, and hyper-CVAD in one patient. Three patients died during therapy: one from neutropenic sepsis and two from toxicity of systemic methotrexate. The remaining 21 patients achieved a complete remission. With a median follow-up of 57 months (range 8–123) for survivors, seven patients have relapsed, three in the CNS. There were no testicular relapses. Eight patients have died: three from toxicity during induction, three from relapsed lymphoma, one from gastric carcinoma and one from sudden death, both in complete remission. At 5 years the projected progression-free survival was 78%, and survival 66%, but both without an apparent plateau. Freedom from progression in the CNS was 84%, with a plateau. Conclusions: Patients with PTL treated prospectively with doxorubicin-based therapy before the availability of rituximab exhibit the continuous pattern of relapse previously reported. Scrotal RT seems eliminate testicular relapses, and prophylactic IT methotrexate seems to reduce, but not eliminated CNS relapses. These need to be confirmed by longer follow-up. The ongoing IELSG-10 should determine whether the addition of rituximab alters the continuous pattern of systemic relapses. Future studies should determine the molecular basis of the continuous relapses and minimize both systemic and CNS relapses.

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Safety and Efficacy of Rituximab Plus Bendamustine in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Patients

Blood ◽

10.1182/blood.v124.21.3074.3074 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3074-3074 ◽

Cited By ~ 1

Author(s):

Annalisa Arcari ◽

Annalisa Chiappella ◽

Vanessa Valenti ◽

Luca Zanlari ◽

Monica Tani ◽

...

Keyword(s):

Complete Remission ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Extranodal Involvement ◽

Large B Cell Lymphoma ◽

Stage Disease ◽

Poor Functional Status ◽

Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) relapsed or refractory after chemoimmunotherapy have dismal prognosis; the standard salvage treatment is Rituximab plus high dose chemotherapy with autologous stem cell transplantation (R-HDC). However, no standardized treatment is available for patients not eligible for R-HDC because of age and/or comorbidity. The combination Rituximab plus Bendamustine (R-B) has shown to be non-inferior and with a favorable toxicity profile compared to R-CHOP in indolent B-cell lymphoma. The use of R-B in DLBCL is a matter of debate. Purpose: We designed an Italian multicenter retrospective study aimed to evaluate safety and efficacy of R-B as salvage treatment in patients with DLBCL relapsed or refractory after at least one complete course of Rituximab-chemotherapy, who were not eligible for R-HDC because of age and/or comorbidity or in patients with post-HDC recurrence. Patients and Methods: We retrospectively reported 43 unselected consecutive patients with relapsed or refractory DLCBL treated with R-B in 15 Italian haematological centers between October 2008 and January 2014. Schedule of R-B were: 6 courses of Bendamustine at 90 mg/mq or 70 mg/mq on days 1 and 2 of each 28-day cycle and Rituximab 375 mg/mq on day 1 of each cycle. They were analyzed for baseline characteristics (age, IPI, ECOG, comorbidity), outcome (ORR, PFS, OS) and toxicity (CTCAE). Results: The median age was 76 years (range 56-94). Eighty-three % of patients had advanced-stage disease (III-IV stage) and 67% had IPI score of ≥3. An extranodal involvement was present in 65% of cases (bone marrow, lung, stomach, skin, pleura, pericardium). More than half the patients (51%) presented with poor functional status with ECOG score of ≥2. Comorbidity assessment by CIRS-G revelead 30% of patients with ≥1 severely or very severely (level 3 or 4) affected organs and 27% of patients with moderate or severe (level ≥2) cardiopathy. The mean number of prior therapies was 1,7 (range 1-3). All patients were previously treated with Rituximab-chemotherapy and three patients had already received R-HDC. Twelve patients had a refractory disease and 31 experienced relapse after last treatment. Patients received a median of 5 cycles of planned 6 courses of R-B (range 2-6); 24 patients underwent Bendamustine at 90 mg/mq, 19 at 70 mg/mq. All patients received Rituximab 375 mg/mq. In 38% of patients treatment was stopped because of progression; in 4 patients (9%) progression occurred within the first 2 treatment cycles. The overall response rate was 47%, including 28% complete remission and 19% partial remission. One patient in partial remission after R-B achieved a complete remission after local radiotherapy. The median OS was 16 months (95% CI 10-20). The median PFS was 8 months (95% CI 6-11). The median follow up was 10 months (range 2-60). Nine patients are still alive and in complete remission at last follow up; 7 of these patients had a chemosensitive relapse before R-B (in 5 cases a first relapse) and only 2 had a refractory disease with progression after a previous lenalidomide treatment. Toxicity was moderate, mainly grade 1 and 2. Grade 3-4 adverse events were neutropenia in 14 patients (32%), thrombocytopenia in 5 patients (11%), anemia in one patient, infections in 3 patients (6%), skin rash in one patient, nausea in one patient, diarrhea in one patient. One patient died of septic shock after the third R-B cycle. One patient died of miocardial infarction related to underlying cardiac comorbidity. Conclusions: Bendamustine in combination with Rituximab showed promising efficacy results with a low toxicity profile in a poor prognosis population (advanced stage disease and extranodal involvement, high median age, poor functional status, comorbidities), not eligible for R-HDC. The optimal dosage and schedule of Bendamustine and/or combination with novel drugs should be further investigated, in order to improve the duration of response and reduce the rate of early progression. Disclosures Off Label Use: Bendamustine in diffuse large B-cell lymphoma. Marasca:Mundipharma: Honoraria.

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Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP-BLEO regimens

European Journal Of Haematology ◽

10.1034/j.1600-0609.2001.00272.x ◽

2001 ◽

Vol 66 (2) ◽

pp. 94-99 ◽

Cited By ~ 12

Author(s):

Agustin Aviles ◽

Sergio Cleto ◽

Judith Huerta-Guzman ◽

Natividad Neri

Keyword(s):

Complete Remission ◽

Maintenance Therapy ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Interferon Alfa ◽

Poor Risk ◽

Large B Cell Lymphoma ◽

Large B Cell

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Primary Extra-Nodal DLBCL of Glands: Our Experiences outside Guidelines of Treatment

Healthcare ◽

10.3390/healthcare9030286 ◽

2021 ◽

Vol 9 (3) ◽

pp. 286

Author(s):

Antonello Sica ◽

Mario Santagata ◽

Caterina Sagnelli ◽

Piero Rambaldi ◽

Renato Franco ◽

...

Keyword(s):

Lymph Node ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoid Tissues ◽

Clinical Recovery ◽

Large B Cell Lymphoma ◽

Thyroid Glands ◽

Chemotherapy Protocol ◽

Large B Cell

Lymphomas usually involve lymph nodes and other lymphoid tissues, but sometimes occur in non-lymphoid organs, called extra-nodal sites. Primary diffuse extra-lymph node large B-cell lymphoma (DLBCL) of the thyroid and parotid gland have been observed rarely. According to the most accredited guidelines, primary extra-nodal DLBCL of the parotid and thyroid glands should be treated with three cycles of R-CHOP followed by radiotherapy of the involved site (ISRT). Surgery alone is not enough to treat DLBCL. We describe two unusual cases of primary extra-nodal DLBCL in elderly patients treated exclusively with surgical resection, given the inability to apply chemotherapy. Both patients achieved clinical recovery, which was maintained after a follow-up of more than 18 months, despite not having performed the indicated chemotherapy protocol. The two cases presented here, and a few others reported in the literature, should be considered exceptions to the rule, and do not allow the conclusion that surgery alone might be sufficient for complete remission.

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CT-based radiomics model with machine learning for predicting primary treatment failure in diffuse large B-cell Lymphoma

Translational Oncology ◽

10.1016/j.tranon.2021.101188 ◽

2021 ◽

Vol 14 (10) ◽

pp. 101188

Author(s):

Raoul Santiago ◽

Johanna Ortiz Jimenez ◽

Reza Forghani ◽

Nikesh Muthukrishnan ◽

Olivier Del Corpo ◽

...

Keyword(s):

Machine Learning ◽

Treatment Failure ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Primary Treatment ◽

Large B Cell Lymphoma ◽

Large B Cell

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Nivolumab plus gemcitabine, dexamethasone, and cisplatin chemotherapy induce durable complete remission in relapsed/refractory primary mediastinal B-cell lymphoma: a case report and literature review

Journal of International Medical Research ◽

10.1177/0300060520945075 ◽

2020 ◽

Vol 48 (8) ◽

pp. 030006052094507

Author(s):

Gang Huang ◽

Ju Huang ◽

Zhili Zhang ◽

Chongchong Xue ◽

Yuan Liu

Keyword(s):

Complete Remission ◽

B Cell ◽

Cell Lymphoma ◽

Combined Therapy ◽

B Cell Lymphoma ◽

Immune Checkpoint Blockade ◽

Large B Cell Lymphoma ◽

Clinical Trial Designs ◽

Potential Use ◽

Large B Cell

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, but aggressive, type of B-cell lymphoma. Patients with relapsed refractory PMBCL (rrPMBCL) have limited therapeutic options and usually have a relatively poor outcome. Immune checkpoint blockade has become a potential treatment for this disease. We report here a case of a female patient with rrPMBCL who was treated with nivolumab plus gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. Complete remission was achieved after four cycles of combined therapy. With continued nivolumab maintenance monotherapy, she has remained in complete remission for longer than 28 months. This is the first report of nivolumab plus GDP chemotherapy inducing complete remission in patient with rrPMBCL. This case supplements the limited literature and provides implications for clinical trial designs regarding the potential use of nivolumab in the treatment of rrPMBCL.

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C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

Asian Pacific Journal of Cancer Biology ◽

10.31557/apjcb.2021.6.1.15-20 ◽

2021 ◽

Vol 6 (1) ◽

pp. 15-20

Author(s):

Mahmoud Tag El-Hussien ◽

Nadia Mokhtar ◽

Eman Naguib Khorshed

Keyword(s):

Protein Expression ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Statistical Prediction ◽

Proliferative Index ◽

Ki 67 ◽

Large B Cell Lymphoma ◽

Large B Cell

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

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