Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era

Kumar, Anita; Lunning, Matthew A.; Zhang, Zhigang; Migliacci, Jocelyn; Moskowitz, Craig H.; Zelenetz, Andrew D.

doi:10.1111/bjh.13766

Cited by 33 publications

(18 citation statements)

References 29 publications

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“…22 The current study is the first multicenter analysis to focus specifically on LS-DLBCL/HGBL with MYC-R and/or BCL2-R and/or BCL6-R within 1 radiation field. Although the 2-year PFS and OS in our cohort (78% and 86%, respectively) were lower than historical cohorts of LS-DLBCL, 23,24 they are significantly better than previous reports that included patients with advanced-stage MYC-R DLBCL/HGBL and DHL. 17,19 We excluded LS patients with MYC-R with disease outside of 1 radiation field to limit heterogeneity of disease, minimize bias that could be involved in frontline therapy selection (ie, treating physician may tend to use IIC in stage 2 disease outside of 1 radiation field with adverse cytogenetics), and allow direct comparison of patients treated with and without radiation therapy.…”

Section: Discussioncontrasting

confidence: 86%

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics

et al. 2020

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There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.

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Section: Discussioncontrasting

confidence: 86%

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics

et al. 2020

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“…21 It was recently reported that in contrast to advanced stage DLBCL, the cell-of-origin is not prognostic in limited stage disease. 9,13 To impact prognosis of these good risk patients, a biomarker, such as MYC breaks, might be helpful. 12 We found an MYC translocation in 3 of 11 evaluable relapsed cases.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the generally favourable outcome, relapses still occur in 10 to 20% of patients with limited stage DLBCL and 5-year OS ranges between 75% and 94%, which suggests that salvage of relapses is frequently unsuccessful. [6][7][8][9][10] Clinical prognostic models only partially identify patients at risk for relapse. 2,11 Biological tumour characteristics such as cell of origin and especially presence of MYC translocation have prognostic significance in DLBCL.…”

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confidence: 99%

Relapse in stage I(E) diffuse large B‐cell lymphoma

Nijland

Boslooper

Imhoff

et al. 2017

Hematological Oncology

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Despite a general favourable outcome in limited stage diffuse large B‐cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow‐up of 53 months (range 5‐132 months), 1 progressive disease and 18 relapses occurred. The 5‐year time to tumour progression and disease‐specific survival were 85% (95% CI 79‐91%) and 92% (95% CI 87%‐97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease‐specific survival between patients treated with abbreviated R‐CHOP plus involved field radiotherapy or with 6 to 8 cycles of R‐CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.

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“…These biologic features may affect the selection of CNS prophylaxis in primary breast DLBCL patients. Given the recent retrospective data that appropriately selected limited-stage DLBCL (i.e., completely resected or interim PET-negative lymphomas) might be successfully treated with short-course immunochemotherapy without radiotherapy [25,26], a large subgroup of patients who did not have any biologic features for poor clinical outcomes might have excellent outcomes with a low risk for CNS failure. These patients may be eligible for study with de-escalating treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

First-Line Treatment for Primary Breast Diffuse Large B-Cell Lymphoma Using Immunochemotherapy and Central Nervous System Prophylaxis: A Multicenter Phase 2 Trial

Yhim

Yoon

Kim

et al. 2020

Cancers

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There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.

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Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era

Cited by 33 publications

References 29 publications

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics

Relapse in stage I(E) diffuse large B‐cell lymphoma

First-Line Treatment for Primary Breast Diffuse Large B-Cell Lymphoma Using Immunochemotherapy and Central Nervous System Prophylaxis: A Multicenter Phase 2 Trial

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