Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era

Bobillo, Sabela; Joffe, Erel; Lavery, Jessica A.; Sermer, David; Ghione, Paola; Noy, Ariela; Caron, Philip; Hamilton, Audrey; Hamlin, Paul A.; Horwitz, Steven M.; Kumar, Anita; Matasar, Matthew J.; Moskowitz, Alison J.; Owens, Collette N.; Palomba, M. Lia; Batlevi, Connie Lee; Straus, David J.; Keudell, Gottfried von; Zelenetz, Andrew D.; Yahalom, Joachim; Doğan, Ahmet; Seshan, Venkatraman; Younes, Anas

doi:10.1182/blood.2020005112

Cited by 45 publications

(41 citation statements)

References 28 publications

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“…Our study observed that, among 289 patients, the 4-year PFS and OS rates were 90.3 and 94.1%, respectively, much higher than those in patients receiving chemotherapy alone (24). Besides that, extranodal involvement showed no obvious influence on either PFS or OS in localized DLBCL, which seems contradictory with a previous report that addressed the inferior survival of extranodal disease (9). This may be attributed to the different study enrollments between two studies.…”

Section: Discussioncontrasting

confidence: 99%

“…This may be attributed to the different study enrollments between two studies. Moreover, compared with the previous study ( 9 ), our study included more SE patients with GI tract involvement that was related to favorable outcomes but less SE patients with bone involvement that was related to unfavorable outcomes ( 17 ). As reported in DLBCL ( 25 ), serum LDH was also recognized as an unfavorable prognostic factor in localized DLBCL, indicating that more potentially effective immunochemotherapy regimen should be applied in this subset of localized DLBCL patients to improve their outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Other than lymph node, Waldeyer's ring and spleen are considered as nodal tissue ( 8 ), while GI tract, breast, and CNS are the most common extranodal sites. More recently, extranodal involvement has been identified as an important prognostic factor for inferior survival in localized DLBCL ( 9 ), suggesting the potential heterogeneity between nodal and extranodal involvement. Distinct gene mutations have been related to specific extranodal sites of DLBCL.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Heterogeneity in Localized Diffuse Large B-Cell Lymphoma

Qin

Shi

et al. 2021

Front. Oncol.

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The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network–International Prognostic Index. According to the molecular features, increased MPEG1 mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-β signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase >3 upper limit of normal was an independent adverse prognostic factor for OS, and ATM mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular Heterogeneity in Localized Diffuse Large B-Cell Lymphoma

Qin

Shi

et al. 2021

Front. Oncol.

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“…This was mostly observed in patients with advanced disease [8,10,28]. More recent studies suggest that radiotherapy might be omitted in PET-negative patients [41,42]. It is noteworthy that it was difficult to precisely analyze the impact of radiotherapy in our cohort, as some patients received radiotherapy early during treatment and some as consolidation therapy.…”

Section: Discussionmentioning

confidence: 93%

Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Mercier

Orvain

Rochelle

et al. 2021

Cancers

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Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

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“…By analyzing tumor reservoirs persisting after treatment, they also show that clonal selection-induced resistance results from a different mechanism in HR patients. 1 In MM, patients displaying HR cytogenetic features have similar levels of complete response as standard-risk (SR) patients, but shorter progression-free survival (PFS) and overall survival (OS), which is why response duration is more important than the depth of response. 2 However, thanks to the recent MRD revolution, it is possible to evaluate the response to treatment with unprecedented sensitivity; consequently, it is possible to better identify patients who will progress soon among those in a conventional complete response.…”

Section: Undetectable Mrd Can Change the Dealmentioning

confidence: 99%

Stage I DLBCL: extranodal may mean extra radiation

Lossos

2021

Blood

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In this issue of Blood, Bobillo et al 1 present a retrospective analysis of outcomes in stage I diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens with or without radiation therapy (RT). While the overall outcome was excellent, patients with extranodal presentation had an inferior outcome compared with patients with nodal disease. Consolidation with RT improved progression-free survival (PFS) and overall survival (OS) in patients with extranodal disease, mainly due to improved outcomes in positron emission tomography (PET)-positive patients at the end of immunochemotherapy.Limited-stage presentation accounts for ;30% to 40% of DLBCL cases. Retrospective analyses and clinical trials in these patients demonstrated favorable but markedly variable outcomes following short-or full-course chemotherapy with or without rituximab with or without RT. Variability in outcomes in limited-stage DLBCL patients stems from different definitions of limited stage (stage I or both stage I and II), tumor bulk, and whether staging was performed by PET computed tomography. Differences in survival can also be attributed to the presence of unfavorable clinical characteristics that constitute the stage-modified International Prognostic Index (sm-IPI) 2 (age .60 years, elevated lactate dehydrogenase, performance status $2, and stage II), bulky disease, and biological heterogeneity. While extranodal involvement, a risk factor in the original IPI, is not included in the sm-IPI, there are reports suggesting that extranodal presentation may be associated with inferior outcomes. 3

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Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era

Cited by 45 publications

References 28 publications

Molecular Heterogeneity in Localized Diffuse Large B-Cell Lymphoma

Molecular Heterogeneity in Localized Diffuse Large B-Cell Lymphoma

Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Stage I DLBCL: extranodal may mean extra radiation

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