Prognostic factors, therapeutic approaches, and distinct immunobiologic features in patients with primary mediastinal large B-cell lymphoma on long-term follow-up

Abstract Introduction: Patients with limited stage aggressive B-cell non-Hodgkin lymphoma (LS-NHL) and at least one stage-modified adverse risk factor have an excessive relapse rate leading to a 5-year overall survival (OS) of 50-77% and 10-year OS of 0-50%. In SWOG S0014 we have shown that the addition of rituximab to 3 cycles of CHOP plus involved field radiation therapy (IFRT) resulted in an improved estimated 4-year progression-free survival (PFS) of 88% and OS of 92%. Relapses were largely systemic (5 of 6 evaluable) and continued to be seen with longer follow-up. Ibritumomab tiuxetan (Zevalin ®) is a radiolabeled anti-CD20 antibody that has excellent single agent activity in diffuse large B-cell lymphoma and could prevent systemic relapse of disease. We now report long term results of SWOG S0313, a phase II study of ibritumomab tiuxetan consolidation after 3 cycles of CHOP plus IFRT in patients with LS-NHL. Methods: Patients with LS-NHL and at least one stage-modified adverse risk factor (non-bulky stage II, age > 60 years, elevated LDH, or WHO performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40-50 Gy of IFRT. Ibritumomab tiuxetan regimen was initiated 3 – 6 weeks following IFRT. Results: Forty-six patients were registered and eligible, with median follow-up of 7.3 years. Median age was 61, 37% of patients had elevated LDH, and 20% had systemic symptoms. Grade 4 adverse events occurring more than once included neutropenia (8 patients), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. Eleven patients progressed and 8 patients died. The PFS estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. OS estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. These outcomes compare favorably to matched cohorts on prior SWOG trials, with 7-year PFS estimate of 68% on S0014 and 65% on S8736 (original pre-Rituximab trial); and 7-year OS estimate of 80% on S0014 and 73% on S8736 cohorts. Conclusions: Patients with high-risk LS-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. A US cooperative group study of R-CHOP and response-adapted IFRT followed by consolidative ibritumomab tiuxetan is ongoing. Disclosures Off Label Use: ibritumomab tiuxetan in diffuse large B-cell lymphoma.

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Faculty Opinions recommendation of Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725283014.793521324 ◽

2016 ◽

Author(s):

Won Seog Kim

Keyword(s):

Poor Prognosis ◽

Phase Ii Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Long Term Follow Up ◽

Large B Cell ◽

Patients With Poor Prognosis

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Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients With Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'Adulte

Journal of Clinical Oncology ◽

10.1200/jco.2005.09.131 ◽

2005 ◽

Vol 23 (18) ◽

pp. 4117-4126 ◽

Cited By ~ 989

Author(s):

P. Feugier ◽

A. Van Hoof ◽

C. Sebban ◽

P. Solal-Celigny ◽

R. Bouabdallah ◽

...

Keyword(s):

Elderly Patients ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Long Term Results ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

Purpose To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. Patients and Methods LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m2 was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. Results Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. Conclusion Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.

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Outcome of Patients with Primary Mediastinal Large B-Cell Non-Hodgkin’s Lymphomas: A Single Institution Analysis from 1996-2004.

Blood ◽

10.1182/blood.v104.11.3302.3302 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3302-3302

Author(s):

Ute Hegenbart ◽

Michael Rieger ◽

Matthias Witzens ◽

Manfred Hensel ◽

Anthony D. Ho

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

First Line ◽

Large B Cell Lymphoma ◽

Autologous Hct ◽

Line Chemotherapy ◽

Large B Cell

Abstract Primary mediastinal large B-cell lymphoma represents a distinct subset of large B cell lymphoma, and it has been shown to occur preferentially in young females with a bulky mediastinal mass. Between 1996 and 2004, a total of 43 patients (pts) with primary mediastinal lymphoma were diagnosed and treated at our institution, 34 of them are evaluable for response and long-term follow-up. Twenty females and 14 males have been treated, the median age at diagnosis was 33 years (range: 18–56), 10 pts had stage I, 19 pts stage II and 5 pts stage III disease, respectively. Fifteen pts presented with B symptoms, LDH was increased in 68% of pts. First-line chemotherapy included CHOP (2 pts), R-CHOP (3 pts), CHOEP (8 pts), R-CHOEP (13 pts) or Mega-CHOEP (8 pts). 16 pts received Rituximab in combination with chemotherapy as front-line therapy. Complete response after first-line therapy has been observed in 71% and PR in 21% of pts. Later on, two pts in CR and 1 pt with PR relapsed after conventional chemotherapy. Radiotherapy was administered in 22 pts (65%) presenting with initial bulky disease. 19 pts have been autografted, 15 of them as part of up-front therapy. Indications for up-front autologous HCT were treatment within the Mega-CHOEP protocol (n=8), PR after first-line chemotherapy (n=3), IPI Score of 2 (n=2) and individual decision in 2 pts. Allogeneic HCT was performed as relapse therapy in 4 patients. Of the 15 pts who had up-front autologous HCT, 13 remained in CR. Overall, thirty pts were alive at the date of last contact with a median follow-up since diagnosis of 25 months (range 3–99). Three of 4 pts who had undergone allogeneic HCT in a advanced phase of disease died of transplant-related complications. In conclusion, in this patient group addition of Rituximab and/or dose-intensified first-line chemotherapy lead to a high rate of complete remissions as compared to historic controls. Whether up-front high-dose chemotherapy with autologous HCT or the administration of radiotherapy to the initial bulk improve PFS and OS remains an open question for this special lymphoma entity. The achievement of complete remission with primary treatment strategies seems to be essential to achieve long-term cure for this disease.

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Long term follow-up (FU) of lenalidomide plus R-CHOP therapy in patients with newly diagnosed diffuse large b-cell lymphoma (DLBCL): Combined analysis from two phase 2 trials.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.7562 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 7562-7562 ◽

Cited By ~ 1

Author(s):

Alessia Castellino ◽

Betsy LaPlant ◽

Levi Pederson ◽

Annalisa Chiappella ◽

Gianluca Gaidano ◽

...

Keyword(s):

Cell Lymphoma ◽

B Cell Lymphoma ◽

Phase 2 ◽

Newly Diagnosed ◽

Two Phase ◽

Large B Cell Lymphoma ◽

Long Term Follow Up ◽

Large B Cell

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Long-Term Follow-Up of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: Aims and Methodological Approach for Fondazione Italiana Linfomi Systematic Reviews

Cancers ◽

10.3390/cancers13122976 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2976

Author(s):

Chiara Gerardi ◽

Eleonora Allocati ◽

Carla Minoia ◽

Attilio Guarini ◽

Rita Banzi

Keyword(s):

B Cell ◽

Systematic Reviews ◽

Hematological Malignancies ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Classical Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Advances in diagnosis and treatment of hematological malignancies has boosted attention on optimal follow-up care of survivors after cancer. To collect evidence that could inform the development of an optimal model for Italian hematology centers and the scientific community, Fondazione Italiana Linfomi (FIL) commissioned an analysis of the international follow-up approaches for long-term survivors after classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL). FIL set up multidisciplinary teams, representing all different skills relevant for cancer survivors. They conducted a series of systematic reviews focused on three main aspects: incidence of long-term toxicity; comparison of old or standard therapies and more recent ones; and evidence on specific follow-up approaches. The teams applied this framework to cardiological, endocrine-metabolic, neurological/cognitive, and psychological disorders, secondary cancers, fertility preservation, and lifestyles. Each team conducted comprehensive literature searches on PubMed, Embase and Cochrane Library databases up to 2020. Screening followed the PRISMA statement for reporting systematic reviews. The reviews report the results of this wide project covering the main areas of late toxicity and conditions in the long-term survival of cHL and DLBCL patients and their follow-up. From a clinical point of view, the series confirmed that the evidence on follow-up tended to focus on solid tumors with scant evidence on hematological malignancies.

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