High‐dose therapy and autologous stem cell transplantation may only be applicable to selected patients with secondary CNS diffuse large B‐cell lymphoma

Cheah, Chan Yoon; Joske, David; Cull, Gavin; Gilbertson, Michael; Opat, Stephen; Tam, Constantine S.; Wirth, Andrew; Seymour, John F.

doi:10.1111/bjh.14187

Cited by 10 publications

(7 citation statements)

References 12 publications

(15 reference statements)

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“…Retrospective studies and small single-arm phase II trials support the use of AHCT in patients with relapsed/refractory DLBCL or HGBL with CNS involvement; however, many patients are ineligible because of age, comorbidities, poor performance status, or having a chemorefractory disease. 18 , 26 , 37 – 39 Lenalidomide and the Bruton tyrosine kinase inhibitors have limited activity as monotherapies for CNS involvement by aggressive B-cell lymphoma but are being evaluated in combination with chemotherapy and novel agents. 40 – 42 Despite the recent approvals of several new agents in relapsed/refractory DLBCL and HGBL, treatment of CNS involvement remains an unmet need as these agents have largely not been tested in patients with CNS involvement and likely have limited efficacy in this setting.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Fleming

Huang

Dotson

et al. 2022

Therapeutic Advances in Hematology

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Background: The optimal treatment of patients with systemic diffuse large B-cell (DLBCL) or high-grade B-cell (HGBL) lymphomas with synchronous central nervous system (CNS) involvement at diagnosis is not well defined. High-dose methotrexate administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited. Objective: To report our experience with RM-CHOP in patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis. Design: A single-center retrospective analysis. Methods: We identified consecutive patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis who were treated with RM-CHOP from January 2012 to January 2021. Results: Fifty patients were included with a median age of 62 years; 82% had DLBCL ( n = 41) and 18% had HGBL ( n = 9). Treatment with RM-CHOP was followed by consolidative autologous hematopoietic cell transplantation in 14 patients (28%). The complete response (CR) rate following RM-CHOP was 62%. With a median follow-up of 40 months, the median progression-free (PFS) and overall (OS) survivals were 16 and 58 months, and the 2-year PFS and OS were 41% and 57%, respectively. The 2-year cumulative incidence of CNS progression/relapse was 29%. Outcomes were particularly poor in HGBL, with median PFS and OS of 6 and 7 months, compared with median PFS and OS of 22 months and not reached in DLBCL, respectively. The outcomes of patients with relapsed/progressive disease were poor, with only 63% of patients receiving subsequent treatments and only 21% achieving CR to next subsequent treatment. Most patients (58%) with disease relapse/progression had CNS involvement which was associated with very poor outcomes (median OS of 2 months). Conclusion: CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis dictates clinical outcomes and requires more effective treatment options.

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Section: Discussionmentioning

confidence: 99%

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Fleming

Huang

Dotson

et al. 2022

Therapeutic Advances in Hematology

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“…Secondary central nervous system lymphoma (SCNSL), CNS involvement in a patient with prior extracranial lymphoma, is typically an early and catastrophic event 2 . Favourable response rates have been reported using sequential high‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) in small Phase II trials; 3,4 however, in clinical practice many patients are unsuitable for this intensive treatment due to age or comorbidities 5 . Therefore, novel treatment approaches are needed.…”

Section: Characteristic Study Patient Cohort N (%)mentioning

confidence: 99%

Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience

et al. 2020

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Summary Primary and secondary central nervous system lymphomas (PCNSL/SCNSL) are aggressive rare malignancies with dismal outcomes. Encouraging data have emerged from Phase I/II clinical trials treating relapsed/refractory PCNSL/SCNSL with ibrutinib. We analysed 33 patients who received ibrutinib, alone or with other therapies, for PCNSL (n = 9) or SCNSL (n = 24). The objective response rate was 58% (complete response 55%). The median progression‐free survival and overall survival for patients with PCNSL were both 3·1 months; for SCNSL, 10·2 and 11·5 months respectively. Only one invasive fungal infection was observed, despite concurrent or recent use of dexamethasone 8–16 mg daily in 14 patients (42%). Ibrutinib has encouraging activity in these aggressive malignancies.

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“…Rarely, CNS dissemination is already present at initial diagnosis. Unlike the general favorable outcome of patients with primary CNS lymphoma (PCNSL) when treated with high dose methotrexate (HD-MTX), cytarabine and thiothepa [4][5][6][7], CNS relapse of aggressive B-NHL conveys a dismal prognosis [8,9]. Salvage regimens with relapsed PCNSL incorporating thiothepa and high dose chemotherapy followed by autologous stem cell transplantation (ASCT) showed an improved overall survival (OS) for these patients if initially responsive and subsequently eligible for intensive treatment [10,11].…”

Section: Introductionmentioning

confidence: 99%

Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma

Nijland

Jansen

Doorduijn

et al. 2017

Leukemia & Lymphoma

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Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1-8) and 6 (range 0-8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34-56%) and 49% (95%CI 38-60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging.

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High‐dose therapy and autologous stem cell transplantation may only be applicable to selected patients with secondary CNS diffuse large B‐cell lymphoma

Abstract: cells, programmed death receptor ligand 1/ programmed death receptor 1, and soluble CD25 in Sokal high risk chronic myeloid leukemia. PLoS One, 8, e55818.

Cited by 10 publications

References 12 publications

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience

Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma

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