Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by The Nordic Lymphoma Group

Pulczynski, Elisa Jacobsen; Kuittinen, Outi; Erlanson, Martin; Hagberg, Hans; Fosså, Alexander; Eriksson, Mikael; Nordström, Marie; Østenstad, Bjørn; Fluge, Øystein; Leppä, Sirpa; Fiirgaard, B; Bersvendsen, Hanne Skjerven; Fagerli, Unn Merete

doi:10.3324/haematol.2014.108472

Cited by 92 publications

(74 citation statements)

References 31 publications

(48 reference statements)

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“…Based on a recent systematic review, 7 only few prospective multicentre studies focussing on elderly patients with PCNSL have been reported, 14, 15, 16, 17, 18, 19, 20 which all used HD-MTX-based chemotherapy. However, no standard protocol has yet been defined and there was no study that used rituximab.…”

Section: Discussionmentioning

confidence: 99%

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

et al. 2016

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To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2–11) and lomustine (110 mg/m2, day 2)—R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3% R-MP 34.9% R-MPL 38.8%) and overall survival (All 47.0% R-MP 47.7% R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

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Section: Discussionmentioning

confidence: 99%

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

et al. 2016

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“…[10][11][12]19,22 In a multicentre retrospective analysis investigating patients with a median age of 52.4 years undergoing HDT-ASCT as salvage therapy, the 5-year survival rate of patients with chemosensitive relapse was 62%. 13 In another large retrospective analysis investigating patients with a median age of 54 years undergoing HDT-ASCT as first-line treatment, the reported 2-and 5-year survival rates were 82% and 79%, respectively.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

“…Based on a recent systematic review, 9 a limited number of prospective multicentre studies focussing on elderly PCNSL patients has been reported. 8,[17][18][19][20][21] Most of the studies included HD-MTX in combination with partner chemotherapy agents, but to-date no standard protocol has been defined. Acknowledging the limitations of intertrial comparison, the best reported response rate was 79% but the corresponding 1-year PFS was only 36%.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study

Schorb

Fox

Fritsch

et al. 2017

Bone Marrow Transplant

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In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.

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“…Nine of the 14 studies dedicated to elderly patients [7, 12, 25, 26, 28-32] were retrospective, and 4 were phase II studies [4, 5, 9, 27], with one of them designed as a randomized phase II study [4]. Six studies that reported on elderly subgroups were phase II studies [6, 14-16, 34, 35], and 1 was a retrospective analysis of elderly patients in a phase III study [13]. Treatment regimens varied from monotherapy to multidrug HD-MTX-based combinations.…”

Section: Diagnosis and Treatment Of Elderly Patients With Pcnslmentioning

confidence: 99%

“…Fourteen studies were dedicated to elderly patients [4, 5, 7, 9, 12, 24-33], and 7 studies accrued adult patients of all ages but contained information on outcome of the elderly subgroup [6, 13-16, 34, 35]. One retrospective study [3] described the outcome of thiotepa-based chemotherapy with ASCT administered to 52 elderly lymphoma patients, of whom 15 were PCNSL treated by this protocol as first-line approach.…”

Section: Diagnosis and Treatment Of Elderly Patients With Pcnslmentioning

confidence: 99%

Primary CNS Lymphoma in the Elderly: The Challenge

Siegal

Bairey

2019

Acta Haematol

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Primary central nervous system (CNS) lymphoma is an aggressive brain tumor sensitive to chemotherapy and radiotherapy. Its incidence has increased in the elderly, and they account for the majority of patients. The median survival of patients older than 70 years did not change over the last 40 years and remained in the range of 6–7 months. The definition of elderly is nonuniform, and chronological age is not the best marker of treatment tolerability or a predictor of treatment-related toxicity. Some patients who are fit can tolerate induction, consolidation, and even high-dose chemotherapy with autologous stem cell transplantation, whereas others who have multiple comorbidities with reduced renal and bone marrow function can tolerate only intermediate doses of methotrexate. The latter may benefit from maintenance treatment. The “elderly” are also susceptible to the accelerated and detrimental cognitive side effects of whole-brain irradiation which is an alternative consolidation to high-dose chemotherapy. The optimal treatment remains an unresolved matter. A comprehensive comorbidity and geriatric assessment is imperative for appraisal of treatment-induced risks for CNS and systemic toxicity. An individualized approach is required aiming to prolong survival while minimizing toxicity. Future studies should assess the potential of new agents for improving outcome and maintaining quality of life.

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Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by The Nordic Lymphoma Group

Abstract: lymphomas (DLBCL) and it was previously shown that the addition of rituximab to CHOP chemotherapy has improved the prognosis in DLBCL outside the brain. 8 2) The intraventricular MTX/cytarabine treatment of the Bonn protocol requiring an Ommaya reservoir was

Cited by 92 publications

References 31 publications

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study

Primary CNS Lymphoma in the Elderly: The Challenge

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