High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study

Schorb, Elisabeth; Kasenda, Benjamin; Ihorst, Gabriele; Scherer, Florian; Wendler, Julia; Isbell, Lisa K; Fricker, Heidi; Finke, Juergen; Illerhaus, Gerald

doi:10.1182/bloodadvances.2020002064

Cited by 39 publications

(43 citation statements)

References 25 publications

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“…Only recently was this method of consolidation prospectively explored in a population that included patients >70 years of age. Schorb et al reported that HDC-ASCT with busulfan/thiotepa conditioning was feasible and well tolerated in a carefully selected group of fourteen patients with a median age of 74 (range, 69–79) with no treatment related deaths ( 49 ). However only 40% of screened patients met eligibility for enrollment, highlighting the fact that there is a subset of patients, predominantly the elderly, for whom HDC-ASCT is not an option and whom are high risk for neurotoxicity with WBRT.…”

Section: Consolidation Therapymentioning

confidence: 99%

Primary central nervous system lymphoma: a narrative review of ongoing clinical trials and goals for future studies

Schaff¹,

Ambady²,

Doolittle³

et al. 2021

Ann Lymphoma

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Primary central nervous system lymphoma (PCNSL) is a rare disease of the brain, spine, cerebrospinal fluid (CSF) and/or vitreoretinal space. PCNSL is chemo and radiosensitive but relapse is common even years after initial treatment. Outside of consensus regarding the use of high-dose methotrexate (HD-MTX) for first line treatment, there is little uniformity in the management of newly diagnosed or relapsed PCNSL. The lack of consensus is driven by a paucity of randomized trials in this disease. Prospective studies are troubled by low enrollment, the lack of a standard induction regimen, and a varied approach to consolidation strategies. Moreover, the PCNSL patient population is heterogeneous and includes a high proportion of elderly or frail patients and consists of patients manifesting disease in varied compartments of the central nervous system (CNS). As a result, current treatment strategies vary widely and are often dictated by physician and institutional preference or regional practice. This review provides an overview of recently completed and ongoing therapeutic studies for patients with newly diagnosed and recurrent or refractory PCNSL. It discusses the existing evidence behind common approaches to induction and consolidation or maintenance regimens as well as the recent data regarding management of recurrent disease. Finally, it highlights the complexity of trial design in this disease and provides a framework for the design of future studies, which are needed to identify patient populations likely to benefit from specific induction, consolidation, or maintenance therapies.

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Section: Consolidation Therapymentioning

confidence: 99%

Primary central nervous system lymphoma: a narrative review of ongoing clinical trials and goals for future studies

Schaff¹,

Ambady²,

Doolittle³

et al. 2021

Ann Lymphoma

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“…The studies were published between 1992 and 2020. Only eight out of 26 studies were specifically designed for elderly patients with an age cut-off of 60 years or older [31,[55][56][57][58][59][60][61]. The remaining studies included patients with a wider age range and also provided individual patient data or subgroup data for elderly patients.…”

Section: Key Characteristics Of Prospective Non-randomized Studiesmentioning

confidence: 99%

Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Schorb

Isbell

Illerhaus

et al. 2021

Cancers

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Background: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. Materials and Methods: We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. Results: In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Conclusions: Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment.

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“…Nevertheless, this approach is still very scarce. In a pilot study, Schorb et al have utilized the Cumulative Illness Rating Scale–Geriatric score as an inclusion criterion in addition to age [ 24 ]. Such approaches should be developed.…”

Section: Clinical Aspectsmentioning

confidence: 99%

“…In randomized trials, this strategy has been shown to be an alternative option to WBRT as consolidation, with a better preservation of neurocognitive functions at least in the short-term follow-up, but at the price of an expected important systemic toxicity and a toxic death rate of 5–10%. While this strategy has been classically reserved for younger patients, a few recent studies have supported its use in selected older patients with age-adapted protocols [ 24 , 59 , 82 ].…”

Section: Treatmentmentioning

confidence: 99%

“…The rate of toxic-related death was 3.8% ( n = 2). In a single-arm prospective pilot trial, 13 patients older than 65 years (range from 70 to 79 years) who had achieved CR or partial response (PR) after induction with rituximab, HD-MTX and cytarabine received a consolidation protocol of HD-ASCT based on busulfan IV at 3.2 mg/kg and thiotepa IV at 5 mg/kg [ 24 ]. The inclusion criteria included the following: Eastern Cooperative Group Performance Status (ECOG-PS) ≤ 2, Cumulative Illness Rating Scale–Geriatric score < 6 (excluding direct PCNSL symptoms), and adequate bone marrow, hepatic and renal function (creatinine clearance ≥ 60 mL/min).…”

Section: Treatmentmentioning

confidence: 99%

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Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Morales-Martínez¹,

Lozano-Sanchez²,

Durán-Peña³

et al. 2021

Cancers

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The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

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High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study

Abstract: Key Points Age-adapted high-dose chemotherapy and autologous stem cell transplantation is safe and highly effective in elderly patients with PCNSL.

Cited by 39 publications

References 25 publications

Primary central nervous system lymphoma: a narrative review of ongoing clinical trials and goals for future studies

Primary central nervous system lymphoma: a narrative review of ongoing clinical trials and goals for future studies

Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

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