Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy

Chiesa, S.; Hohaus, Stefan; Falcinelli, Lorenzo; D’Alo’, Francesco; Martelli, Massimo F.; Manfrida, S.; Bartoli, F. Beghella; Colosimo, Cesare; Valentini, Vincenzo; Aristei, Cynthia; Boccadoro, Mario

doi:10.1007/s00277-020-04220-1

Cited by 10 publications

(6 citation statements)

References 43 publications

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“…Chemoradiotherapy with TMZ prolongs the overall survival of patients with glioblastoma; accordingly, the development of severe thrombocytopenia during the course of treatment may be accompanied by treatment interruption or early termination that negatively affects survival [ 33 ]. Traditionally, the routine practice in case of developing thrombocytopenia is to discontinue the TMZ regimen and wait for the recovery of platelet count to the normal levels.…”

Section: Discussionmentioning

confidence: 99%

PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients

Amouheidari

Alirezaei

Rauh

et al. 2022

Journal of Oncology

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Background. Chemotherapy-induced cytopenia is the most frequent side effect of chemoradiotherapy in glioblastoma patients which may lead to reduced delivery of treatment. This study aims to develop a predictive model that is able to forecast the cytopenia induced by temozolomide (TMZ) during concomitant chemoradiotherapy. Methods. Medical records of 128 patients with newly diagnosed glioblastoma were evaluated to extract the baseline complete blood test before and during the six weeks of chemoradiotherapy to create a dataset for the development of ML models. Using the constructed dataset, different ML algorithms were trained and tested. Results. Our proposed algorithm achieved accuracies of 85.6%, 88.7%, and 89.3% in predicting thrombocytopenia, lymphopenia, and neutropenia, respectively. Conclusions. The algorithm designed and developed in this study, called PrACTiC, showed promising results in the accurate prediction of thrombocytopenia, neutropenia, and lymphopenia induced by TMZ in glioblastoma patients. PrACTiC can provide valuable insight for physicians and help them to make the necessary treatment modifications and prevent the toxicities.

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Section: Discussionmentioning

confidence: 99%

PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients

Amouheidari

Alirezaei

Rauh

et al. 2022

Journal of Oncology

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“…As a result, this dose was well tolerated even in elderly patients without routine administration of granulocyte colony stimulating factor. Temozolomide, as an oral alkylating agent, has shown e cacy and safety in the treatment of newly diagnosed PCNSL when combined with high dose MTX and radiotherapy [35] or as consolidation treatment when combined with etoposide [36]. As for r/r PCNSL, temozolomide combined with bruton's kinase inhibitor ibrutinib achieved an ORR of 55% and a median PFS of 5.3 months [37].…”

Section: Discussionmentioning

confidence: 99%

Specific KIR-HLA genotypes predict outcomes of refractory or recurrent primary central nervous system lymphoma

Lin

et al. 2022

Preprint

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Purpose An effective salvage regimen for re-induction of remission is lacking for refractory or recurrent primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of high dose cytarabine plus temozolomide in treating r/r PCNSL and explore the prognostic factors Methods A single-center retrospective cohort study was conducted to access the efficacy and safety of high dose cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping were performed from peripheral blood sample of each patient. Results Thirty PCNSL patients receiving AT regimen (cytarabine 3g/m2 for 2 days combined with temozolomide 150mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25–79 years). 43.4% of patients (13/30) achieved overall response with a median follow up of 16 months (95% confidence interval [CI]:11–23 months). The median PFS and OS of the cohort were 1.75 months (95% CI:1–4 months) and 19.5 months (95%CI:11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate (p = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) (p = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with the PFS (p = 0.042). But it had no impact on the OS of the cohort. Toxicity of AT treatment was mild and manageable. Conclusion AT regimen was well tolerated and patients with specific KIR-HLA genotypes may benefit from it.

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“…A recent phase 1 study of concomitant WBRT and TMZ maintenance after HD‐MTX induction has demonstrated that a 75 mg/m 2 dose of TMZ in combination with 30 Gy of WBRT did not result in dose‐limiting toxicities, with no grade 3–4 haematological toxicity. Six of nine patients treated with TMZ maintenance remain alive and without disease at 119 months of follow‐up 91 …”

Section: Treatment Of Pcnsl In the Elderlymentioning

confidence: 99%

“…Six of nine patients treated with TMZ maintenance remain alive and without disease at 119 months of follow-up. 91 Procarbazine is another alkylating agent that has been investigated for consolidation/maintenance in elderly PCNSL. Evidence for PCZ maintenance derives largely from the PRIMAIN trial, a single-arm phase 2 study featuring PCZ maintenance for patients ≥65 years after HD-MTX induction.…”

Section: Treatment Of the 'Fit' Elderly With Dose-adapted Hd-mtx-base...mentioning

confidence: 99%

Advances in treatment of elderly primary central nervous system lymphoma

et al. 2021

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The management of older individuals (≥60 years) with primary central nervous system lymphoma remains a clinical challenge. Identification of optimal therapy and delivering adequate dose intensity are two of the major issues in treating elderly patients. Premorbid performance status and comorbidities influence individualised treatment approaches and geriatric assessment tools are increasingly utilised. Optimal induction treatment remains high-dose methotrexatebased immunochemotherapy, delivery is feasible in the majority of patients and the goal of treatment remains achieving complete remission. Consolidation strategies are also relevant in the elderly, aiming to maximise duration of response and quality of life (QoL). Potential options include high-dose therapy with haematopoietic stem cell consolidation, non-myeloablative chemotherapy and whole-brain radiotherapy. Efficacy of novel agents, such as Bruton tyrosine kinase inhibitors and lenalidomide, have been reported; these represent an alternative for elderly patients unfit for chemotherapy. Prognosis remains poor, improvement of outcomes in this age group is urgently needed.

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Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy

Cited by 10 publications

References 43 publications

PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients

PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients

Specific KIR-HLA genotypes predict outcomes of refractory or recurrent primary central nervous system lymphoma

Advances in treatment of elderly primary central nervous system lymphoma

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