Treatment with temozolomide and ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL)

Renaud, Loïc; Bossard, Jean‐Baptiste; Carpentier, Benjamin; Terriou, Louis; Cambier, Nathalie; Chanteau, Guillaume; Escure, Guillaume; Tilmont, Rémi; Barbieux, Sarah; Wémeau, Mathieu; Hieulle, Julia; Boyle, Eileen M.; Morschhauser, Franck

doi:10.1111/ejh.13667

Cited by 24 publications

(24 citation statements)

References 8 publications

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“…Most of the previously conducted clinical studies related to R/R PCNSL have studied either recurrent PCNSL or refractory PCNSL ( 14 ), or have discussed both patients as a whole ( 15 , 16 ). However, our results revealed the heterogeneity between the two groups of patients.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy or chemotherapy: a real-world study of the first-time relapsed and refractory primary central nervous system lymphoma

et al. 2023

Front. Oncol.

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BackgroundPrimary central nervous system lymphoma (PCNSL) is an uncommon variant of non-Hodgkin lymphoma (NHL) with high aggressiveness and poor prognosis. Although complete remission (CR) could be achieved with therapy, some patients remain refractory or recurrently with a worse response to salvage treatment and poor prognosis. No consensus on rescue therapy has been established currently. This study is aimed to evaluate the efficacy of radiotherapy or chemotherapy in first-time relapsed or refractory progressed PCNSL (R/R PCNSL) and analysis the prognostic factors, to explore differences between relapsed and refractory PCNSL.MethodsTotally 105 R/R PCNSL patients from Huashan Hospital between 1 January 2016 and 31 December 2020 were enrolled, underwent salvage radiotherapy or chemotherapy and received response assessments after each course. PFS1 was defined as the time from diagnosis to the first time of recurrence or refractory progression. Statistical analysis was performed with SPSS version 26.0.ResultsResponse and survival were analyzed over a 17.5months (median) follow-up. Compared to relapsed PCNSL (n = 42), refractory PCNSL (n = 63) had a shorter median PFS1 related to deep lesions. 82.4% of cases were discovered as the second relapse or progression. ORR and PFS were both higher in relapsed PCNSL than those in refractory PCNSL. ORR of radiotherapy in both relapsed and refractory PCNSL was higher than that of chemotherapy. Elevated CSF protein and ocular involvement were related to PFS and OS after recurrence respectively in relapsed PCNSL. Age ≥ 60y was unfavorable to OS-R (OS after recurrence or progression) in refractory PCNSL.ConclusionsOur results indicate that relapsed PCNSL responds well to inducing and salvage therapy and has a better prognosis compared to refractory PCNSL. Radiotherapy is effective for PCNSL after the first relapse or progression. Age, CSF protein level, and ocular involvement could be potential factors to predict prognosis.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy or chemotherapy: a real-world study of the first-time relapsed and refractory primary central nervous system lymphoma

et al. 2023

Front. Oncol.

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“…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]. Cytarabine plus temozolomide regimen produced an ORR of 43.3% in our study, which was similar to single administered cytarabine as previously reported, and the median PFS was not satisfactory.…”

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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“…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 [38] or as consolidation treatment when combined with etoposide [39]. 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 [40]. The cytarabine plus temozolomide regimen produced an ORR of 43.3% in our study, which was similar to that produced by 4 doses of cytarabine as previously reported, but the median PFS was not satisfactory.…”

Section: Discussionmentioning

confidence: 99%

Specific KIR-HLA genotypes predict the 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 the reinduction 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 to explore the associated prognostic factors. Methods A single-center retrospective cohort study was conducted to assess the efficacy and safety of high-dose cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples from each patient. Results Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m2 for 2 days combined with temozolomide 150 mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25–79 years). A total of 43.4% of patients (13/30) achieved an overall response within 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 PFS (p = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable. Conclusion The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen. Trial registration number: ChiCTR2100054482 Date of registration: 2021-12-18 Registration status: prospective registration

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Treatment with temozolomide and ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL)

Cited by 24 publications

References 8 publications

Radiotherapy or chemotherapy: a real-world study of the first-time relapsed and refractory primary central nervous system lymphoma

Radiotherapy or chemotherapy: a real-world study of the first-time relapsed and refractory primary central nervous system lymphoma

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

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

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