Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma

Rhun, Émilie Le; Devos, Patrick; Houillier, Caroline; Cartalat, Stéphanie; Chinot, Olivier; Stefano, Anna Luisa Di; Lepage, C.; Reyns, Nicolas; Dubois, François; Weller, Michael

doi:10.1212/wnl.0000000000008440

Cited by 23 publications

(19 citation statements)

References 10 publications

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“…There is little doubt that exposure to lomustine could be improved in patients with lomustine-sensitive tumors like oligodendrogliomas or MGMT promoter-methylated glioblastoma if the key toxicities where mitigated. One such avenue would be the administration of drugs like romiplostim, a thrombopoietin receptor agonist recently shown to allow adequate exposure to temozolomide in patients with newly diagnosed glioblastoma experiencing severe thrombocytopenia [32]. For clinical trials in recurrent glioblastoma, while lomustine remains the standard of care, differential sample size calculations and outcome expectations based on the rate of patients with MGMT promoter-methylated tumors enrolled into the trial should be considered.…”

Section: Discussionmentioning

confidence: 99%

How did lomustine become standard of care in recurrent glioblastoma?

Weller

Rhun

2020

Cancer Treatment Reviews

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Glioblastomas are the most common malignant primary intrinsic brain tumors. Their incidence increases with age, and males are more often affected. First-line management includes maximum safe surgical resection followed by involved-field radiotherapy plus concomitant and six cycles of maintenance temozolomide chemotherapy. Standards of care at recurrence are much less well defined. Minorities of patients are offered second surgery or re-irradiation, but data on a positive impact on survival from randomized trials are lacking. The majority of patients who are eligible for salvage therapy receive systemic treatment, mostly with nitrosoureabased regimens or, depending on availability, bevacizumab alone or in various combinations. In clinical trials, lomustine alone has been increasingly used as a control arm, assigning this drug a standard-of-care position in the setting of recurrent glioblastoma. Here we review the activity of lomustine in the treatment of diffuse gliomas of adulthood in various settings. The most compelling data for lomustine stem from three randomized trials when lomustine was combined with procarbazine and vincristine as the PCV regimen in the newly diagnosed setting together with radiotherapy; improved survival with PCV was restricted to patients with isocitrate dehydrogenase-mutant tumors. No other agent with the possible exception of regorafenib has shown superior activity to lomustine in recurrent glioblastoma, but activity is largely restricted to patients with tumors with O 6methylguanine DNA methyltransferase (MGMT) promoter methylation. Hematological toxicity, notably thrombocytopenia often limits adequate exposure.

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Section: Discussionmentioning

confidence: 99%

How did lomustine become standard of care in recurrent glioblastoma?

Weller

Rhun

2020

Cancer Treatment Reviews

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159

120

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“…However, temozolomide dose modifications must be weighed against the risk of jeopardizing its benefit and large-scale studies would be necessary to establish such a regimen. For dose-relevant thrombocytopenia, the thrombopoietin receptor agonist romiplostim has shown promise in a phase II trial in patients with newly diagnosed glioblastoma 26 although an effect on OS has not yet been shown. This will be the goal of the upcoming multicenter RIGOLETTO trial (EORTC-1926-BTG).…”

Section: Discussionmentioning

confidence: 99%

Sex-Dependent Analysis of Temozolomide-Induced Myelosuppression and Effects on Survival in a Large Real-life Cohort of Patients With Glioma

et al. 2022

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Objective:To investigate the association of radiochemotherapy-induced cytopenia with sex of glioma patients and its potential impact on survival.Methods:We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy (RCT) in 492 glioma patients. Histological grading, molecular pathology, surgical procedures, adjuvant chemotherapy subsequent to the RCT phase and overall survival (OS) were recorded. The extent of cytopenia was correlated with sex and outcome.Results:Treatment-induced severe cytopenia (leuko-, lympho-, neutro- and thrombocytopenia) was more frequent in women than men (44 vs. 18%, p-value 0.0002). In women with IDH-wildtype high-grade astrocytomas there was a negative correlation of severe cytopenia in general and thrombocytopenia in specific during temozolomide RCT with OS independent from other predictors (92 (77-111) vs. 73 (21-127) weeks, p-values <0.05). In men there was also a trend for this unfavorable effect. Additionally, severe cytopenia in all blood cell lineages correlated with reduced temozolomide dose exposure during RCT (all p-values <0.05 in the total cohort) and reduced dose exposure was independently associated with worse OS (hazard ratios for OS complete vs. reduced temozolomide dose in the total/female cohort: 0.66 (0.47-0.92) and 0.4 (0.24-0.69), p-values <0.05).Conclusions:Our analysis of treatment-induced cytopenia in a large cohort of glioma patients (i) confirms that women are at higher risk and (ii) demonstrates an association of cytopenia in women with shortened survival.Classification of Evidence:This study provides class II evidence that women with glioma treated with temozolomide-based concomitant radiochemotherapy have more frequent treatment-induced severe cytopenia than men and that severe myelosuppression correlates with worse OS in women.

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“…The PLATUM trial enrolled 20 patients with grade 3 or 4 thrombocytopenia during initial chemoradiation and gave weekly subcutaneous injections of the thrombopoietin receptor agonist romiplostim. With this intervention, 60% of patients were able to complete 6 cycles of TMZ [18]. Another group presented a case of using Carica papaya leaf extract for thrombocytopenia, with report improvement in platelet counts from less than 10,000/ µL to 113,000/ µL [19].…”

Section: Discussionmentioning

confidence: 99%

The use of temozolomide in a patient with chronic thrombocytopenia: A case report

Marar¹,

Houlihan²,

Shonka³

2022

J Clin Images Med Case Rep

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Thrombocytopenia is commonly experienced with Temozolomide (TMZ) during treatment for Glioblastoma (GBM). With the increasing prevalence of obesity and associated Non-Alcoholic Steatohepatitis (NASH) worldwide, chronic thrombocytopenia is becoming increasingly common, and necessitates modifications in the standard of care treatment regimen for GBM. To date, no guidelines are present addressing this dilemma. We present a case of a patient with newly diagnosed GBM and NASH-associated cirrhosis with chronic thrombocytopenia and baseline platelet count of approximately 70,000/ μL. She received brain radiation alone followed by 6 cycles of adjuvant TMZ, initially with a 50% dose reduction and subsequent dose increase based on tolerability and stability of platelet counts. This case demonstrates the relative safety of TMZ in a patient whose platelets are affected by liver disease as opposed to bone marrow insufficiency.

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Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma

Cited by 23 publications

References 10 publications

How did lomustine become standard of care in recurrent glioblastoma?

How did lomustine become standard of care in recurrent glioblastoma?

Sex-Dependent Analysis of Temozolomide-Induced Myelosuppression and Effects on Survival in a Large Real-life Cohort of Patients With Glioma

The use of temozolomide in a patient with chronic thrombocytopenia: A case report

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