scholarly journals A SINGLE‐CENTER RETROSPECTIVE ANALYSIS OF THE TOXICITY OF HIGH‐DOSE METHOTREXATE (HDMTX) ADMINISTERED ON THE FIRST DAY OF (R)CHOP IN AGGRESSIVE NONHODGKIN LYMPHOMAS (ANHLS)

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
M Fleming ◽  
Y Huang ◽  
E Dotson ◽  
D. A Bond ◽  
J Reneau ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Single Center ◽  
Dose Methotrexate

scholarly journals Ibrutinib Monotherapy as Bridge-to-Transplant for Relapsed/Refractory Primary Oculo-Cerebral Lymphoma

2021 ◽  
Vol 10 (19) ◽  
pp. 4483
Author(s):  
Dalma Deak-Mihaly ◽  
Sabina Iluta ◽  
Sergiu Pasca ◽  
Ciprian Jitaru ◽  
Andrei Roman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Case Series ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Single Center ◽  
Malignant Lymphomas ◽  
Bridge To Transplant ◽  
Dose Methotrexate

Introduction. Primary central nervous system lymphoma is an uncommon form of extranodal non-Hodgkin’s lymphoma, with increasing incidence, a relatively aggressive course and a poor 5-year survival. Because of its localization, the therapeutic compounds used in this disease must be able to pass through the blood-brain barrier. Chemotherapy regimens based on high-dose methotrexate are currently the standard of care for all patients who can tolerate such drugs. Autologous stem cell transplantation is indicated for malignant lymphomas in the relapsed/refractory setting. Methods. Three patients, with a median age of 60 years, range 53–64, were diagnosed with primary CNS lymphoma, and treated with ibrutinib monotherapy in the Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania, between September 2018 and November 2020 All the patients were relapsed–refractory following high-dose methotrexate chemotherapy. We present our experience using ibrutinib monotherapy-based treatment as a bridge-to-transplant option on a single-center case series and a review of the literature in this field. Results. Two of the patients were given ibrutinib as a second line therapy, both achieving complete remission and being eligible for an autologous stem cell transplantation. The third patient achieved a short remission using six cycles of systemic chemotherapy, but was started on ibrutinib monotherapy, with limited results. Conclusion. Our data is limited, and these results should be confirmed by multicentric clinical trials and should be regarded as a single-center case series, with all its limitations. Still, it brings forward a new therapeutic option for this rare subtype of malignant lymphomas, which if left untreated has a dismal prognosis.

scholarly journals Impact of Anticonvulsant - Methotrexate Interactions on High Dose Methotrexate Clearance and Outcomes in Patients with Primary CNS Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4358-4358
Author(s):  
Ilana N Cypes ◽  
Angel Mier-Hicks ◽  
Jordan Scott ◽  
Adrienne Groman ◽  
Pallawi Torka ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Retrospective Analysis ◽  
Primary Cns Lymphoma ◽  
Comprehensive Cancer Center ◽  
Categorical Variables ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Specific Patient ◽  
Dose Methotrexate

Abstract Background: Patients with primary CNS Lymphoma (PCNSL) often present with neurologic complications such as focal defects, neuropsychiatric symptoms, increased intracranial pressure, aphasia, seizures, and ocular symptoms which require initiation of prophylactic or therapeutic anticonvulsants. Most anticonvulsants are notorious for their pharmacodynamic and pharmacokinetic drug interactions. The cornerstone of PCNSL therapy is the utilization of high-dose methotrexate (HD-MTX). The pharmacokinetics of HD-MTX are uniquely sensitive to both disease biology and drug interactions. Due to the importance of both HD-MTX and anticonvulsants in PCNSL patients, these medications are frequently given in concert with one another despite theoretical and proven drug interactions published in the literature. This is a retrospective analysis of patients treated with a modified R-MPV regimen (rituximab, methotrexate, procarbazine, vincristine alternating with intrathecal methotrexate) and the effects of various anticonvulsants on HD-MTX clearance. Methods: Patients ≥18 years of age with a biopsy proven diagnosis of PCNSL at Roswell Park Comprehensive Cancer Center who received R-MPV between January 2002 and December 2019 were included in this retrospective analysis. The electronic health record of each patient was reviewed for specific patient demographics, laboratory results, confounding drug interactions, toxicity, and treatment outcomes. Descriptive statistics were computed for all categorical variables. The time to MTX clearance in hours and the potential impact of concomitant use of various anticonvulsants were assessed using the Wilcoxon Rank Sum test in the case of ordinal responses and the Pearson chi-square test or Fisher's Exact test for categorical variables where appropriate. Results: A total of 67 patients met the inclusion criteria of which 53 patients (79.1%) received anticonvulsants (189 cycles of R-MPV) and 14 did not (69 cycles of R-MPV). Patients who had seizures or frontal brain PCNSL were more likely to receive anticonvulsants (p <0.001). When considering all possible medication interactions with HD-MTX, use of any interacting medication within 48 hours prior to HD-MTX was a predictor of delayed clearance (p = 0.0398). The most common confounding interaction seen in this population were with proton pump inhibitors. Levetiracetam was the most common anticonvulsant used at any point in time during treatment (83.1%). Compared to no anticonvulsant, levetiracetam did not significantly prolong HD-MTX clearance (52.6h v. 72.7h, p = 0.1586). Other anticonvulsants utilized included phenytoin (24.5%), gabapentin (3.8%), valproate (3.8%), carbamazepine (1.9%), lacosamide (1.9%), lamotrigine (1.9%), and phenobarbital (1.9%). Of the patients who received an anticonvulsant, 11 received more than one over the treatment period. Time to clearance of HD-MTX for patients not on an anticonvulsant was 53.8 hours compared to a clearance time of 68.2 hours for those who received an anticonvulsant (p = 0.0571). Patients who received anticonvulsants had a significantly higher complete response rate (79.2% vs 35.7%, p = 0.009), longer progression free survival (25.4 mo vs 3 mo, p = 0.014) and overall survival (56.6 mo vs 4.6 mo, p = 0.002) compared to those who did not (Table 1). There was no difference in grade 3/4 toxicities between anticonvulsants and no anticonvulsants except for thrombocytopenia (p = 0.047) and respiratory side effects (p = 0.035). Conclusion: Anticonvulsants are an essential component to PCNSL therapy in patients on HD-MTX. They are well tolerated, do not alter HD-MTX clearance in a clinically significant manner and may help improve patient outcomes. Figure 1 Figure 1. Disclosures Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees.

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