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Medicine Jul 2019Relapsed or refractory peripheral T-cell lymphomas are aggressive diseases. Pralatrexate is an antimetabolite. Hereby, we are reporting a pralatrexate induced durable...
Pralatrexate induced durable response in a relapsed/refractory peripheral T-cell lymphoma patient with a history of autologous stem cell transplantation: Case report of a patient followed-up over 3 years under pralatrexate treatment.
RATIONALE
Relapsed or refractory peripheral T-cell lymphomas are aggressive diseases. Pralatrexate is an antimetabolite. Hereby, we are reporting a pralatrexate induced durable response in a relapsed/refractory peripheral T-Cell lymphoma patient with a history of autologous stem cell transplantation.
PATIENT CONCERNS
A male patient born in February 1947 was diagnosed with lymphoma based on his cervical lymph node excisional biopsy.
DIAGNOSES
He was diagnosed with PTCL-NOS on February 19, 2013.
INTERVENTIONS
The patient received 6 cycles of CHOP (Cyclophosphamide, doxorubicine, vincristine, methylprednisolone) chemotherapy, which achieved a complete remission. The patient underwent autologous stem cell transplantation in December 2013. After relapse was detected in the third month of the transplantation, the patient was treated with 2 cycles of ViGePP (vinorelbine, gemcitabine, procarbazine, prednisone/ methylprednisolone) chemotherapy. The patient was considered refractory to treatment after the ViGePP chemotherapy, and he was given brentuximab vedotin. Once a full response to treatment was achieved after 2 cycles, the patient received 6 cycles of brentuximab vedotin treatment. After 6 cycles, a skin biopsy was performed and the patient was diagnosed with relapsed/refractory PTCL-NOS. Pralatrexate therapy was then started on February 1, 2016 at a dose of 30 mg/m once weekly for 6 weeks in 7-week cycles.
OUTCOMES
The patient responded to pralatrexate treatment. And he has been under pralatrexate treatment over 3 years.
LESSONS
Pralatrexate should also be kept in mind as a treatment alternative in relapsed or refractory peripheral T-cell lymphoma patients.
Topics: Aged; Aminopterin; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Peripheral; Male; Recurrence
PubMed: 31348254
DOI: 10.1097/MD.0000000000016482 -
Oncology Letters Jan 2019The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A...
The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A retrospective analysis of medical records of 82 bladder cancer patients admitted to Shengjing Hospital of China Medical University from February 2015 to February 2018 was performed. Patients treated with PTX combined with PAL served as study group (42 cases) and patients with conventional GC (gemcitabine plus cisplatin) chemotherapy regimen were the control group (40 cases). Changes in liver function indexes before and after treatment were observed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil). RT-qPCR was used for detection of relative expression levels of serum dihydrofolate reductase (DHFR) and vascular endothelial growth factor (VEGF) before and after treatment in the two groups. The clinical efficacy after treatment and adverse reactions during treatment were observed in the two groups. There was no significant difference in the clinical remission rate (RR) nor in the serum ALT, AST, ALP and TBil levels between the study and the control groups (P>0.05). Concentrations of serum ALT, AST, ALP and TBil were significantly higher than those before treatment in both groups (P<0.05). Serum ALT, AST, ALP and TBil concentrations in study group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of thrombocytopenia and leukopenia between the two groups (P>0.05). There was no significant difference in relative expression levels of serum DHFR mRNA and VEGF mRNA before treatment between the study and control groups (P>0.05). Those after treatment were significantly lower than those before treatment in both groups (P<0.05), and those after treatment in study group were significantly lower than those in control group (P<0.05). PTX combined with PAL can reduce adverse reactions of nausea and vomiting and liver function impairment during treatment and suppress tumor neovascularization. This is achieved possibly by inhibiting expression levels of DHFR and VEGF, thereby killing cancer cells. PTX combined with PAL may become a new method for the treatment of bladder cancer patients. DHFR and VEGF are expected to become novel therapeutic targets for the treatment of bladder cancer.
PubMed: 30655756
DOI: 10.3892/ol.2018.9617 -
Annals of Hematology Apr 2017
Topics: Aged; Aminopterin; Antineoplastic Agents; Dendritic Cells; Humans; Male; Myeloproliferative Disorders; Recurrence; Skin Neoplasms; Time Factors; Treatment Outcome
PubMed: 28013360
DOI: 10.1007/s00277-016-2907-4 -
Skin Therapy Letter Feb 2011A variety of novel therapeutic modalities have recently become available for patients with cutaneous T cell lymphoma (CTCL). In particular, with recent FDA approvals of... (Review)
Review
A variety of novel therapeutic modalities have recently become available for patients with cutaneous T cell lymphoma (CTCL). In particular, with recent FDA approvals of the three new agents vorinostat (Zolinza), romidepsin (Istodax), and pralatrexate (Folotyn) CTCL treatment has been transformed. Here, we offer a brief overview of these agents and discuss their place in the spectrum of current therapies for CTCL.
Topics: Antibodies, Monoclonal; Histone Deacetylase Inhibitors; Humans; Lymphoma, T-Cell, Cutaneous; Photochemotherapy; Skin Neoplasms; Stem Cell Transplantation
PubMed: 21591544
DOI: No ID Found -
Spectrochimica Acta. Part A, Molecular... May 2021In this study, a series of green, interference-free fluorimetric detection methods of the excitation-emission matrix coupled with the second-order calibration methods...
Three efficient chemometrics assisted fluorimetric detection methods for interference-free, rapid, and simultaneous determination of ibrutinib and pralatrexate in various complicated biological fluids.
In this study, a series of green, interference-free fluorimetric detection methods of the excitation-emission matrix coupled with the second-order calibration methods were proposed for the determination of ibrutinib and pralatrexate in various complicated biological fluids. The second-order advantage of the proposed method can overcome the problem of poor selectivity caused by the wide spectra of the fluorescence method. Even in the presence of uncalibrated interferences and severe peak overlap, the signal of pure substance and accurate quantitative results were still obtained. The average recoveries of the three methods were 94.5-104.9% for Alternating Trilinear Decomposition (ATLD) algorithm, 95.5-105.8% for Alternating Normalization Weighted Error (ANWE) algorithm and 94.4-105.7% for Parallel Factor Analysis (PARAFAC) algorithm, respectively. For ATLD, ANWE and PARAFAC, the relative standard deviations (RSD) were lower than 9.2%, 6.8% and 9.2%, and the RMSEPs were less than 8.1, 8.4 and 8.6 ng mL, respectively. In addition, the elliptic joint confidence region (EJCR) was adopted to further prove the accuracy of the three methods. The results showed that the three methods can accurately be quantified without significant difference. Good figures of merit parameters were also obtained. Among them, the limit of detection (LOD) and limit of quantification (LOQ) of ibrutinib and pralatrexate were in the range of 0.11-0.76 ng mL and 0.21-1.12 ng mL, respectively, which were lower than the corresponding blood concentrations. These results indicate that the proposed method provides a promising, alternative and universal analysis strategy for clinical drug monitoring.
Topics: Adenine; Algorithms; Aminopterin; Calibration; Fluorometry; Limit of Detection; Piperidines; Spectrometry, Fluorescence
PubMed: 33524816
DOI: 10.1016/j.saa.2020.119419 -
Expert Opinion on Biological Therapy Mar 2019Peripheral T-cell lymphoma (PTCL) is a relatively rare, heterogeneous group of mature T-cell neoplasms generally associated with poor prognosis, partly because of... (Review)
Review
INTRODUCTION
Peripheral T-cell lymphoma (PTCL) is a relatively rare, heterogeneous group of mature T-cell neoplasms generally associated with poor prognosis, partly because of refractoriness against conventional cytotoxic chemotherapies. To improve the outcome of patients with PTCL, the clinical development of several novel agents is currently under investigation.
AREAS COVERED
Since the first approval of pralatrexate (dihydrofolate reductase inhibitor) by the US Food and Drug Administration, belinostat, romidepsin (histone deacetylase inhibitors), and brentuximab vedotin (anti-CD30 antibody-drug conjugate) have been approved in the US, and many other countries. In addition, mogamulizumab (anti-CC chemokine receptor 4 antibody), chidamide (histone deacetylase inhibitor), and forodesine (purine nucleoside phosphorylase inhibitor) have been approved in Asian countries, including China, and Japan. In this review, we have summarized the available data regarding these approved agents and new agents currently under development for PTCL.
EXPERT OPINION
Novel agents will be a promising therapeutic option in selected patients with relapsed/refractory PTCL and will change the daily clinical practice in the treatment of PTCL. However, these are not a curative option when used as a single agent. Further clinical developments are expected, comprising 1) combination therapies of new agents with cytotoxic chemotherapies; 2) 'novel-novel' combinations; 3) immune therapies, including chimeric antigen receptor T-cell therapy; and 4) predictive marker analysis.
Topics: Aminopterin; Aminopyridines; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benzamides; Brentuximab Vedotin; China; Depsipeptides; Drug Approval; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Immunoconjugates; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local; Sulfonamides
PubMed: 30658046
DOI: 10.1080/14712598.2019.1572746 -
Journal of Pharmaceutical and... Nov 2016Pralatrexate (PTXT) is an antineoplastic folate analog and the chemical name is (2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl] benzoyl] amino]...
Pralatrexate (PTXT) is an antineoplastic folate analog and the chemical name is (2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl] benzoyl] amino] pentanedioic acid. Degradation products of PTXT drug product (DP) under different forced degradation conditions have been studied using LC-PDA and LC-MS techniques. PTXT DP was subjected to forced degradation under the conditions of hydrolysis, photolysis, oxidation, and heat in accordance with ICH guidelines. The LC-MS compatible HPLC method was developed and stressed solutions were chromatographed on reversed phase HPLC. The degradation products were monitored at a wavelength of 242nm. Stress study revealed that PTXT was sensitive towards acid, alkali, peroxide, light and heat. The degradation impurities (I-IX) were identified and characterized using LC-PDA and mass spectral data.
Topics: Aminopterin; Chromatography, Liquid; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 27643862
DOI: 10.1016/j.jpba.2016.08.023 -
Seminars in Hematology Jan 2014The peripheral T-cell lymphomas (PTCLs) include a pathologic and clinically heterogeneous group of mature aggressive T-cell lymphomas, with overall inferior prognoses... (Review)
Review
The peripheral T-cell lymphomas (PTCLs) include a pathologic and clinically heterogeneous group of mature aggressive T-cell lymphomas, with overall inferior prognoses compared with aggressive B-cell lymphomas. Diagnosis by expert pathologic analysis is paramount in differentiating the multiple different clinicopathologic subtypes. The clinical presentations of PTCLs are variable, from that of an indolent nature to an aggressive behavior, although most have natural histories as aggressive lymphomas. First-line treatment for most PTCLs should include multi-agent chemotherapy with consideration of inclusion of etoposide chemotherapy for younger patients, as well as consolidation with autologous stem cell transplantation (SCT) in select cases. For patients with disease relapse, salvage therapy followed by autologous or allogeneic SCT should be considered. Additionally, several novel therapeutic agents have been approved by the US Food and Drug Administration (FDA) for relapsed/refractory PTCL, including romidepsin, pralatrexate, and brentuximab vedotin, the latter specifically for anaplastic large cell lymphoma. Furthermore, there are a number of new, targeted agents being studied. In order to improve outcomes for PTCL, it remains critical to consider these patients for clinical studies. In this article, we examine the recent progress and changing landscape of treatment of PTCL.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Peripheral; Prognosis; Recurrence
PubMed: 24468312
DOI: 10.1053/j.seminhematol.2013.11.006 -
The Australasian Journal of Dermatology Aug 2021We report the case of a 59-year-old woman with stage IV erythrodermic mycosis fungoides (MF) and large cell transformation who, despite failing multiple previous...
Complete remission of stage IV erythrodermic mycosis fungoides with large cell transformation through combination of pralatrexate and romidepsin followed by allogeneic hematopoietic stem cell transplantation.
We report the case of a 59-year-old woman with stage IV erythrodermic mycosis fungoides (MF) and large cell transformation who, despite failing multiple previous treatments, achieved complete remission through a combination of pralatrexate and romidepsin followed by allogeneic hematopoietic stem cell transplantation (alloSCT). Further studies are needed in focussing on this combined regimen in treating cutaneous T-cell lymphoma (CTCL) and its efficacy as a bridging regimen in facilitating successful alloSCT.
Topics: Aminopterin; Antibiotics, Antineoplastic; Depsipeptides; Female; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Mycosis Fungoides; Remission Induction; Skin Neoplasms; Treatment Outcome
PubMed: 34028795
DOI: 10.1111/ajd.13606 -
Leukemia & Lymphoma Nov 2013Balancing efficacy and safety of drugs is key for successful cancer therapy, as adverse reactions can prohibit the use of efficacious treatments. Pralatrexate (PDX) is a...
Balancing efficacy and safety of drugs is key for successful cancer therapy, as adverse reactions can prohibit the use of efficacious treatments. Pralatrexate (PDX) is a novel antifolate with a higher affinity for tumor cells than methotrexate, Food and Drug Administration (FDA) approved for use in relapsed and refractory peripheral T-cell lymphoma (PTCL) and transformed mycosis fungoides (T-MF). Patients with T-MF have a higher incidence of adverse events than patients with other lymphomas, necessitating a lower recommended dose of 15 mg/m(2) (vs. 30 mg/m(2) for PTCL). Dose-limiting toxicity (DLT) mucositis occurs in about 25% of patients with T-MF, but milder mucositis is observed in almost all patients with T-MF, frequently leading to therapy discontinuation despite clinical response. Leucovorin rescue is the standard of care for high-dose methotrexate therapy, but has not been studied or recommended for use with PDX. We report our clinical experience using leucovorin with PDX (30 mg/m(2)) with good clinical response and no DLTs. Prophylactic leucovorin deserves further investigation in prospective clinical trials to allow patients with cutaneous lymphomas to receive the full benefit of PDX therapy without intolerable toxicity.
Topics: Adult; Aged; Aged, 80 and over; Aminopterin; Female; Folic Acid Antagonists; Humans; Leucovorin; Lymph Nodes; Lymphoma, T-Cell, Peripheral; Male; Mycosis Fungoides; Premedication; Skin; Tomography, X-Ray Computed
PubMed: 23442065
DOI: 10.3109/10428194.2013.779688