pralatrexate

Pralatrexate (Folotyn; PLX) and belinostat (Beleodaq; BLS) are registered for the treatment of patients with peripheral T-cell lymphoma (PTCL) and are being considered for other lymphomas. In this study we investigated whether BLS had the ability to potentiate the cytotoxicity of PLX. A panel of lymphoma cell lines was used for the combination studies: the B-cell SUDHL-4, SUDHL-5, HT, Jeko-1 and T-cell Karpas-299 and Hut-78. Uptake of PLX was mediated by the reduced folate carrier (RFC). PLX showed a 6-fold better RFC substrate affinity compared to methotrexate, and 2-fold better than levoleucovorin (l-LV)...

Histone deacetylase inhibitors (HDACi) are active agents for peripheral T-cell lymphoma (PTCL). Anecdotally angioimmunoblastic T-cell lymphoma (AITL) appears to respond better than PTCL-not otherwise specified (NOS) to HDACi. The new World Health Organization classification shows that a subgroup of PTCL carries similarities in phenotype and gene expression profiling to AITL, comparable to T follicular helper (TFH) cells. The disease might behave similarly to AITL when treated with HDACi. We analyzed 127 patients with AITL or PTCL-NOS treated with HDACi at relapse as a single agent or in combination...

INTRODUCTION: Pralatrexate is a folate analogue inhibitor of dihydrofolate reductase exhibiting high affinity for reduced folate carrier-1 with antineoplastic and immunosuppressive activities, similar to methotrexate. Despite advances in multi-modality treatment strategies, the survival rates for children with high-risk neuroblastoma have failed to improve. Therefore, the intense research continues in order to identify the ideal novel agent or combination of chemotherapy drugs to treat high-risk neuroblastoma...

No abstract text is available yet for this article.

While pralatrexate has been successfully developed for the treatment of T-cell lymphoma, the mechanistic basis for its T-cell selectivity and acquired resistance remains elusive. In an effort to potentially identify synergistic combinations that might circumnavigate or delay acquired pralatrexate resistance, we generated resistant cells lines over a broad concentration range. Pralatrexate-resistant cell lines H9-12 and H9-200 were developed, each exhibiting an IC50 of 35 and over 1000 nM, respectively. These lines were established in vitro from parental H9 cells...

Angioimmunoblastic T-cell lymphoma (AITL) is a histological subtype of peripheral T-cell lymphoma associated with a poor prognosis. This post-hoc pooled analysis aims to provide insight about the efficacy of pralatrexate monotherapy in a subset of twenty-nine patients with relapsed or refractory (r/r) AITL drawn from two prospective registration trials completed in China and Japan. After a median of two prior lines of therapy, an overall response rate of 52% (15/29 patients; 95% CI 0.34, 0.70) was demonstrated...

INTRODUCTION: We examined patient characteristics, treatments, and outcomes of patients with transformed mycosis fungoides (tMF) from COMPLETE: a large, multicenter, prospective cohort study of peripheral T-cell lymphoma patients in the United States. METHODS: Patients with tMF were enrolled in COMPLETE at the time of transformation. For this analysis, we identified patients with tMF with completed baseline, treatment, and follow-up records. Median survival was assessed using Kaplan-Meier methodology...

Multiple myeloma (MM) is the second most common hematologic malignancy. While major advances have been made in the disease, it is still incurable. Although antifolate-based drugs are not commonly used to treat myeloma, new generation analogs with distinct patterns of preclinical and clinical activity may offer an opportunity to identify new classes of potentially active drugs. Pralatrexate (PDX), which was approved for the treatment of relapsed or refractory peripheral T-cell lymphoma in 2009, may be one such drug...

Pralatrexate(PDX)has been approved for the treatment of relapsed/refractory peripheral T-cell lymphoma(PTCL), including angioimmunoblastic T-cell lymphoma(AITL). Oral mucositis is the most common and severe adverse effect of PDX that often leads to dose reduction or omission. Herein, we report a 65-year-old man with AITL, who received PDX treatment after a second relapse. This drug was effective; however, the adverse effects, such as oral mucositis, were severe. Therefore, leucovorin(LV)was administered to prevent the adverse effect, resulting in continuation of the PDX treatment for 8 months...

No abstract text is available yet for this article.

INTRODUCTION: Peripheral T cell lymphomas (PTCL) are a heterogenous group of lymphoproliferative disorders which are generally not curable with conventional chemotherapy and associated with inferior outcomes. Pralatrexate is a novel folate analog, the first FDA approved drug) for the treatment of relapsed/refractory (R/R) PTCL. AREAS COVERED: This paper provides a comprehensive review of PubMed literature describing the use of pralatrexate in R/R peripheral T-cell lymphoma...

No abstract text is available yet for this article.

BACKGROUND: Extranodal natural killer/T cell lymphoma, nasal type, is one of the more common subtypes of mature T cell lymphoma, especially in the Far East Asian population. This aggressive histologic subtype of peripheral T cell lymphomas is frequently susceptible to exposure of Epstein-Barr virus infection. The optimal treatment is not well elucidated. For stage IV disseminated extranodal natural killer/T cell lymphoma, induction chemotherapy with consolidative autologus or allogeneic hematopoietic stem cell transplantation is recommended as the major first-line treatment...

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea...

No abstract text is available yet for this article.

The purpose of our study was to evaluate the efficacy of a combination of pralatrexate plus oxaliplatin in advanced Esophago-Gastric cancer (EGC), analyze the impact of polymorphisms in folate metabolism pathway genes on toxicity and efficacy of pralatrexate and to evaluate microRNA profile of tumor epithelium as a predictive biomarker. This was a two-stage trial with a safety lead in cohort and a primary endpoint of overall response rate (ORR). Patients received biweekly intravenous oxaliplatin (85 mg/m2) and pralatrexate (Dose level 1 [D1], 120 mg/m2; dose level -1 [D-1] 100 mg/m2)...

Background: Although randomized studies are designed to assess overall survival (OS) benefit, the conduct of regulatory studies in patients with orphan diseases can be timely and costly without offering the same commercial return on the investment. The peripheral T-cell lymphomas (PTCL) represent a rare group of heterogeneous lymphoid malignancies with very poor prognosis. PROPEL was a pivotal phase II study that led to the accelerated approval of pralatrexate for patients with relapsed or refractory PTCL...

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...

Hepatosplenic T-cell lymphomas (TCLs) are a rare, aggressive subset of TCLs, accounting for less than 5% of all peripheral T-cell and natural killer (NK) cell lymphomas. We report the case of a CD3 negative hepatosplenic T-cell lymphoma in a 42-year-old female, who presented with left-sided abdominal pain. She underwent a liver biopsy that showed marked abnormal sinusoidal lymphoid infiltration. PET scan revealed increased splenic and pharyngeal lymph node uptake. Immunophenotype was remarkable for negative CD3, gamma delta T-cell receptor, and alpha beta-T-cell receptor expression...

No abstract text is available yet for this article.