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Clinical Lymphoma, Myeloma & Leukemia Nov 2020We examined patient characteristics, treatments, and outcomes of patients with transformed mycosis fungoides (tMF) from COMPLETE: a large, multicenter, prospective...
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.
RESULTS
Of the 499 patients enrolled in COMPLETE, 17 had tMF. Median age was 61; 53% were male, 9 had elevated lactate dehydrogenase, and 9 had lymph node involvement. Approximately one-quarter of the patients were African American and 47% had CD30+ disease. Median time to transformation was 53 months. All patients received systemic therapy, with 19% receiving concomitant radiotherapy. Most patients (87%) received single agents, including liposomal doxorubicin, pralatrexate, and gemcitabine. Eight patients (50%) had reported responses to therapy. Median survival was 18 months. One- and 2-year survival rates were 56% and 44%, respectively.
CONCLUSIONS
tMF often expresses CD30 and presents with lymph node involvement. Responses have been seen with single agents, but survival remains poor. Novel treatment approaches are urgently needed to improve outcomes.
Topics: Aged; Cohort Studies; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Prospective Studies; Skin Neoplasms; Treatment Outcome
PubMed: 32532611
DOI: 10.1016/j.clml.2020.05.001 -
Oncotarget May 2020Multiple myeloma (MM) is the second most common hematologic malignancy. While major advances have been made in the disease, it is still incurable. Although...
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 exhibits a potency and pattern of activity distinct from its predecessors like methotrexate (MTX). We sought to understand the activity and mechanisms of resistance of multiple myeloma to these drugs, which could also offer potential strategies for selective use of the drug. We demonstrate that PDX and MTX both induce a significant decrease in cell viability in the low nanomolar range, with PDX exhibiting a more potent effect. We identified a series of myeloma cell lines exhibiting markedly different patterns of sensitivity to the drugs, with some lines frankly resistant, and others exquisitely sensitive. These differences were largely attributed to the basal RFC (Reduced Folate Carrier) mRNA expression levels. RFC mRNA expression correlated directly with rates of drug uptake, with the most sensitive lines exhibiting the most significant intracellular accumulation of pralatrexate. This mechanism explains the widely varying patterns of sensitivity and resistance to pralatrexate in multiple myeloma cell lines. These findings could have implications for this class of drugs and their role in the treatment of multiple myeloma.
PubMed: 32405334
DOI: 10.18632/oncotarget.27516 -
Gan To Kagaku Ryoho. Cancer &... Jan 2020Pralatrexate(PDX)has been approved for the treatment of relapsed/refractory peripheral T-cell lymphoma(PTCL), including angioimmunoblastic T-cell lymphoma(AITL). Oral...
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. LV administration minimizes adverse effects for patients receiving high-dose methotrexate. However, the optimal dose and schedule of LV in PDX treatment has not yet been established. In the future, clinical trials on the use of LV for PDX-induced oral mucositis are needed.
Topics: Aged; Aminopterin; Antineoplastic Combined Chemotherapy Protocols; Folic Acid Antagonists; Humans; Leucovorin; Lymphoma, T-Cell; Male; Neoplasm Recurrence, Local
PubMed: 32381871
DOI: No ID Found -
Medicine May 2020
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: Erratum.
PubMed: 32358408
DOI: 10.1097/MD.0000000000020260 -
Expert Review of Hematology Jun 2020Peripheral T cell lymphomas (PTCL) are a heterogenous group of lymphoproliferative disorders which are generally not curable with conventional chemotherapy and... (Review)
Review
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. Pharmacokinetics and mechanism of action of pralatrexate are discussed as well as its clinical efficacy and safety in comparison to other agents available in R/R PTCL.
EXPERT OPINION
Pralatrexate is an active agent in relapsed/refractory PTCL with lower response rates seen in patients with angioimmunoblastic T cell lymphomas. Mucositis is the most frequently observed adverse event and this can be mitigated by the use of leucovorin along with cyanocobalamin and folic acid.
Topics: Aminopterin; Humans; Lymphoma, T-Cell, Peripheral
PubMed: 32293930
DOI: 10.1080/17474086.2020.1756257 -
Journal of Clinical and Experimental... 2020
Relapsed refractory nodal peripheral T-cell lymphoma with follicular helper T-cell phenotype was initially resistant to pralatrexate and confirmed to be unresponsive to subsequent forodesine, but responded to re-instituted pralatrexate.
Topics: Aged; Aminopterin; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymph Nodes; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local; Prednisone; Purine Nucleosides; Pyrimidinones; T-Lymphocytes, Helper-Inducer; Vincristine
PubMed: 32224563
DOI: 10.3960/jslrt.18031 -
Journal of Medical Case Reports Mar 2020Extranodal 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...
Pralatrexate as a bridge to allogeneic hematopoietic stem cell transplantation in a patient with advanced-stage extranodal nasal-type natural killer/T cell lymphoma refractory to first-line chemotherapy: a case report.
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. However, there is controversy over which type of chemotherapy is most appropriate and effective as a bridge to autologus or allogeneic hematopoietic stem cell transplantation in patients with newly diagnosed disseminated advanced-stage or relapsed extranodal natural killer/T cell lymphoma because of cancer chemoresistance or associated complications. Pralatrexate is the first US Food and Drug Administration-approved novel agent for the treatment of refractory/recurrent peripheral T cell lymphomas. In our case, pralatrexate was used as a successful bridge to allogeneic hematopoietic stem cell transplantation in a patient with advanced-stage disseminated extranodal natural killer/T cell lymphoma refractory to first-line chemotherapy.
CASE PRESENTATION
We presented a case report of a 29-year-old Asian man diagnosed as having stage IV disseminated extranodal natural killer/T cell lymphoma, nasal type, with skin and bone marrow involvement, whose disease was primary refractory to first-line dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy, but obviously responded to treatment with two cycles of single-agent pralatrexate treatment. Monitoring Epstein-Barr virus viremia revealed dramatic downregulation. In addition to complete remission of the involvement of bone marrow and nasal cavity, skin involvement also obtained partial remission. The extranodal natural killer/T cell lymphoma successfully achieved complete remission after a bridge to allogeneic hematopoietic stem cell transplantation.
CONCLUSIONS
This is the first study to present pralatrexate as a successful bridge to allogeneic hematopoietic stem cell transplantation in a 29-year-old Asian male patient with advanced-stage extranodal natural killer/T cell lymphoma refractory to first-line dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy. This case provides a novel treatment opinion for extranodal natural killer/T cell lymphoma, especially for the Far East Asian population.
Topics: Adult; Allografts; Aminopterin; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Neoplasm Staging; Remission Induction; Taiwan; Transplantation Conditioning
PubMed: 32183896
DOI: 10.1186/s13256-020-02363-3 -
Scientific Reports Dec 2019Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent...
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. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29-80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m/wk (range, 15.0-33.0 mg/m/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6-24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7-1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4-9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.
Topics: Aged; Aged, 80 and over; Aminopterin; Antineoplastic Agents; Disease Management; Drug Resistance, Neoplasm; Female; Humans; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Neoplasm Staging; Prognosis; Recurrence; Retreatment; Retrospective Studies; Treatment Outcome
PubMed: 31889144
DOI: 10.1038/s41598-019-56891-0 -
Hematological Oncology Feb 2020The peripheral T-cell lymphomas (PTCL) are rare and heterogeneous diseases characterized by an unfavorable prognosis. Chemotherapy is standard upfront treatment in most...
The peripheral T-cell lymphomas (PTCL) are rare and heterogeneous diseases characterized by an unfavorable prognosis. Chemotherapy is standard upfront treatment in most patients, but responses are short-lived with few FDA-approved "novel" agents available. We sought to define the impact of these novel agents as single agents or in clinical trials on the outcomes of patients with PTCL. From January 1994 to May 2019, adult patients with PTCL who were managed at our institution were included in this analysis. In addition to patients with incomplete data, those diagnosed with large granular lymphocytic leukemia and cutaneous T-cell lymphoma (CTCL) except for transformed mycosis fungoides were excluded. Statistical analyses were performed using SAS version 9.4. There were 219 patients included in the analysis. The median age at diagnosis was 56 years (range, 18-90 years). First line therapies mostly consisted of combination chemotherapy (75%). There was a statistical difference among patients who received chemotherapy, novel agents alone and in chemotherapy-free combinations, other, and no treatment (P < .0001). In patients who were treated with second line chemotherapy, novel agents alone and in combination without chemotherapy, or other, there was a still a survival benefit favoring novel agents (P = .0417). In the third line, there was no statistical difference among the three groups (P = .569). All patients who received novel therapies and underwent autologous stem cell transplant (autoSCT) achieved a complete response (CR) and had a better survival compared with patients who underwent chemotherapy who had a 70% CR rate prior to autoSCT (P = .046). Exposure to FDA-approved novel agents, immunoepigenetic trials, and clinical trials in general was associated with an overall survival (OS) benefit (P = .003, P = .04, and P = .006, respectively). These data suggest that patients who receive novel agents have superior outcomes compared with patients without exposure to novel therapies who receive chemotherapy-predicated treatments.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 31872891
DOI: 10.1002/hon.2705 -
Pralatrexate Induces Long-Term Remission in Relapsed Subcutaneous Panniculitis-Like T-Cell Lymphoma.Annals of the Academy of Medicine,... Sep 2019
Topics: Adult; Aminopterin; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cisplatin; Cyclophosphamide; Deoxycytidine; Dexamethasone; Doxorubicin; Folic Acid Antagonists; Humans; Lymphohistiocytosis, Hemophagocytic; Lymphoma, T-Cell, Peripheral; Male; Neoplasm Recurrence, Local; Panniculitis; Prednisone; Remission Induction; Subcutaneous Fat, Abdominal; Vincristine; Gemcitabine
PubMed: 31737895
DOI: No ID Found