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Australian Prescriber Apr 2019
Review
PubMed: 31048945
DOI: 10.18773/austprescr.2019.020 -
Targeted Oncology Apr 2019Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue...
BACKGROUND
Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL.
OBJECTIVE
As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL.
PATIENTS AND METHODS
In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1-14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m/week for 6 weeks in 7-week cycles (with vitamin B/folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%).
RESULTS
The study's primary objective was met: ORR (95% CI) was 52% (40-64%) (p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3-14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1-8.1) months and 18.0 (10.4-NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%]).
CONCLUSIONS
These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03349333.
Topics: Adult; Aged; Aminopterin; Drug Resistance, Neoplasm; Female; Folic Acid Antagonists; Follow-Up Studies; Humans; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Salvage Therapy; Survival Rate; Young Adult
PubMed: 30904980
DOI: 10.1007/s11523-019-00630-y -
Journal of Clinical Oncology : Official... Mar 2019The aim of this open-label, first-in-setting, randomized phase III trial was to evaluate the efficacy of alisertib, an investigational Aurora A kinase inhibitor, in... (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
The aim of this open-label, first-in-setting, randomized phase III trial was to evaluate the efficacy of alisertib, an investigational Aurora A kinase inhibitor, in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL).
PATIENTS AND METHODS
Adult patients with relapsed/refractory PTCL-one or more prior therapy-were randomly assigned 1:1 to receive oral alisertib 50 mg two times per day (days 1 to 7; 21-day cycle) or investigator-selected single-agent comparator, including intravenous pralatrexate 30 mg/m (once per week for 6 weeks; 7-week cycle), or intravenous gemcitabine 1,000 mg/m or intravenous romidepsin 14 mg/m (days 1, 8, and 15; 28-day cycle). Tumor tissue (disease subtype) and imaging were assessed by independent central review. Primary outcomes were overall response rate and progression-free survival (PFS). Two interim analyses and one final analysis were planned.
RESULTS
Between May 2012 and October 2014, 271 patients were randomly assigned (alisertib, n = 138; comparator, n = 133). Enrollment was stopped early on the recommendation of the independent data monitoring committee as a result of the low probability of alisertib achieving PFS superiority with full enrollment. Centrally assessed overall response rate was 33% for alisertib and 45% for the comparator arm (odds ratio, 0.60; 95% CI, 0.33 to 1.08). Median PFS was 115 days for alisertib and 104 days for the comparator arm (hazard ratio, 0.87; 95% CI, 0.637 to 1.178). The most common adverse events were anemia (53% of alisertib-treated patients v 34% of comparator-treated patients) and neutropenia (47% v 31%, respectively). A lower percentage of patients who received alisertib (9%) compared with the comparator (14%) experienced events that led to study drug discontinuation. Of 26 on-study deaths, five were considered treatment related (alisertib, n = 3 of 11; comparator, n = 2 of 15). Two-year overall survival was 35% for each arm.
CONCLUSION
In patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Aurora Kinase A; Azepines; Disease Progression; Disease-Free Survival; Drug Resistance, Neoplasm; Early Termination of Clinical Trials; Female; Humans; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Protein Kinase Inhibitors; Pyrimidines; Recurrence; Time Factors; Young Adult
PubMed: 30707661
DOI: 10.1200/JCO.18.00899 -
Advances in Radiation Oncology 2019
PubMed: 30706007
DOI: 10.1016/j.adro.2018.10.001 -
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 -
Haematologica May 2019Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor... (Comparative Study)
Comparative Study Randomized Controlled Trial
Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma (ATL). This phase II study evaluated efficacy and safety of mogamulizumab in ATL patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the US, Europe, and Latin America. With stratification by subtype, patients were randomized 2:1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n=47) or investigator's choice of chemotherapy (n=24). The primary end point was confirmed overall response rate (cORR) confirmed on a subsequent assessment at 8 weeks by blinded independent review. ORR was 11% (95%CI: 4-23%) and 0% (95%CI: 0-14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95%CI: 0.41-1.21) and, after adjustment for performance status imbalance, 0.57 (95%CI: 0.337-0.983). The most frequent treatment-related adverse (grade ≥3) events with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory ATL is an aggressive, poor prognosis disease with a high unmet need. Investigator's choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% cORR, with a tolerable safety profile.
Topics: Adult; Aged; Aged, 80 and over; Aminopterin; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Deoxycytidine; Dexamethasone; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; International Agencies; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Neoplasm Recurrence, Local; Oxaliplatin; Prognosis; Retrospective Studies; Salvage Therapy; Survival Rate; Young Adult; Gemcitabine
PubMed: 30573506
DOI: 10.3324/haematol.2018.205096 -
OncoTargets and Therapy 2018T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma... (Review)
Review
T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL) generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor), brentuximab vedotin (antibody-drug conjugate targeting CD30), chidamide (histone deacetylase inhibitor), and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody), have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients), which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL. However, it is necessary to appropriately manage opportunistic infections and secondary lymphomas possibly associated with long-lasting lymphocytopenia caused by forodesine. In this manuscript, we have summarized the currently available evidence for forodesine and discussed the clinical implications for PTCL treatment.
PubMed: 29719411
DOI: 10.2147/OTT.S140756 -
Blood Jan 2018
Topics: Aminopterin; Depsipeptides; Humans; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
PubMed: 29371206
DOI: 10.1182/blood-2017-11-817734 -
Journal of Family Medicine and Primary... 2017The peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) belongs to a heterogeneous class of aggressive neoplasms. Although several morphologic subtypes of...
The peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) belongs to a heterogeneous class of aggressive neoplasms. Although several morphologic subtypes of this tumor have been described, no particular genetic, immunological, or distinct clinical features define this disease. Patients can experience night sweats, fever, lymphadenopathy, weight loss, splenomegaly, and/or skin changes. Common laboratory tests reveal that patients have anemia, thrombocytosis, lymphocytosis, eosinophilia, hypergammaglobulinemia, or increased lactate dehydrogenase. In this case study, a patient presented with massive lymphadenopathy and right lower limb swelling, which he developed over 6 weeks. A tissue biopsy and supporting investigations confirmed the diagnosis of PTCL, NOS.
PubMed: 29302559
DOI: 10.4103/jfmpc.jfmpc_323_16 -
Case Reports in Oncology 2017Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a rare, aggressive non-Hodgkin lymphoma for which no clear standard of care has been established,...
Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a rare, aggressive non-Hodgkin lymphoma for which no clear standard of care has been established, particularly in the relapsed/refractory disease setting. Because of its rarity, randomized trials are not conducted specifically on ENKL, nasal type; however, case reports and small case series can provide important insights into potential new treatments. We present a case report of a patient with ENKL, nasal type (previously misdiagnosed as relapsing chronic sinusitis), whose disease progressed during multi-agent chemotherapy but responded to second-line treatment with single-agent pralatrexate. We discuss treatment options for relapsed/refractory ENKL, nasal type, and suggest that pralatrexate be further evaluated in this clinical setting.
PubMed: 29279697
DOI: 10.1159/000481567