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Specific Therapy for Lymphomas
Published in Tariq I Mughal, John M Goldman, Sabena T Mughal, Understanding Leukemias, Lymphomas, and Myelomas, 2017
Tariq I Mughal, John M Goldman, Sabena T Mughal
Over the past decade, efforts to assess novel agents for the therapy of PTCL suggest encouraging early responses with the nucleoside analogue forodesine. This is an inhibitor of the key enzyme that phosphorylates guanosine to guanine. A phase I trial is currently in progress. Pralatrexate, a novel antifolate has just entered clinical trials, following pre-clinical studies suggesting that it could be a specific agent for PTCL. A variety of other drugs, including histone deacetylases, temsirolimus, and bortezomib are now being investigated in phase I studies.
Cutaneous lymphomas
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Reinhard Dummer, Elaine S Jaffe
Currently, a number of other new substances, including forodesine (a purine nucleoside phosphorylase inhibitor) and APO 866 (a specific inhibitor of niacinamide phosphoribosyltransferase), have shown significant efficacy in animal models and early trials. CTCL are model tumors for other lympho-proliferative malignancies.
Contemporary strategies to improve outcomes for peripheral T-cell lymphoma patients following the failure of first-line therapy
Published in Expert Review of Hematology, 2020
Avyakta Kallam, James O. Armitage
A pivotal phase II study was conducted in Japan evaluating forodesine in relapsed/refractory PTCL [52]. Forodesine was administered orally, 300 mg twice daily. Among the 41 evaluable patients, the ORR was 24%, with a CR of 10%. The median PFS and OS were 1.9 and 15.6 months, respectively. The 2 year OS was 39%. Grade3/4 lymphopenia was seen in 96% of patients, which was likely the cause of the infections. Notably, five patients developed Epstein barr virus-positive DLBCL, likely secondary to immunosuppression. High rates of infections, particularly Pneumocystis jiroveci, and bacterial pneumonias were also reported. This drug was approved for use in relapsed/refractory PTCL in Japan in 2017. Given the high rates of lymphopenia, this drug is yet to be adopted in the USA. Nevertheless, the purine pathway appears to be an attractive T cell target and new drugs are being developed with a focus on this pathway.
Development of new agents for peripheral T-cell lymphoma
Published in Expert Opinion on Biological Therapy, 2019
Yuta Ito, Shinichi Makita, Kensei Tobinai
Although the late-phase clinical development of oral forodesine was halted in Western countries [44], clinical trials for T-cell lymphomas were continued in Japan [45,46]. A pivotal phase I/II study of forodesine for relapsed PTCL was conducted [47]. Forodesine was administered at a dose of 300 mg twice daily (BID). In the phase I part, no DLTs were reported. In the phase Ⅱ part, from 41 evaluable patients, the ORR was 22%, which included 4 patients with CR and 5 patients with PR. The median PFS and OS were 2.0 months and 14.5 months, respectively. The most common observed grade 3/4 adverse events were: lymphopenia (96%), leukopenia (42%), neutropenia (33%), thrombocytopenia (25%), and anemia (20%). Notably, 5 patients (3 patients with AITL and 2 patients with PTCL-NOS) developed diffuse large B-cell lymphoma (DLBCL). Four out of the 5 patients had Epstein-Barr virus (EBV)-positive DLBCL, which suggested that long-term severe lymphocytopenia might be associated with the development of these secondary lymphomas. Based on these results, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in 2017. At present, forodesine is available in clinical practice only in Japan.