Romidepsin-Bendamustine Combination for Relapsed/Refractory T Cell Lymphoma

Abstract

Background: The treatment of relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL) is limited to a few agents. Romidepsin, a histone deacetylase inhibitor, was approved for PTCL treatment as a single agent in the R/R setting, yet with partial efficacy. Several attempts to combine romidepsin with other chemotherapy regimens have been reported, however, with significant toxicity. Objectives: To study the romidepsin-bendamustine combination in PTCL in an attempt to maximize efficacy while minimizing toxicity. Methods: We report on a series of 7 heavily pretreated PTCL patients (2–5 previous lines of therapy) treated with a romidepsin-bendamustine combination. Results: Four patients were not previously exposed to either drug. Of these, 2 achieved complete remission. Interestingly, 1 patient continued treatment with a prolonged progression-free survival of more than 4 years. Toxicity was minimal and no treatment-related deaths or discontinuation were noted. Significant nausea and vomiting were reported in over 50% of patients. Hematological toxicity was mild and lower than that reported for other romidepsin-chemotherapy combinations and was correlated with bone marrow involvement by lymphoma. Conclusions: Although reporting a small number of patients, our data suggest that the combination of romidepsin and bendamustine may be a feasible therapeutic option in R/R PTCL patients and merits further study.

Use of ifosfamide, carboplatin and etoposide in combination with brentuximab vedotin or romidepsin based on CD30 positivity in relapsed/refractory peripheral T‐cell lymphoma

“…Toxicity higher than grade 2 was significant for myelosuppression and infections (55%–75%) 5 . Combinations with bortezomib, bendamustine, liposomal doxorubicin, and gemcitabine have been disappointing with equivalent or lower ORRs than single agent romidepsin 6–9 . Data from phase I studies combining pralatrexate or azacytidine to romidepsin are promising with ORRs (71%–73%) and CRs (50%–55%) comparable to our results 10,11 …”

“…5 Combinations with bortezomib, bendamustine, liposomal doxorubicin, and gemcitabine have been disappointing with equivalent or lower ORRs than single agent romidepsin. [6][7][8][9] Data from phase I studies combining pralatrexate or azacytidine to romidepsin are promising with ORRs (71%-73%) and CRs (50%-55%) comparable to our results. 10,11 Brentuximab vedotin is an antibody drug conjugate consisting of an anti-CD30 monoclonal antibody and a microtubule inhibitor, monomethyl auristatin E. 3 Our study is one of the first ones to report outcomes of Bv-ICE in R/R PTCL.…”

MPT0G612, a Novel HDAC6 Inhibitor, Induces Apoptosis and Suppresses IFN-γ-Induced Programmed Death-Ligand 1 in Human Colorectal Carcinoma Cells

“…Targeting HDACs as a promising strategy to deal with anticancer treatment has been studied for decades [31,32]. Although several pan-HDAC inhibitors (e.g., vorinostat, romidepsin, and panobinostat) are currently in clinical use, those drugs were mainly approved for cutaneous T-cell lymphoma (CTCL) or multiple myeloma therapy instead of solid tumors [33,34,35]. Also, previous reports have shown numerous cytotoxicity due to the lack of selectivity of pan-HDAC inhibitors [36,37].…”

Recent developments of HDAC inhibitors: Emerging indications and novel molecules

“…It is noteworthy that romidepsin has been involved in a large number of investigational studies as part of combinatory regimens for treatment of PTCL. In the past 10 years, romidepsin has been evaluated in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (the CHOP regimen), 111 gemcitabine, 112 pralatrexate, 113 ifosfamide, carboplatin and etoposide, 114 bendamustine, 115 gemcitabine, dexamethasone and cisplatin, 116 5-azacytidine 117 and liposomal doxorubin. 104 Table 4 summarizes the clinical evidence to date.…”