TY - JOUR
T1 - A Phase I Study of Romidepsin in Combination With Gemcitabine, Oxaliplatin, and Dexamethasone in Patients With Relapsed or Refractory Aggressive Lymphomas Enriched for T-Cell Lymphomas
AU - Foley, Nicole
AU - Riedell, Peter A.
AU - Bartlett, Nancy L.
AU - Cashen, Amanda F.
AU - Kahl, Brad S.
AU - Fehniger, Todd A.
AU - Fischer, Anne
AU - Moreno, Chaz
AU - Liu, Jingxia
AU - Carson, Kenneth
AU - Mehta-Shah, Neha
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2024
Y1 - 2024
N2 - Introduction: Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic. Patients and Methods: We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas. A total of 24 patients were enrolled with median age 70; 6 patients had diffuse large B-cell lymphoma (DLBCL) and 18 patients had peripheral T-cell lymphomas (PTCL-NOS: 10; angioimmunoblastic T-cell lymphoma [AITL]: 7; ALK-negative anaplastic large cell lymphoma: 1). Patients had received a median of 2 prior lines of therapy and 10 patients were refractory to last line of therapy. Results: Using a standard 3 + 3 dose escalation design, the maximum tolerated dose of romidepsin was determined to be 10 mg/m2 in combination with GemOxD. There were no unexpected toxicities. The most common grade ≥ 3 treatment-emergent adverse events were thrombocytopenia (79%) and lymphopenia (46%). The overall response rate for Romi-GemOxD was 52% (12/23) with complete response (CR) rate of 43% (10/23). All 6 patients with AITL evaluable for efficacy achieved CR. Durable responses were seen in patients with AITL, PTCL-NOS and DLBCL. Without additional therapy, 4 patients remained in remission for more than 2 years, with 3 patients progressing at 46.5, 30.8, and 32.6 months and 1 remission ongoing at 83 months. A total of 4 patients proceeded to consolidative stem cell transplant following induction. Conclusion: Romi-GemOxD represents a well-tolerated, time-limited, effective option for patients, particularly for those with AITL in which durable responses were seen.
AB - Introduction: Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic. Patients and Methods: We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas. A total of 24 patients were enrolled with median age 70; 6 patients had diffuse large B-cell lymphoma (DLBCL) and 18 patients had peripheral T-cell lymphomas (PTCL-NOS: 10; angioimmunoblastic T-cell lymphoma [AITL]: 7; ALK-negative anaplastic large cell lymphoma: 1). Patients had received a median of 2 prior lines of therapy and 10 patients were refractory to last line of therapy. Results: Using a standard 3 + 3 dose escalation design, the maximum tolerated dose of romidepsin was determined to be 10 mg/m2 in combination with GemOxD. There were no unexpected toxicities. The most common grade ≥ 3 treatment-emergent adverse events were thrombocytopenia (79%) and lymphopenia (46%). The overall response rate for Romi-GemOxD was 52% (12/23) with complete response (CR) rate of 43% (10/23). All 6 patients with AITL evaluable for efficacy achieved CR. Durable responses were seen in patients with AITL, PTCL-NOS and DLBCL. Without additional therapy, 4 patients remained in remission for more than 2 years, with 3 patients progressing at 46.5, 30.8, and 32.6 months and 1 remission ongoing at 83 months. A total of 4 patients proceeded to consolidative stem cell transplant following induction. Conclusion: Romi-GemOxD represents a well-tolerated, time-limited, effective option for patients, particularly for those with AITL in which durable responses were seen.
KW - Angioimmunoblastic T-cell lymphoma
KW - Gemcitabine oxaliplatin
KW - Histone deacetylase inhibitor
KW - Peripheral T-cell lymphoma
KW - Romidepsin
UR - http://www.scopus.com/inward/record.url?scp=85213292609&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2024.11.015
DO - 10.1016/j.clml.2024.11.015
M3 - Article
C2 - 39725584
AN - SCOPUS:85213292609
SN - 2152-2650
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -