The outcome of peripheral T-cell lymphomas (PTCLs) is poor using standard CHOP chemotherapy. Previous studies have shown good single agent activity of gemcitabine in the relapsed/refractory setting. GDP (gemcitabine, dexamethasone and cisplatin) was developed as a secondary chemotherapy regimen in relapsed aggressive lymphomas and in a comparison to DHAP has recently been shown to have equivalent efficacy, a favourable side effect profile, and it can be delivered in the outpatient setting. At the BC Cancer Agency, GDP has recently been integrated into the primary therapy of patients with PTCLs in an attempt to improve outcomes with CHOP chemotherapy in this poor risk population.
The BC Cancer Agency Centre for Lymphoid Cancer and pharmacy databases were searched to identify all cases of newly diagnosed PTCLs with diagnoses by the WHO classification, (with the exception of ALK-positive ALCL, extranodal NK/T-cell lymphoma, cutaneous T-cell lymphoma and hepatosplenic t-cell lymphoma) that received at least one cycle of GDP chemotherapy integrated into their primary therapy, typically alternating with CHOP.
In total, 34 patients received GDP as part of their first-line treatment (PTCL-NOS n=19, ALK-neg ALCL n=10, enteropathy-type TCL n=2, angioimmunoblastic T-cell lymphoma n=3) in addition to CHOP chemotherapy. The median age was 58 years, 65% were male and the majority of patients had high risk features including stage 3 or 4 disease (94%), elevated LDH (62%). high IPI score (>3 65%; >2 82%) and 32% had bone marrow involvement. The median number of cycles of GDP was 3 (1-8). Two patients underwent consolidative treatment with high dose chemotherapy and autologous stem cell transplantation in first remission and two patients received consolidative radiotherapy. The overall response rate at the end of primary chemotherapy was 82% (CR 62%). With a median follow-up in living patients of 2.8 years the 1- and 2-year time to progression (TTP) were 50% and 36%, respectively and the corresponding estimates for OS were 78% and 64%. Interestingly, the IPI was not prognostic (2 y TTP IPI 0,1 42%, 2,3 34%%, 4,5 37.5% p=.87) even if the 2 patients undergoing transplant are excluded. GDP was generally well tolerated and only 2 patients discontinued treatment due to toxicity (renal dysfunction/hearing loss and rash) and there were no treatment-related deaths. Two patients were hospitalized for febrile neutropenia following GDP and 9 patients (26%) required GCSF support through their therapy.
The use of GDP in the primary treatment of PTCL is associated with a high response rate. Outcomes in high IPI patients compare favourably with historical results using CHOP chemotherapy and suggest that it may be able to overcome disease resistance in this poor risk group, providing rationale to explore it in further in future clinical trials of PTCLs.
Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Savage:Eli-Lilly: Consultancy.