Gemcitabine, Dexamethasone, and Cisplatin (GDP) As Secondary Chemotherapy In Relapsed/Refractory Peripheral T-Cell Lymphoma
Authors: Parkin Stephen , Connors Joseph M. , Sehn Laurie H. , Villa Diego , Klasa Richard , Gerrie Alina S. , Gascoyne Randy D. , Shenkier Tamara , Toze Cynthia L. , Shepherd John D. , Song Kevin , Savage Kerry J. 
Published: October 2019

Abstract

Introduction
The only known curative option for relapsed/refractory peripheral T-cell lymphoma (PTCL) is secondary chemotherapy followed by high dose chemotherapy and stem cell transplant (HDC/SCT), if chemosensitivity is demonstrated. The optimal choice of regimen in this setting, as well as in the transplant ineligible population is unknown. Gemcitabine, dexamethasone, and cisplatin (GDP) was developed as an alternative to DHAP with a favorable side effect profile and administration in the outpatient setting. Since 2002, it has been used as the preferred second-line regimen in patients (pts) with relapsed aggressive lymphoma at the BC Cancer Agency (BCCA), including those with PTCL intended for treatment with HDC/SCT, as well as for selected pts treated with palliative intent.

Patients and Methods
The BCCA Lymphoid Cancer database, provincial cancer pharmacy database, and the Leukemia/BMT Program of BC database were screened to identify all pts who received GDP for relapsed/refractory PTCL, excluding cutaneous ALCL. Clinical factors and whether transplant was planned at the time of relapse/progression were collected. Disease refractory to primary therapy was defined as progressive disease (PD) during primary treatment or relapse within 3 months (m) of treatment completion. All endpoints were calculated from the date of the first cycle of GDP unless stated otherwise.

Results
51 pts were identified between 2002 and 2012 with either relapsed (n=31, 61%) or primary refractory (n=20, 39%) PTCL with the following histologic subtypes: PTCL-NOS, n=17 (33%); ALCL, n=16 (31%) [ALK-positive, n=4 (8%); ALK-negative, ALCL n=10 (20%); ALK status unknown, n=2 (4%)]; AILT, n=13 (25%); NK/T cell nasal type, n=4 (8%); hepatosplenic, n=1 (2%); subcutaneous panniculitis-like, n=2 (4%).
First-line treatment consisted of a CHOP-like regimen in the majority of pts (n=48) and one patient with NK/TCL received SMILE. Two pts with NK/TCL received radiation alone. The median time to progression or relapse after initial diagnosis was 7.4 m (range 0.8-150.2). At relapse, the median age was 56 years (y) (range 17-86), 43% had an elevated LDH and most had advanced stage disease (stage III/IV, 88%), good performance status (PS 0-1, 69%) and a high or high-intermediate secondary IPI (sIPI >3, 57%). Pts received an average of 3 cycles of GDP (range 1-6). In total, 36 pts (71%) were planned for HDC/SCT, based on age and lack of significant comorbidities, following a response to GDP. Those planned for transplant were more likely to be younger (< 60 y) (p=.050) with a good PS (0-1) at relapse (p=0.049) but had a similar sIPI risk distribution (p=0.195). Of these, 26 ultimately underwent HDC/SCT (transplant rate 72%; auto, n=15; allo, n=11 [non-myeloablative n=2]). Pts who underwent alloSCT (vs autoSCT) were more likely to have disease that was refractory to primary therapy (p=.045). Of the 10 pts planned for SCT who did not undergo transplant, 8 were due to PD, 1 did not have a matched sibling donor, and 1 refused transplant.
The overall response rate (ORR) to GDP for all 51 pts was 80% (CR 47%) and with a median follow-up of 10.4 m for living pts, the 2 y progression free survival (PFS) following GDP was 25% and the 2 y overall survival (OS) was 43% with no differences amongst the histologic subtypes. For pts planned for transplant, the ORR was 83% (CR 58%). The 2 y PFS and OS for this group intended for transplant were 30% and 50%, respectively, and those with relapsed disease (n=22) had a superior outcome to those with primary refractory disease (n=14) (2 y PFS 42.5% vs 9%, p=.0027). The 2 y post-transplant OS was 53% and there was no difference observed between the relapsed and refractory pts who were ultimately transplanted (p=.23). For all non-transplanted pts (n=25), the median PFS after GDP was 4.4 m and the median OS was 6.8 m. In responding pts, the median duration of response was 6.8 m. The small group of non-transplanted pts with a good PS (0-1) at the time of GDP, had an improved PFS (7.9 m vs 1.6 m, p=.044) and median OS (3.7 y vs 4.2 m) following GDP with 3 pts alive and without PD. Overall, GDP was well tolerated with no treatment related deaths.

Conclusion
Our results suggest that GDP is an effective secondary therapy for relapsed PTCL and can lead to long-term survival, especially in those pts who subsequently undergo HDC/SCT. Selected pts with good PS may have durable remissions in the palliative setting.

Disclosures:
Off Label Use: Off label use of gemcitabine in the treatment of PTCLs. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Savage:Eli-Lilly: Consultancy.