Patterns of Treatment for Newly Diagnosed and Relapsed/Refractory Peripheral T-Cell Lymphoma in the Community Setting

Background: Peripheral T-Cell lymphomas (PTCL) are an uncommon, heterogeneous group of disorders that are difficult to treat due a lack of a consensus standard of care algorithms. Conventional B-cell lymphoma chemotherapy regimens have been adapted for use in PTCL but have shown low response rates, short durations of response and generally poor outcomes. Mature T/NK cell lymphoma-specific therapies are now available, however their sequencing into treatment algorithms is not defined. The objective of this study was to determine which regimens are currently being used and the associated outcomes for PTCL patients (pts) in community settings.

Patients & methods: A retrospective review was performed of newly diagnosed and relapsed/refractory pts with PTCL, including anaplastic large cell lymphoma (ALCL), PTCL not otherwise specified (NOS), and angioimmunoblastic T-cell lymphoma (AITL) treated by Regional Cancer Care Associates between January 1, 2010 and April 30, 2015. Pts were identified using the COTA software platform, which extracts data from electronic health records and permits real-time observational database analysis.

Results: 93 pts with ALCL (n=30), PTCL-NOS (n=44), or AITL (n=19) treated by 30 physicians throughout New Jersey were identified. Median age at diagnosis was 61 (range: 19-91), with ALCL pts younger than other subtypes (53 years, 65 years, 62 years, respectively). Pts were predominantly male (63%). 55 pts (81% of assessed pts) had an Ann Arbor stage of III/IV and 34 pts (41% of assessed pts) had an international prognostic index (IPI) score >3. ALK positivity was identified in 40% of assessed ALCL pts. Median time to the 1^st oncology visit from pathologic diagnosis was 29 days; time to treatment initiation was 15 days later. The analysis demonstrated significant variation in the treatment of newly diagnosed pts. As initial 1^st line therapy, there were 13 different regimens used among 21 pts with ALCL, 18 different regimens among 29 pts with PTCL-NOS, and 7 regimens used in the 16 pts with AITL. CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) was the most frequently prescribed 1^st line chemotherapy regimen, used by 37 pts (56%) and an additional 12 pts (18%) were prescribed a CHOP-like regimen. The complete response rates and duration of response for first line CHOP plus CHOP-like regimens (excluding pts consolidated by transplant n=38) was 39% / 33.7 months for all PTCL subtypes (75% CR/37.8 months for ALCL, 24% CR/26.5 months for PTCL-NOS, and 22%CR/36.9 months for AITL). The 4-year PFS and OS for these 1^st line CHOP/CHOP-like pts was 50% and 50% respectively. Transplants were performed as part of initial therapy in 12 pts (2 allo; 10 auto) with a 4-year PFS 57% and 4-year OS 55% (p=0.29 and p=0.63; log-rank, compared to CHOP without BMT). Relapsed/refractory PTCL show similar variability in treatment regimens. There were 7 different salvage regimens for the 7 ALCL pts, 15 different regimens for the 15 PTCL-NOS pts, and 5 different regimens for the 5 AITL pts. Across all patient types there were 29 unique regimens used to treat relapsed/refractory PTCL pts. Romidepsin monotherapy (n=6) and brentuximab monotherapy (n=6) were the most common regimens. Salvage transplants were performed in 6 pts (3 allo & 3 auto). From date of diagnosis ALCL (ALK positive) pts had a 4-year PFS 68% and an OS at 4-years 100%. ALCL (ALK negative) pts had a 4-year PFS of 73% and an OS 80%. PTCL-NOS pts had a 4-year PFS of 32% and OS 42% (median PFS 13 months and a median OS 30 months). AITL pts had a 4-year PFS 48% and OS 42% (median PFS 12 months and a median OS 25 months).

Conclusion: This retrospective review demonstrated significant variability in the regimens used to treat PTCL pts outside of protocol settings. Although CHOP / CHOP-like therapy was the most common initial therapy (used in 74% of pts) with transplant up-front consolidation in 12 pts (26%), there appears to be no consensus on the optimal management approach for the PTCL subtypes and in each line of therapy. No benefit was noted in our series for upfront transplant. The survival outcomes in this community based cohort are comparable with recent multi-center institutional studies (COMPLETE and Abramson et al) and demonstrate improving survival for AITL pts versus historical control. There is a need to assess the comparative effectiveness of available treatment options in these diseases to better inform future treatment decisions.