Outcomes Following Salvage Therapy in Primary Refractory Peripheral T-Cell Lymphoma (PTCL)

Background: Resistance to conventional anthracycline-based regimens (CHOP/CHOEP) and the emergence of primary refractory disease remains a clinical challenge in PTCL, and is observed in ≈25% of patients. Outcomes in the setting of primary refractory disease, particularly for those patients who fail to achieve a remission with second-line chemotherapy, are poorly described and the optimal therapeutic strategy for these patients remains uncertain. Patients and Methods: We identified 159 patients with PTCL who received multi-agent, anthracycline-based treatment from 1988 to 2011 in the PTCL database at our institution. Primary refractory disease, defined as disease progression during initial therapy or relapse within 6 months of its completion, was observed in 58 (36%) of patients. Results: The median age at diagnosis with primary refractory PTCL was 49 years (range, 18.8-77.1). Median follow up was 2.7 years among surviving patients (95% CI, 1.2-6.3). Median overall survival (OS) was 1.1 years (95% CI, 0.7-1.9). The median number of lines of therapy underwent by patients was 3 (range, 1-9). PTCL, NOS (n=24), angioimmunoblastic T-cell lymphoma (n=6), and ALK-positive anaplastic large cell lymphoma (n=7) accounted for the majority (63.8%) of these patients. No difference in OS was observed between patients who failed to respond to initial therapy and those who relapsed within 6 months after a first remission (median OS 0.9 [95% CI, 0.6-1.9] vs. 1.3 [95% CI, 0.5-6.3], p=0.6). After developing primary refractory disease, 48.3% of patients received aggressive, multi-agent salvage regimens (ICE, n=16; DHAP, n=3; ESHAP, n=6; other, n=3), 29.3% of patients received other systemic therapies (HDAC inhibitor, n=1; gemcitabine-based therapies, n=5; pralatrexate, n=3; other, n=8), and 22.4% of patients received no systemic therapies. Patients who received no systemic salvage therapy had reduced OS compared to both patients who received aggressive regimens and patients who received other types of systemic therapies (median OS 0.3 [95% CI, 0.2-1.1] vs. 1.7 [95% CI, 0.8-11.7] vs. 1.3 [95% CI, 0.4-8.6], respectively, p Conclusion: Primary refractory PTCL is associated with dismal outcomes. The likelihood of achieving a remission and proceeding to transplant is ≈30% and with transplant, only 11 (19% of patients with primary refractory disease) achieved a durable remission. Improved understanding of resistance mechanisms in PTCL and the development of improved therapeutic strategies are needed. A significant survival benefit was not observed for patients receiving traditional salvage regimens compared to other systemic second-line regimens, with median survival Disclosures No relevant conflicts of interest to declare.