Pralatrexate Is Effective as Second-Line Treatment Following Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (CHOP) Failure In Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL) (2010)

Abstract Abstract 4882 Background: The most common therapy for first-line treatment of peripheral T-cell lymphoma (PTCL) is cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP). However, most patients progress within 6 to 12 months and there is no standard of care for second-line treatment. Despite a paucity of data in PTCL, B-cell lymphoma salvage regimens are regularly employed as a second-line treatment for PTCL. Pralatrexate was granted accelerated approval in the United States for the treatment of patients with relapsed or refractory PTCL, based on the results of the pivotal study, PROPEL (Pralatrexate in Patients with Relapsed Or Refractory Peripheral T-cell Lymphoma). All patients in PROPEL had received at least 1 prior therapy for PTCL, with a median of 3 prior systemic therapies (range 1 to 12). The objective response rate (ORR) was 29% (by central review) and 39% (by investigator assessment), with a median duration of response (DoR) of 8.1 months (by investigator) and 10.1 months (by central review). The present analysis was conducted to assess the efficacy of pralatrexate as a second-line treatment post-CHOP. Methods: Of the 109 patients who were treated with pralatrexate and evaluable for efficacy in the PROPEL study, a subset of 15 patients received pralatrexate (30 mg/m2 intravenously weekly for 6 of 7 week cycles) as their second-line treatment post-CHOP. Results: The demographics and disease characteristics of the 15 patients treated with pralatrexate in the second-line setting post-CHOP were reflective of the overall PROPEL patient population. Nine of 15 patients (60%) were male. Median age was 60 years. Eleven of the 15 patients had a prior response to CHOP (7 CR and 4 PR). The additional 4 patients had 1 SD and 3 PD, respectively. A summary of pralatrexate efficacy as second-line treatment post-CHOP is presented in the table below. CR=complete response; CRu=complete response unconfirmed; PR=progressive disease; SD=stable disease; PD=progressive disease; DoR=duration of response; PFS=progression-free survival; OS=overall survival. The 15 patients treated in second-line post-CHOP received a median of 16 doses of pralatrexate, for a median of 134 days. Only 1 patient had a grade 4 adverse event (AE) (sepsis) and the only grade 3 AEs to occur in &gt;1 patient were thrombocytopenia (4 patients), and mucosal inflammation (3 patients). Two patients discontinued treatment with pralatrexate due to AEs. Two of the 15 patients remained on treatment (time on treatment = 12.9 and 18.5 months) and in response as of the data cut-off (August 2009), and their DoR data were censored. An additional 2 patients proceeded to stem cell transplant (SCT) after response to pralatrexate, and thus were censored for DoR (at 2.3 and 3.3 months). These 2 patients remain in CR and their current disease-free period (DoR: pralatrexate + SCT) is 20.1 and 21.7 months. The PROPEL study also collected information on response to therapies administered prior to study entry. Of note, 33 patients received combination chemotherapy as their second-line systemic treatment post-CHOP (ICE and DHAP being the most common regimens): the ORR for combination therapy was 33% and the median duration on treatment for responders was 4 months, which is substantially shorter compared with the DoR to pralatrexate (median 12.5 months, per investigators assessment). Conclusions: Pralatrexate administered as second-line treatment (post-CHOP) to patients with PTCL demonstrated high activity with durable responses, including CRs leading in some patients to SCT. Pralatrexate efficacy and safety profile compared favorably with combination chemotherapy in this disease setting. Taken together, this data suggests that pralatrexate is a highly effective, single-agent, second-line therapeutic option for patients with PTCL, including those who are candidates for bone marrow transplantation. Disclosures: Shustov: Allos Therapeutics, Inc.: Honoraria, Research Funding. Pro: Allos Therapeutics, Inc.: Research Funding. Gisselbrecht: Allos Therapeutics, Inc.: Research Funding. Lechowicz: Allos Therapeutics, Inc.: Consultancy; Celgene Corporation: Consultancy. Zain: Allos Therapeutics, Inc.: Speakers Bureau. Furman: Allos Therapeutics, Inc.: Research Funding. Fruchtman: Allos Therapeutics, Inc.: Employment. Horwitz: Allos Therapeutics, Inc.: Consultancy, Research Funding. O'Connor: Allos Therapeutics, Inc.: Research Funding.