Progress in the Treatment of Peripheral T-Cell Lymphomas: An Orphan No More
Until recently, PTCL has been treated similarly to their B-cell counterparts, with the exception of anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphomas, which has a significantly higher cure rate with CHOP-like regimens; however, optimal therapeutic strategies for most patients with PTCL remain to be defined. The inferior outcomes of the most commonly used treatment option, CHOP/CHOP-like regimens, underscore the need for novel therapies and continued discovery of the molecular and genetic basis of PTCL. Therefore, in most instances, enrollment in a clinical trial has been an initial therapeutic consideration and is reflected in National Comprehensive Cancer Network guidelines.
Because PTCLs are relatively rare, no randomized trials have been performed comparing various therapies; thus, CHOP has remained a suboptimal standard. Either auto-hematopoietic or allo-hematopoietic stem cell transplant, after first remission, is employed in relatively younger patients who are anticipated to withstand transplant-related toxicities. In this volume of the journal, Khan and Cheson have provided a timely review of recent progress in the development of novel agents for PTCL.4 The field has been driven by the need to discover the analog to rituximab that helped to revolutionize the current treatment paradigm for aggressive B-cell lymphomas, that is, RCHOP. Furthermore, from a regulatory and therapeutic management perspective, PTCL has been an orphan disease without a Food and Drug Administration (FDA)–approved indication until 2009.
It is remarkable that between 2009 and 2011, 3 novel agents have now been FDA approved for the management of relapsed/refractory PTCL. These include pralatrexate (September 2009), romidepsin (July 2011), and brentuximab vedotin (August 2011). The FDA approval of pralatrexate represented a major milestone because it was the first agent approved for PTCL. It is an antifolate designed to be more efficiently internalized by the reduced folate carrier. This approval was based on an overall objective response rate observed in a single-arm phase II trial.5 In the PROPEL trial, 109 evaluable patients received pralatrexate at a starting dose of 30 mg/m2 administered as an intravenous push over 3–5 minutes once weekly for 6 weeks followed by a 1-week break (1 cycle). In addition, each patient received vitamin B12 (1.0 mg intramuscular injection) every 8–10 weeks and a daily administration of folic acid (1.0–1.25 mg, orally). Responses were assessed by an independent central imaging review committee using the International Workshop Criteria for malignant lymphoma.
The overall response rate (complete response plus complete response unconfirmed plus partial response) was 27% (95% confidence interval: 19%–36%).