Current and upcoming treatment approaches to common subtypes of PTCL (PTCL, NOS; ALCL; and TFHs)

Abstract

The treatment of common nodal peripheral T-cell lymphomas (PTCLs), including PTCL, not otherwise specified (PTCL, NOS), anaplastic large-cell lymphomas, and T-follicular helper lymphomas, is evolving. These entities are currently treated similarly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) for CD30-negative diseases, or brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (CHP) for CD30-positive diseases, followed by consolidation with autologous stem cell transplantation in the first remission. Ongoing improvements in PTCL classification, identification of predictive biomarkers, and development of new targeted agents will lead to more specific therapies that address the unique biologic and clinical properties of each entity. For example, widespread efforts focused on molecular profiling of PTCL, NOS is likely to identify distinct subtypes that warrant different treatment approaches. New agents, such as EZH1/2 and JAK/STAT pathway inhibitors, have broadened treatment options for relapsed or refractory diseases. Furthermore, promising strategies for optimizing immune therapy for PTCL are currently under investigation and have the potential to significantly alter the therapeutic landscape. Ongoing frontline study designs incorporate an understanding of disease biology and drug sensitivities and are poised to evaluate whether newer-targeted agents should be incorporated into frontline settings for various disease entities. Although current treatment strategies lump most disease entities together, future treatments will include distinct strategies for each disease subtype that optimize therapy for individuals. This movement toward individualized therapy will ultimately lead to dramatic improvements in the prognosis of patients with PTCL.

Graphical abstract

Figure 1.

Current frontline treatment for common nodal PTCL. Treatment of patients with nodal PTCL eligible for curative therapy. In the absence of a clinical trial, patients with ALCL and CD30-positive PTCLs receive induction therapy with BV-CHP. Patients with CD30-negative PTCL receive CHOEP (if eligible for intensive therapy) or CHOP. We offer consolidation with ASCT in the first CR for fit patients with higher-risk ALK-positive ALCL (International Prognostic Score of ≥2) and those with other common nodal PTCL entities.

Figure 2.

Potential future frontline induction therapy for common nodal PTCL. Future treatment of common PTCLs should recognize numerous distinct entities and appropriately incorporate novel agents to optimize the therapy for each individual. Alternative treatment approaches may be appropriate for subtypes associated with poor prognosis such as TP53-mutated or CDKN2A-deleted PTCL, NOS, TP63-rearranged ALCL, and DNMT3A–mutated TFH lymphomas. Hypothetical strategies are shown that integrate targeted agents based on biologic features or known drug sensitivity for disease subtypes.