Treating T Cell Lymphoma: New Therapies and Strategies Through Clinical Trials

By Steven M. Horwitz, MD  |  Thursday, October 17, 2013

The T cell and natural killer (NK) lymphomas are among the most challenging diseases we treat at Memorial Sloan Kettering. These uncommon illnesses can be difficult to diagnose, and patients too often have inadequate responses to chemotherapy.

Patients with certain subtypes such as mycosis fungoides, other cutaneous T cell lymphomas, and nasal NK/T cell lymphomas often require a multidisciplinary individualized approach, with input from our experts in dermatology and radiation oncology, to ensure optimal treatment planning and delivery.

In recent years, important new drugs have become available. Pralatrexate and romidepsin are now routinely used in the relapsed setting for a broad range of T cell lymphomas. Brentuximab vedotin is available for relapsed anaplastic large cell lymphoma.

However, even as we have added therapeutic options, many questions remain:

  • Which of these new drugs is the best choice for which patients?
  • When is CHOP inadequate for initial therapy?
  • What are the best approaches for cutaneous T cell lymphomas (CTCLs)?
  • Which subtypes of peripheral T cell lymphoma (PTCL) require a unique approach?
  • Who should receive stem cell transplantation, and when is allogeneic transplantation preferred over autologous transplantation?

Despite the addition of new agents, patients still frequently either relapse after treatment or do not respond adequately.

Novel approaches are needed.

Consultation Services

Members of our Lymphoma Service are focused on the treatment of these uncommon diseases with an emphasis on developing new therapies and strategies through clinical trials. We offer a full rage of consultation services for patients with T cell lymphomas, including a dedicated Cutaneous Lymphoma Clinic where oncologists, dermatologists, and pathologists participate in new visits to provide a comprehensive plan.

Our portfolio of clinical trials is aimed at developing the most promising agents for T cell lymphomas and incorporating new agents into novel approaches. The long-term goal is to improve standards of care and create better outcomes for our patients.

Current Clinical Trials

Clinical trials currently open for enrollment include two that incorporate new agents into the upfront treatment of patients with systemic T cell lymphomas:

  1. A randomized study adding brentuximab vedotin to standard chemotherapy for untreated CD30+ T cell lymphomas to test if this strategy is superior to standard CHOP.
  2. A maintenance study of pralatrexate for responders at risk of relapse after standard combination chemotherapy to see if maintenance as part of initial therapy can prolong progression-free survival.

We also have two early-phase studies to identify novel nonchemotherapeutic agents and approaches for patients with relapsed T cell lymphomas (including CTCL).

  1. A phase I/II study combining romidepsin and lenalidomide to study this nonchemotherapeutic regimen for patients with relapsed disease.
  2. A phase I/II study of an oral P13 kinase delta and gamma inhibitor, IPI-145. This is the first study to test this novel P13 kinase inhibitor in patients with hematologic malignancies.

Late-phase studies to definitively evaluate the role of preliminarily promising agents for patients with relapsed disease include the following:

PTCL:

  1. A phase III study of the anti-CCR4 antibody mogamulizumab versus standard therapies for HTLV-1 associated lymphomas. Approved in Japan for ATLL, this study will look at the activity of mogamulizumab in Western patients with ATLL.
  2. A phase III study of the oral aurora kinase inhibitor alisertib versus standard therapies for mature T cell lymphomas. This study seeks to validate the preliminary promising activity of alisertib in PTCL. Enrollment is anticipated to open in November 2013.

CTCL:

  1. A phase III study of brentuximab vedotin versus standard therapies for cutaneous anaplastic large cell lymphoma or mycosis fungoides. This study seeks to extend the preliminary positive experience of brentuximab vedotin in CD30 expressing CTCL.
  2. A phase III study of the anti-CCR4 antibody mogamulizumab vs standard therapies for mycosis fungoides and Sezary syndrome. This study seeks to validate the preliminary promising activity of mogamulizumab in mycosis fungoides and Sezary syndrome.

For more information on these trials or to refer a patient, contact Dr. Horwitz at 212-639-3045.