A Conversation About Anaplastic Large-Cell Lymphoma With Steven M. Horwitz, MD

Assistant Attending, Lymphoma Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center

Please describe anaplastic large-cell lymphoma (ALCL).

The term “ALCL” describes three varieties of T-cell cancers. Two of these are systemic varieties: one expresses the anaplastic lymphoma kinase 1 (ALK-1) protein and is referred to as ALK-positive ALCL; the other does not express the ALK-1 protein and is ALK-negative ALCL. Both are systemic, in that they usually first appear in lymph nodes and can then develop in other parts of the body.

The third form is called primary cutaneous ALCL, which looks identical to the systemic ALCL varieties under the microscope but tends to show up first in the skin and often only in the skin. Unlike the systemic varieties of ALCL, primary cutaneous ALCL tends to have a very indolent course, which means it tends to grow slowly. It usually does not make people sick. Although it is not typically dangerous to one’s overall health, it tends to recur.

How common is ALCL?

It is the third most common T-cell lymphoma in the United States, which means it is very uncommon. In the United States, there are about 6,000 to 9,000 people newly diagnosed with T-cell lymphoma each year; approximately 10% to 15% of those people have ALCL.

How is ALCL typically treated?

Both ALK-positive and ALK-negative ALCL are potentially curable using combination chemotherapy. The most commonly used treatment approach has been a regimen called CHOP, which is a combination of three chemotherapy drugs—cyclophosphamide, doxorubicin, and vincristine—and a steroid called prednisone.

People with ALK-negative ALCL have a lower chance for a cure than those with ALK-positive ALCL—although some ALK-positive patients have adverse factors that also lower their chance for a cure. Many attempts have been made to improve the chance for a cure for such patients. Frequently these attempts include stronger chemotherapy regimens such as adding high-dose chemotherapy and a stem cell transplant, often using a patient’s own stem cells, to the end of the initial chemotherapy treatments to try to improve the chance that the ALCL will go away and never come back.

Primary cutaneous ALCL is treated like other skin lymphomas. The treatment paradigm for primary cutaneous ALCL is complicated and, like other skin lymphomas, focuses on milder treatments but ultimately depends on the number of skin lesions and how they change over time.

When you discuss treatment options with your patients, do you talk about enrollment in clinical trials?

Yes. Currently there are no well-established therapies specifically for the systemic ALCL varieties. The use of CHOP, for example, is a strategy that was borrowed from the more common aggressive B-cell non-Hodgkin lymphoma varieties. Clinical trials are essential for developing new drugs that specifically target the T-cell lymphomas, and for understanding how, and how well, those drugs work.

What are some newer treatment options for ALCL and what is on the horizon?

There have recently been three new drugs approved for ALCL: brentuximab vedotin (Adcetris), pralatrexate (Folotyn) and romidepsin (Istodax). Romidepsin is approved for the range of cutaneous and systemic T-cell lymphomas, and pralatrexate is also approved for the majority of T-cell lymphomas, which includes ALCL.

Brentuximab vedotin was recently approved for treatment of systemic ALCL after failure of initial therapy. It specifically targets CD30, which is a protein on the surface of almost all ALCL tumor cells. This has been shown to be very effective for the two systemic ALCL varieties in the relapsed setting, with more than 80% of people showing significant tumor shrinkage. Right now researchers are looking at how to incorporate brentuximab vedotin into people’s initial chemotherapy, to try to increase the chance that people are cured.

Crizotinib (Xalkori) is an ALK inhibitor used for certain types of lung cancer that is just now being studied in ALK-positive ALCL. However, the majority of people with ALK-positive ALCL are already cured with CHOP and with the introduction of brentuximab vedotin in combination with CHOP, the population of people with relapsed ALK-positive ALCL who need more therapy may become quite small in the near future. Nonetheless having too many effective treatments to choose from would be a great problem to have.

Recently we have seen updated data from a large European study of high-dose therapy and stem cell transplant as initial therapy for people with T-cell lymphoma. In that study, the patients with ALK-negative ALCL did quite well. The best ways to incorporate these newer treatment strategies into current treatment approaches, in order to increase the cure rate for people with ALCL, are exciting new areas for research.

How are you involved with the Lymphoma Research Foundation (LRF)?

My main involvement with LRF has been with educational programs, including live presentations and web-based activities. LRF is also a great resource for patients to learn about clinical trials. I work with LRF to help people know what trials are enrolling at my institution and elsewhere, so people can either find experts for second opinions, or find access to new therapies.

Would you recommend that a patient become involved with LRF?

Yes. LRF is very focused on important issues for lymphoma patients and on patient advocacy. It is very important to be able to get good information—from professional information about the disease and treatment options, to where to find expert centers for treatment—and to interact with other people who may be going through a similar situation. Many people, including doctors, may be unfamiliar with ALCL because it is a rare disease. In this situation, I think it can feel like you are alone with your disease, and it can be difficult to get good information. It can really be comforting to find good, reliable information and to connect with people going through the same experience. I think LRF provides this for patients. For example, they have a new website that focuses specifically on ALCL, which is very useful—it has been hard for patients with newly diagnosed ALCL to get good information because this is a fairly rare disease.

Updated: June 20, 2012