Professor - Department of Medicine, Division of Hematology/Oncology at UC Irvine Health
Please describe anaplastic large-cell lymphoma?
Anaplastic large-cell lymphoma (ALCL) is a non-Hodgkin T-cell lymphoma of which there are three varieties grouped into two categories (systemic and primary cutaneous). Systemic ALCL is divided into two parts. The difference between the two systemic varieties is that one expresses the anaplastic lymphoma kinase 1 (ALK-1) protein (ALK-positive ALCL) and the other does not express the ALK-1 protein (ALK-negative ALCL). Patients with the ALK-positive form have a better prognosis than patients with ALK-negative ALCL. Both systemic varieties can occur on the skin, lymph nodes, and other internal organs.
The other form is primary cutaneous ALCL; it is generally limited to the skin. Primary cutaneous ALCL is almost always ALK-negative, but different than the systemic ALCLs, this ALK-negative variety has a very good prognosis, tends to recur on the skin, and receives only local therapy. The skin and the systemic disorders are quite different even though they are called the same thing.
How common is ALCL?
ALCL is a rare non-Hodgkin lymphoma, accounting for <1 percent of all non-Hodgkin lymphomas in adults and approximately 20 percent of all T-cell lymphomas in the United States.
How is ALCL typically treated?
The systemic forms of ALCL are commonly treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), a standard combination chemotherapy for T-cell lymphomas. ALK-positive ALCL is often responsive to CHOP and has a good survival rate. For patients with ALK-negative ALCL or high-risk ALK-positive ALCL, the initial CHOP regimen is often followed by an autologous stem cell transplant (in which patients receive their own cells) once a complete response is attained.
For primary cutaneous ALCL limited to the skin, the lesion will disappear without treatment in approximately 30% of patients. If treatment is needed, radiotherapy is most commonly used or the lesion is sometimes cut out. Very, very rarely a patient will have more than one lesion on the skin and require systemic therapy.
What are the current main areas of research and treatment?
For primary cutaneous ALCL, the focus of research is determining ways to distinguish the disease from other cancers that mimic it, including lymphomatoid papulosis and mycosis fungoides. Proper diagnosis is critical for selecting the most appropriate treatment.
Recently there has been a description of women who had breast implants and develop something that looks like anaplastic large-cell lymphoma around the implants; this gives us a window into perhaps pathogenesis or why these lymphomas occur.
Another new drug already approved by the United States Food and Drug Administration for the treatment of patients with relapsed (the disease returns) or refractory (the disease does not respond to initial treatment) ALCL is brentuximab vedotin (Adcetris). This drug was tested in an international randomized trial for people who have CD30-positive skin disorders, including cutaneous ALCL. This area of study is particularly important because even when patients respond to treatment, the disease often returns.
Brentuximab vedotin is also being investigated for administration earlier in the patient’s course rather than waiting for relapsed or refractory disease. In addition, there are many new drugs looking at T-cell lymphomas as a group and that information will often apply to patients with anaplastic large-cell lymphoma as well.
When you discuss treatment options with your patients, do you talk about enrollment in clinical trials?
Absolutely. The clinical trial of brentuximab vedotin is an example of a trial for a new drug for treating ALCL.
How are you involved with the Lymphoma Research Foundation and why would you recommend a patient become involved with them?
I have been involved with the Lymphoma Research Foundation (LRF) since the Los Angeles chapter was founded. At that time, I worked with the Scientific Advisory Committee reviewing grants. Subsequently, I’ve worked more in terms of advocacy and education for patients, and I am very proud to be among the speakers for LRF because they really represent the thought leaders and the people who know the most about lymphomas in the United States and sometimes internationally. LRF organizes these knowledgeable people at a venue to explain things to patients in a way that they can understand, which allows them to advocate for themselves.
Patients should not rely on the pathology report from a faculty that does not specialize in lymphoma. Community practitioners may not appreciate the nuances of a patients presentation or disease. Just because the pathology report says ALCL, that doesn’t really tell you if it is limited to the skin or if it is systemic. LRF can help patients connect with a facility that specializes in ALCL so they can be evaluated by very knowledgeable professionals.
This is important because lymphoma is not the most common cancer in the United States, and though community physicians can certainly treat ALCL, they may not be able to explain the nuances or be aware of all the new and upcoming drugs that are available. These educational programs are a great opportunity for patients to hear state-of-the-art discussions at a level that professionals hear at national meetings.
I urge patients to think about getting a pathology review from a very knowledgeable site and lymphoma program before embarking on treatment.
Updated: January 30, 2013