Medical Oncologist and Chief of Memorial Sloan-Kettering Cancer Center's Lymphoma Service
Would you briefly describe Hodgkin lymphoma?
Hodgkin lymphoma is a disease of the lymphoid system. It usually starts in the lymph glands, but it can spread to other organs outside of the lymph system such as the bone, liver, or lung. Hodgkin lymphoma (formerly known as Hodgkin's disease) is a cancer occurring in the younger population where the median age at diagnosis is the late 20s or early 30s.
Hodgkin lymphoma was one of the first cancers to be cured with combination chemotherapy, and it is curable in most cases, even when the disease is widely spread throughout the body.
How common is Hodgkin lymphoma?
Hodgkin lymphoma is a relatively uncommon cancer. This year, it is estimated that 8,000 new cases of Hodgkin lymphoma are diagnosed in the United States.
How is Hodgkin lymphoma typically treated? What chemotherapy regimens do patients with Hodgkin lymphoma usually receive, starting with the low risk?
The treatment for Hodgkin lymphoma depends establishing the diagnosis, extent of disease, and other prognostic factors. A biopsy of the lymph node (or other disease site to which the Hodgkin lymphoma has spread) is needed to diagnose Hodgkin lymphoma. Once a diagnosis is established, the next step is to determine where the Hodgkin lymphoma is located, which is referred to as staging. There are four stages for Hodgkin lymphoma. Stages I and II represent early-stage disease and Stages III and IV represent advanced disease.
The treatment of Hodgkin lymphoma is dependent on stage assignment in addition to prognostic factors, which are mainly used for early-stage disease. If you have Stage I or II, additional prognostic information is needed to make the optimal treatment decision for the patient — prognostic factors.
The most widely used prognostic factor system that drives clinical decisions was reported by the German Hodgkin Lymphoma Study Group. This system assesses four different parameters: presence or absence of bulky disease; elevated erythrocyte sedimentation rate; number of nodal sites; and presence of extranodal disease involvement.
If a patient doesn’t have any of these factors, they are categorized as Stage I or II, favorable or good risk. A patient with any of these factors would be categorized with Stage I or II, unfavorable. Although the term “unfavorable” can sound scary to patients, it is still highly curable. The distinction is made between favorable and unfavorable because the treatment is different for each group.
The standard treatment for favorable or good risk patients is two cycles of combination therapy ABVD (doxorubicin [Adriamycin], bleomycin [Blenoxane], vinblastine [Velban], dacarbazine [DTIC-Dome]), with relatively reduced doses (20 Gy [a Gy is a unit of absorbed radiation]) of radiation therapy. About 95 percent of the patients in this group are cured.
Patients who have unfavorable Stage I or II disease are treated with four cycles of ABVD with slightly higher doses (30 Gy) of radiation therapy. About 85 percent of the patients in this group are cured.
For patients with advance disease—Stage III or IV disease— the most widely used regimen is also ABVD, and patients usually receive six cycles and sometimes radiation therapy at the end, but most of the time radiation therapy isn’t needed.
There is one category in between, which is Stage I or II bulky mediastinal (i.e. within the chest cavity) mass. It is a very common presentation of Hodgkin lymphoma; a young man or woman comes to the office with a large mediastinal mass, sometimes up to 15, 16 centimeters. Even though this would be Stage I or II disease, the patient would be treated with six cycles of ABVD plus radiation therapy.
What are the current main areas of research for Hodgkin lymphoma?
There are two parallel tracks for current research. Although, the cure rate is about 80 to 85 percent for all patients with Hodgkin lymphoma and 85 to 95 percent for patients with early stage nonbulky Hodgkin lymphoma, there’s still room for improvement. The goal of the first track is to improve cure rates and hopefully cure every single patient.
Because Hodgkin lymphoma is a highly curable disease and the patient population is relatively young, once these patients are cured, we want them to live as long as otherwise healthy individuals. There are concerns about long-term delayed side effects of treatment that may impact patients survival. Therefore, the goal of the second track is to decrease the long-term toxicity of the treatment regimens. This research is focused on optimizing treatment regimens without compromising a cure. We are investigating reductions in numbers of cycles of chemotherapy and/or elimination of radiation therapy.
For improving cure rates — and this is applicable for newly diagnosed patients and patients with relapsed disease —new agents are being incorporated into standard combination regimens. The FDA has approved a new drug called brentuximab vedotin (Adcetris), which is an antibody drug conjugate that delivers a toxic drug to the cancer cells while sparing most of the normal cells. Brentuximab vedotin is now being incorporated with frontline chemotherapy regimens. It is also being incorporated with salvage chemotherapy regimens in pretransplant settings, and there are trials investigating the addition of brentuximab vedotin to treatment regimens in the post transplant setting. There are other agents under investigation that are being incorporated into standard treatment regimens. They’re still investigational, but the idea is to incorporate new active agents with a standard regimen.
In terms of reducing toxicity, I described earlier how, in patients with early-stage, favorable disease, reduced cycles of chemotherapy and doses of radiation are used without compromising a cure. That’s a major step forward in the medical field, and there are other attempts to eliminate radiation therapy from the treatment programs using functional imaging.
Can you talk about the importance of clinical trials, and are there any specific trials you wish to discuss?
Because Hodgkin lymphoma is a relatively uncommon and highly curable cancer, it was not high on the radar screens for drug companies. For years there have been no new agents for these patients, although there is a clear unmet medical need, especially in patients with relapsed disease.
Today, there are many new drugs under investigation, but it may be challenging to enroll patients in clinical trials for Hodgkin lymphoma because it is highly curable with the current therapies. It is good to keep in mind that brentuximab vedotin was a drug that was investigated in clinical trials, and many patients benefited from it before it was approved by the FDA. So the purpose of clinical trials is not to experiment on people, but rather to help patients through experimental treatments
Can you talk about some new and emerging treatments for Hodgkin lymphoma?
There are a variety of agents that are showing promise in clinical trials. The leading compounds are the PI3 kinase pathway-directed therapies, including mTOR inhibitors, PI3 kinase inhibitors, and Akt inhibitors; and the HDAC inhibitors.
Right now these agents don’t seem to be on track for single-agent approval strategy by the FDA like brentuximab vedotin, but they are promising for combination therapy strategies. There are trials combining an mTOR inhibitor with brentuximab vedotin in a post-transplant setting and there are plans for a trial combining an HDAC inhibitor with brentuximab vedotin in post-transplant setting.
What advice would you give to a newly diagnosed patient?
Generally, the patients I see who have just been diagnosed with Hodgkin lymphoma are young and their anxiety is high. Frequently, either the patients are engaged or have recently gotten married or they come with their parents; and, of course, the parents are very concerned about their children. My patients have usually done their homework by doing research on the internet or talking to other individuals so they know Hodgkin lymphoma is a curable disease. However they want to be reassured by someone who has experience with treating these patients. They need to know that that even if we find Hodgkin lymphoma cells in their bone marrow, liver, or lung, they still have a very good chance of cure.
Because these patients are young, fertility is often a big issue. I counsel my patients about fertility and also discuss survivorship in the long-term. I explain the importance of follow-up for second malignancies and late effects of the disease, such as cardiotoxicity.
How are you involved with the Lymphoma Research Foundation (LRF)? And why would you recommend that a patient become involved with LRF?
I am a member of the Scientific Advisory Board for LRF. It is an outstanding organization that serves as a bridge between physicians and patients. They also bring physicians and investigators from all around the world together for collaboration on new treatment strategies for patients. I would recommend that patients and caregivers reach out to LRF because it is a reliable, independent, and objective resource for information.
Updated June 19, 2013