Cancer in young adults is rare. When it does occur, one of the most common types is Hodgkin lymphoma. Cure rates are high, especially when the disease is detected early. But the standard treatment — usually a combination of chemotherapy and radiation therapy — often results in serious, long-term health problems that can develop 20 or more years after treatment.
Memorial Sloan Kettering’s David Straus, a medical oncologist who specializes in treating blood cancers including lymphoma, is focused on finding treatment regimens that have fewer side effects without compromising success rates.
In December, Dr. Straus presented a study at the American Society of Hematology (ASH) annual meeting that looked at using PET scans to monitor the presence of disease after initial treatment to help with decisions on additional treatment.
We spoke with him recently about that study and his work.
What is the current treatment for Hodgkin lymphoma?
For early-stage disease, we use a chemotherapy regimen called ABVD, which is a combination of four drugs given together. Patients may receive up to six rounds of this treatment and may also get a course of radiation therapy — most commonly to the neck and chest, where many lymph nodes are located. This has been a standard treatment for at least 25 years, and it is effective in treating the disease, as shown by the high cure rates.
Patients who do not respond to or recur after initial therapy may undergo more intensive treatments, including bone marrow or stem cell transplantation using either their own cells or donor cells. This option also offers the possibility of a cure.
If the cure rates are so high, why is it important to find better treatments for this disease?
In our most recent study, the average age of patients we treated was between 25 and 30, which is typical for people with Hodgkin lymphoma. The patients who are cured should be expected to live a long time. However, studies show that 40 years after treatment, only 25 percent of Hodgkin lymphoma survivors [those whose initial cancer was cured] are still alive. Almost all of the deaths are related to late complications of treatment, particularly radiation therapy.
The leading cause of death in Hodgkin lymphoma survivors is secondary cancers, which are usually related to radiation therapy, with an additional contribution of chemotherapy in some cases. Radiation therapy to the neck and chest area also can lead to cardiovascular damage, such as carotid stenosis, a narrowing of the arteries in the neck that can cause strokes; coronary artery disease; and scarring of the heart valves. Weakening of the heart — leading to heart failure — can be caused by both radiation and chemotherapy, and the risks are higher when both are used to treat the lymphoma.
There are other effects that don’t decrease patients’ life spans but can dramatically affect their quality of life, such as neck drop, which is a loss of nerve and muscle function in the neck that prevents a person from being able to lift his or her head.
Tell us about the recent study you presented at the ASH meeting.
This was a multicenter phase II trial that looked at using PET scans as a biomarker to tailor treatment. PET scans are typically used at the end of treatment, and patients who have PET-negative disease — meaning that no cancer can be found on the scan — have a very low likelihood that their disease will come back. PET scans are also currently recommended as a test to monitor how well patients are doing mid-treatment, but we know less about what those findings mean.
In this study, we wanted to find out if interim PET scans — scans given in the middle of treatment — might provide an opportunity to minimize further treatment for some patients, in order to reduce both short- and long-term toxicity. The trial included 164 patients with early-stage disease. All were given PET scans after their second round of ABVD treatment.
The patients in whom the interim PET scan did not detect disease — about 90% — were given two additional rounds of ABVD, for a total of four rounds, and didn’t receive any radiation treatments. Patients who still had evidence of disease on their interim PET scan were given a more intense chemotherapy combination known as escalated BEACOPP, along with radiation therapy.
After an average follow-up time of two years, only eight out of 131 patients who got the less-intensive ABVD-only treatment had relapsed, which is as good as or better than what we would expect to see in patients who receive more prolonged chemotherapy treatment and radiation therapy.
These are still early results, and we’ll continue to follow these patients. But they indicate that a less-intensive treatment approach may provide the same opportunity for patients to be cured with fewer long-term side effects.
Are there other options for patients who don’t respond to standard treatments?
We’re looking at several experimental treatments in clinical trials. There are some newer drugs that appear to be fantastic. One of them is called brentuximab vedotin (Adcetris®). It’s a chemotherapy drug attached to an antibody that targets the cancer more directly by delivering the chemotherapy molecule right to the tumor. It’s already approved by the FDA for disease that fails to respond to or relapses after chemotherapy, but we think it may be effective in treating disease that has not yet been treated or has received less chemotherapy.
We’re also looking at immune therapies, particularly so-called checkpoint inhibitors, which take the brakes off the body’s own immune system and enable it to attack the cancer. We are currently investigating two of these drugs that are already approved for the treatment of other cancers, nivolumab (Opdivo®) and pembrolizumab (Keytruda®), in clinical trials. Our early work has suggested they have very high response rates.
What are the next steps for your research?
For patients who need radiation therapy, we are looking at ways to do it more safely. I’m planning a study with radiation oncologist Oren Cahlon that looks at substantially decreasing the size of the areas treated with standard techniques or using newer, more precise techniques such as proton beam therapy, compared with current radiation therapy programs, to reduce exposure to other organs and tissues that might be damaged and lead to late complications.
It’s sad for me when these patients whose cancer I have treated come back to see me years later and they’re suffering from all these side effects. It is also very frustrating to have cured the Hodgkin lymphoma only to have them die of the complications of treatment. And although the radiation therapy that’s given today is safer than what was used when many of these now-middle aged patients were treated, we think that it could be administered even more safely if it is necessary.
Because of that, I believe that what we’re doing here is important research that could ultimately benefit many patients who are often young and have long lives ahead of them.