What's New In Hodgkin Lymphoma Research and Treatment?
Important research into Hodgkin lymphoma is going on in many university hospitals, medical centers, and other institutions around the world. Scientists are getting closer to finding out what causes the disease and how to improve treatment.
In recent years, PET/CT scans have been found to be very helpful in determining the extent of Hodgkin disease in the body and in assessing how well treatment is working. PET/CT scans are now commonly used early in the course of treatment to help doctors decide how much treatment needs to be given.
In general, cure rates for Hodgkin lymphoma are high, but long-term side effects of treatment are an important issue. A very active area of research is directed at learning which patients can be treated with gentler therapy and which patients need stronger treatment.
A related area of research is finding less-toxic treatments that have fewer serious long-term side effects, yet still cure as many patients as possible. New chemotherapy (chemo) combinations of as many as 10 different drugs are being studied. The reasoning behind this approach is that even though more drugs are needed, using less of each drug might lead to fewer side effects. Another approach is using newer drugs that better target Hodgkin lymphoma cells, as opposed to chemo drugs. Some of these are described below.
The same is true for radiation therapy. Doctors are looking to see which patients (especially children) might do just as well with lower doses of radiation, or even no radiation. Doctors are also studying whether newer forms of radiation therapy, such as intensity-modulated radiation therapy (IMRT) and proton therapy, might be useful for Hodgkin lymphoma. These approaches focus radiation more precisely on tumors, which limits the doses reaching nearby normal tissues.
New chemo drugs and drug combinations are being studied in patients with Hodgkin disease. Some drugs, such as vinorelbine, idarubicin, bendamustine, and gemcitabine, are already used to treat other cancers, and have shown promise against Hodgkin disease that has relapsed after other chemo treatments. Studies are in progress to see if these drugs could be more effective than the ones now in use.
Newer drugs that work differently from standard chemo drugs are now being studied as well. These are known as targeted therapy drugs. Some of the types of targeted drugs that have shown promise against Hodgkin lymphoma in early studies include:
- Phosphatidyl-inositide 3 kinase (PI3K) inhibitors, such as idelalisib and INCB040093
- Janus kinase (JAK) inhibitors, such as ruxolitinib
- mTOR inhibitors, such as sirolimus, temsirolimus, and everolimus
- Histone deacetylase (HDAC) inhibitors, such as panobinostat and vorinostat
Some of these targeted drugs are being studied in combinations, in the hope that they might be more effective when given together. Many other targeted drugs are being studied as well.
Immunotherapy (including monoclonal antibodies)
Immunotherapy is treatment that helps the body’s immune system attack cancer cells more effectively. Newer forms of immunotherapy have shown to be helpful against several types of cancer in recent years, including Hodgkin lymphoma.
Immune checkpoint inhibitors
Immune system cells normally have substances that act as checkpoints to keep them from attacking other healthy cells in the body. Cancer cells sometimes take advantage of these checkpoints to avoid being attacked by the immune system.
Some newer drugs, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), work by blocking these checkpoints, which can boost the immune response against cancer cells in the body. These drugs have shown promising results against Hodgkin lymphoma, even in people who have already had several other treatments. They are now approved for use against Hodgkin lymphoma after other treatments have been tried, and several other checkpoint inhibitors are now being studied as well.
Chimeric antigen receptor (CAR) T-cell therapy
In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on the surface of lymphoma cells. The T cells are then multiplied in the lab and given back into the patient’s blood, where they can seek out the lymphoma cells and launch a precise immune attack against them.
This technique has shown encouraging results in early clinical trials against some hard-to-treat Hodgkin lymphomas. Doctors are still improving how they make the T cells and are learning the best ways to use them. CAR T-cell therapy is only available in clinical trials at this time.
Monoclonal antibodies (mAbs) are man-made versions of immune system proteins. Some can kill cancer cells by themselves. Others have radioactive molecules or cell poisons attached to them, which help kill cancer cells. An advantage of these drugs is that they seem to target lymphoma cells while having fewer side effects than standard chemo drugs. They may be used alone or combined with chemo.
Some mAbs, such as brentuximab vedotin (Adcetris) and rituximab (Rituxan), are already being used to treat Hodgkin lymphoma in some situations. Researchers are now studying if these drugs might be useful in other situations. For example, brentuximab is now being studied to see if it might be helpful earlier in the course of the disease. And studies are now being done to see if rituximab can help treat classic forms of Hodgkin lymphoma as well as the nodular lymphocyte predominant type.
Many newer mAbs are now being studied as well.
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-319.
Bartlett NL, Foyil KV. Chapter 105: Hodgkin lymphoma. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa. Elsevier: 2014.
Younes A, Carbone A, Johnson P, Dabaja B, Ansell S, Kuruvilla J. Chapter 102: Hodgkin’s lymphoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.
Younes A, Sureda A, Ben-Yehuda D, et al. Panobinostat in patients with relapsed/refractory Hodgkin’s lymphoma after autologous stem-cell transplantation: Results of a phase II study. J Clin Oncol. 2012;30:2197−2203.
Last Medical Review: February 10, 2017 Last Revised: March 28, 2017