Treating Hodgkin lymphoma with Immunotherapy

Hodgkin's Lymphoma Cells

Like many types of cancer, Hodgkin lymphoma (HL) continues to present a challenge for medical practitioners and researchers. Although considered treatable, its aggressive tendency to relapse makes it trickier to manage than its more common counterpart—non-Hodgkin lymphoma (NHL). However, the health sciences are determined to not lose in the race as even now, experts are looking to immunotherapy as a possible weapon against HL.

What is Hodgkin lymphoma?

It is one of the two most common types of lymphoma along with NHL, although the latter occurs in more patients. Like NHL, HL also begins as a mutated lymphocyte which, instead of performing its function as one of the body’s safeguards against disease, starts growing and living longer than it should. The mutation spreads and results in more oversized cells accumulating in the lymphatic system and leading the lymph nodes to swell, which is a characteristic symptom of lymphoma.

There are several types of Hodgkin lymphoma. What differentiates it from NHL is the presence of Reed-Sternberg cells in the lymph nodes. These are large, peculiar cells that look like no other cells in the human body. Studies suggest that they originate from mutated B cells although at times, they may also come from T cells.

Nobody knows the exact reason why HL relapses (returns after remission) or becomes refractory (resists primary treatment) but a number of factors have been studied. These include age, the stage of the disease, sex, white blood cell count, and others. Generally, people of advanced age and those with big tumors and multiple nodal sites are at a higher risk of experiencing a relapse.

Treating HL with immunotherapy

Chemotherapy remains as the most prevalent treatment for HL. When cancer cells become too aggressive, there may be a need to increase the dosage of chemo medication, killing more aberrant cells but harming the bone marrow’s healthy cells and impairing its ability to produce healthy blood in the process. As such, chemotherapy is paired with autologous stem-cell transplant (ASCT), where stem cells are gathered from one’s own blood and transplanted back to the body. These blood-making cells help keep the bone marrows functional despite the chemotherapy.

Immunotherapy is a treatment approach that stimulates the body’s own immune system to get rid of existing diseases, even cancer. Experts are looking into two drugs to boost the effectiveness of conventional chemo in treating advanced, relapsed, or refractive cases of Hodgkin lymphoma:

  1. Brentuximab vedotin, marketed as Adcetris, is used to treat relapsed or refractive HL, as well as systemic anaplastic large cell lymphoma (ALCL). It targets cells expressing the CD30 antigen, which is a marker for HL tumors. It acts as an antibody and attaches itself to the tumor cells. It then enters the cells and disrupt their normal functioning, causing them to die. Due to its nature as a targeted treatment, it is noted for causing decreased toxicity to healthy cells.
  2. Nivolumab, known more popularly as its trade name Opdivo, is used to treat several types of cancer, including melanoma and lung cancer. Like Adcetris, nivolumab acts as an antibody by blocking the signals that prevent active T cells from attacking the cancer cells. Once the signal is blocked, the body’s own immune system can eliminate the cancer cells normally.

Studies have so far yielded positive and promising results. According to the latest results of the CheckMate-205 trials, nivolumab had high response levels. A large majority (77%) of the study’s respondents had stage III or higher disease. Among patients who were Adcetris-naïve, the response rate was 65%. This improved with patients who have undergone treatments with Adcetris and ASCT. Those who received Adcetris after ASCT had 68% response rate while those who received Adcetris before and after ASCT had a response rate of 73%. The complete response rate (CR) was 29%, 13%, and 12% respectively.

Michele Fanale, MD, lead author of the study, describes the dosing as “manageable” and something that “patients can continue being on for the rest of their lives.”

What makes this finding such a great news is how Opdivo offers a brighter future for patients who suffer from refractive HL, especially those who have formerly resisted Adcetris. Relapsing and refractory HL presents many difficulties as doctors exhaust means to manage the disease. The effectiveness of Opdivo in addressing relapsed and refractory HL gives doctors additional means to care for their patients on an everyday basis.

Experts are looking into combining Adcetris and Opdivo for better results. This approach is also being considered for senior patients and those with organ issues and other conditions that prevent them from undergoing chemotherapy. Opdivo is also being considered for use with other inhibitors as a way of treating NHL and T-cell lymphoma. This will be one of the subjects of the next phase of the trials.

As Opdivo is a relatively new treatment for lymphoma, researchers have yet to discover the ideal length of time for the treatment. This is a common problem encountered with new treatments, such as when Adcetris was still on the testing phase. Experts are also looking into the role that Opdivo will play in terms of retreatment or the possibility of an allogeneic stem cell transplant, a procedure that is similar to ASCT, but where the stem cells are collected from a donor instead of the patient’s own body.

Dr. Fanale implies that additional tests and trials need to be done to find answers and to ensure that treatment with Opdivo addresses the varying needs of HL patients. What is important though, is that the drug works. It is one that patients can keep taking while living normal lives.

“These patients can go to school or take care of their kids, or go to work, which is very important,” she said.

The possibility of living a life free from cancer is lovely indeed, and developments in pharmaceuticals and medicine are making it more and more possible. There is little doubt that given time, even a disease as terrible as HL will be found a cure that everyone can use and benefit from.

 

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