Melanoma Relapse Treatment
- In cases of melanoma relapse—when the cancer returns after previously being treated—doctors may use a combination of therapies to achieve the best results.
- Therapies targeting LAG-3 (such as Relatlimab) in combination with PD-1 blocking antibody nivolumab show promising results for melanoma relapse. There are also exciting developments forthcoming with tumor-infiltrating lymphocytes (TIL) therapy and new checkpoint inhibitors.
- Despite some challenges in treating melanoma relapse, there are many promising therapies in development.
There are several types of melanoma, and each one requires a different approach to treatment. In cases of melanoma relapse—when the cancer returns after previously being treated—doctors may use a combination of therapies to achieve the best results.Read More
The goal of melanoma treatment is always to rid the body of cancer cells while causing as little damage as possible to healthy tissue. With continued advances in melanoma relapse treatment, more people are beating melanoma and living long, full lives.
Dr. Jeffrey Weber, NYU Langone oncologist and melanoma specialist, spoke with SurvivorNet to share his insights on treating melanoma that has returned after one or two previous treatment regimens.
Potential Melanoma Relapse Treatments
Dr. Weber says that despite some “promising drugs” that have not “panned out” there are still advances in treatments for melanoma that has returned.
Tumor-Infiltrating Lymphocytes (TIL)
TILs are a type of white blood cell that can kill cancer cells. By extracting TILs from a tumor and then growing them in the lab, doctors can infuse large numbers of these cells back into the body to fight cancer.
“The second line idea of choice is going to be tumor-infiltrating lymphocytes,” explains Dr. Weber. He notes that the clinical data from a study of TIL product Lifileucel “looks promising” with a 36% overall response rate (proportion of patients who have a partial or complete response to therapy) in participating patients. FDA approval for the product has not yet been granted.
“The game-changer that could happen as early as the end of this year would be tumor-infiltrating lymphocytes,” says Dr. Weber. He emphasizes that several companies are working on this type of immunotherapy, so there is a good chance that it will become available to patients in the near future.
Nivolumab (Opdivo) plus Relatlimab (RELA)
Experts are still exploring the best ways to use immunotherapy drugs to treat melanoma. Recently, researchers have been studying the potential benefits of using these drugs in combination with each other in a way that reduces toxicity.
Therapies targeting LAG-3 (such as Relatlimab) in combination with PD-1 blocking antibody nivolumab show promising results for melanoma relapse. One study, RELATIVITY-047, showed evidence that the combination led to a higher response rate than nivolumab alone.
Another 2021 study showed the potential of this drug combination for neoadjuvant (given before primary treatment in order to increase the effectiveness of that treatment) and adjuvant therapy (used after primary therapy to improve the chances of disease-free survival). This 30-patient study demonstrated that the combination therapy was able to achieve a 66% pathologic complete response rate in stage 3B and 3C melanoma patients. (Pathological complete response rate means samples reviewed by a pathologist show no remaining cancer cells.)
The Food and Drug Administration granted priority review to this drug combination in Sept. 2021.
Immune Checkpoint Inhibitors
Checkpoint inhibitors are a type of immunotherapy that works by blocking specific proteins (known as checkpoints) on immune cells. This allows the immune system to better attack cancer cells.
There are several different types of checkpoint inhibitors, the most popular being T cell checkpoint inhibitors. These drugs work by blocking the checkpoint proteins CTLA-4 and PD-1.
Dr. Weber notes that there are several new checkpoint inhibitors in the “early phase testing” that show promise for treating melanoma relapse, including the newer macrophage-related myeloid checkpoints. This research may lead to new treatments for melanoma relapse in the future.
Promising Options After Multiple Relapses
Once a patient has progressed to the third line of treatment, their options become more limited. However, Dr. Weber notes that there are many potential therapies worth exploring. (Third line treatment is treatment that is given when both initial treatment (first-line therapy) and subsequent treatment (second-line therapy) don’t work, or stop working.)
Many of the novel second-line treatments being studied for melanoma relapse are also being explored as potential therapies for patients in the third-line setting. Some of these include:
- Adoptive cell therapy: Including tumor-infiltrating lymphocytes (TILs), a type of immunotherapy that uses the body’s own immune system to fight cancer
- Bispecific antibodies: A type of immunotherapy that uses two different antibodies to target cancer cells
- Alternative checkpoints: Another immunotherapy that targets specific proteins other than CTLA-4 and PD-1
Unfortunately, some therapies have yet to show much promise in this setting. “Targeted therapies have been a bit of a disappointment,” adds Dr. Weber. “There have been a couple of ERK inhibitors which have been abandoned, to my disappointment, because they didn’t look very promising.”
The Future of Melanoma Relapse Treatment
Despite the challenges in treating melanoma relapse, there are many promising therapies in development. With continued research, we may soon see many improved treatment options. Researchers are optimistic that less toxic and more effective alternatives are on the horizon.