Kristie L. Kahl

in 2021, more than 200,000 new cases of melanoma are expected to be diagnosed, according to Aim at Melanoma. For all stages, the survival rates are estimated at 93% — and hope continues to rise among those with the disease as new therapies are under clinical evaluation.

In particular, treatment options that involve patients’ immune systems in attacking malignant cells continue to be expanded upon.

As part of its Speaking Out video series, CURE ® spoke with Dr. Sunandana Chandra, from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University
in Chicago, on behalf of Aim at Melanoma, about emerging therapies in the treatment of melanoma.

Q: Can you talk about what adoptive T-cell therapy is?

A: Adoptive T-cell therapy is a way of treating a person’s cancer with their own immune cells. It requires collecting and growing or expanding a patient’s own T cells. So the way that that’s accomplished is that a piece of the tumor — or melanoma in this case — is surgically removed and then processed at a separate facility or sometimes at the institution’s own facility. It’s processed at a separate location so that these immune cells in the tumor, known as tumor infiltrating lymphocytes, can be extracted and then expanded or grown. And what’s unique about those immune cells is that they have the ability to recognize that person’s own melanoma. So then the patient undergoes chemotherapy, and those expanded
T cells are then infused back into the patient, along with a few doses of this drug called interleukin 2, or IL-2. So that’s essentially what adoptive T-cell therapy is.

Where are we in evaluating these therapies like TIL?

The therapy is logistically a bit more challenging to administer. But this therapy is quite promising. It is important to note that it’s not yet (Food and Drug Administration [FDA]) approved.

What kind of data are we seeing with these therapies?

We are seeing that this is a very promising therapy for patients who have progressed on immunotherapy and/or a BRAF/ MEK therapy if they have a BRAF mutation. And if a patient is well enough to receive TIL therapy, then it is definitely another option for us, the medical oncologist, to consider for a particular patient. Now, not all patients may be eligible for TIL therapy based on certain clinical characteristics and tumor characteristics, but it’s certainly something that we could at least consider.

What do patients with melanoma have to look forward to in the treatment landscape?

In cutaneous melanoma, there’s a lot of new therapies that are being looked at to try to improve the patient’s survival outcomes. Newer agents that are being studied in addition to TIL therapy are ones that target LAG-3, TIGIT — this class of oral drugs called tyrosine kinase inhibitors. And all of these that I just mentioned can be used in combination, we think, with our existing immunotherapy drugs. 

And so that’s being actively studied in clinical trials. And in addition, other options such as immunomodulators, or drugs that tweak or affect the immune system, such as STING agonists, toll-like receptor 9 agonists may also affect the immune system in a positive way that ultimately lead to cancer cell death.

That sounds like a lot to look forward to.

Absolutely, I mean, in general, we are trying to use combination approaches either with our existing FDA-approved drugs or new drugs all together that target different proteins to ultimately try to cause melanoma cell death.

For more news on cancer updates, research and education, don’t forget to 

Articles

In its Speaking Out video series, on behalf of Aim at Melanoma, CURE ® spoke with Dr. Sunandana Chandra about emerging therapies in melanoma.

Aiming for New Targets: Emerging Therapies in Melanoma

Adjuvant and Neoadjuvant Therapy in Melanoma

Immune-Modulating Antibodies for Melanoma Treatment

Emerging Therapies in the Treatment of Melanoma

Uveal Melanoma

Videos

On behalf of AiM at Melanoma, Drs. Jeffrey Farma and Sunandana Chandra discuss current and future treatment options for melanoma, including a rare subtype.

Understanding Treatment Options in Melanoma

After almost five years of follow-up, the addition of Darzalex (daratumumab) to Revlimid (lenalidomide) and dexamethasone reduced the risk of death by 32%, compared with dexamethasone alone in patients with newly diagnosed multiple myeloma who are transplant ineligible, according to updated data from the MAIA trial presented at the 2021 European Hematology Association annual meeting.

“These results strongly support upfront (Darzalex) with (Revlimid) and dexmathasone as a new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma,” Dr. Thierry Facon, professor of hematology in the Department of Hematology at Lille University Hospital in France, said during a presentation of the data. Currently, the standard of care for this patient population is Revlimid and dexamethasone.

The estimated five-year overall survival (the length of time that a patient is alive after diagnosis or treatment; OS) rate was 66.3% in the Darzalex, Revlimid and dexamethasone group compared with 53.1% in the Revlimid plus dexamethasone group, “which will likely lead to a substantial improvement in median OS in this patient population,” Facon said.

Facon noted that the significant progression-free survival (the length of time during and after treatment of a disease that the patient lives without recurrence; PFS) benefit of Darzalex, Revlimid and dexamethasone compared with Revlimid plus dexamethasone was maintained, with a 47% reduction in the risk for disease progression or death. Median PFS was not reached with the addition of Darzalex, compared with 34.4 months with Revlimid plus dexamethasone.

The estimated five-year PFS rate was 52.5% with Darzalex, Revlimid and dexamethasone, compared with 28.7% with Revlimid plus dexamethasone. “These data provide a new PFS benchmark in patients with newly diagnosed multiple myeloma who are transplant ineligible,” Facon explained.

Also of note, Facon added, these PFS and OS results were achieved in a patients aged 75 to 90 years.

In the MAIA trial, the researchers enrolled 737 patients (median age, 73 years) with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation (ASCT) to receive either Darzalex plus Revlimid and dexamethasone or Revlimid and dexamethasone (standard of care), alone, until disease progression or unacceptable side effects.

PFS served as the major focus of the study, with other areas including OS, PFS2 (time from enrollment to second disease progression or death), overall response rate, compete response (the disappearance of all target lesions, CR) and stringent CR and minimal residual disease.

Patients were enrolled in the trial from March 2015 to January 2017.

The overall response rate was 92.9% in patients assigned Darzalex plus Revlimid and dexamethasone compared with 81.6% in those assigned standard of care.

Lastly, there were no new safety signals observed with continuous therapy and follow-up. The most common serious or life-threatening side effects in patients assigned Darzalex plus Revlimid and dexamethasone or those assigned standard of care included low neutrophil counts (54.1% versus 37%, respectively), pneumonia (19.2% versus 10.7%), anemia (16.8% versus 21.6%) and low levels of lymphocytes (16.5% versus 11.2%).

Of note, a lower percentage of serious treatment-related side effects occurred after 24 months, compared with the first 24 months, in both treatment groups.

Results from a recent study strongly support a treatment regimen of Darzalex with Revlimid and dexamethasone as a new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma.

Adding Darzalex to Standard of Care May Improve Survival in Newly Diagnosed Multiple Myeloma

Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore.

“I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series.

On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments.

How have genomics and targeted therapies played a role in head and neck cancer treatment?

Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very specifically treat that cancer in a way that will give us the best chance of getting rid of it and potentially try to limit the side effects related to the treatments. This has become a little bit more common now that the ability to analyze these tumors has become more widely available across the country. But still, the majority of these types of treatment approaches will be in the context of a clinical trial.

Do we have any currently approved targeted therapies for head and neck cancer?

That’s a great question. I think these are kind of different and are emerging all the time. There are ones that are focused on very specific mutations, such as what’s called the BRAF mutation, which is one that can be present in melanoma or certain aggressive cancers, such as thyroid cancer. And other ones will target things like tyrosine kinase inhibitors that have a more focused route to try to combat these tumors. And then there are ones that will be discussed a little later, such as immuno-oncology drugs that focus on the program cell death ligand and the receptor to try to turn the body’s immune system back on. Another example is what’s called Erbitux (cetuximab), which is focusing on a specific receptor on cancer cells, really trying to exploit this particular difference in cancer cells compared with normal tissue to try to give the best chance of getting rid of the tumor, but minimizing the side effects of the treatment.

What role has immunotherapy had in head and neck cancer treatment?

Cancer has a way of almost turning off the local immune system. It blocks many of the local immune responses to it. Normally, the body would say, “Yeah, that’s not part of our normal tissue, we want to get rid of it.” And some cancers have a way of blocking that. These immunotherapies have a way of almost inhibiting that blockage, if you will, or turning the immune system back on and allowing your own body’s immune system to fight these tumors. These can be incredibly effective. The challenge is if they’re only effective in a small minority of cancers. And so, when they do work, they can work extremely well and can give really good and long-lasting results. But in a high percentage of patients, the responses are much more modest or (patients) may not even respond at all.

Can you discuss the currently available immunotherapies for head and neck cancer?

There are two. Opdivo (nivolumab) is one that can be used in patients who have not responded or progressed despite standard therapy, including recent treatment with chemotherapy, including cisplatin. And then Keytruda (pembrolizumab) is another similar amino therapy that can be used and has actually achieved approval for use in the primary setting. When cancer comes back in an area that can’t be treated with either definitive surgery or definitive radiation therapy, you can use that as a next avenue for treatment. These are the two (Food and Drug Administration)-approved drugs that are out there. They also have ongoing studies where they’re being combined with other standard-of- care, primary treatments for head and neck cancer. I think in the next five to 10 years, they’ll likely be integrated much more on the front end of cancer therapy, rather than just offering them to those who don’t have other treatment options.

How do clinical trials help to advance these therapies, and why should patients consider joining one?

These are really what allows us to make our cancer treatment better. We constantly are. It’s not just going out and experimenting on people but, rather, we’re comparing these treatments to see how we can improve on the current standard approach to therapy. If you were to look back 50 to 60 years ago, all we had were big, morbid surgeries that people were put through and possibly adding radiation therapy. And then we added cisplatin, which is a drug that can be effective in enhancing the effects of radiation therapy. Now, as we add these other treatments, such as immunotherapy and other targeted therapies, the only way we know if they have any advantage over what we have to offer, currently, is to compare them in a clinical trial.

And with these clinical trials, those who have designed them have been very thoughtful in trying to do so in a way that compares them and then looks to see: Does that give us a benefit in getting rid of the cancer or curing the cancer, or at a minimum, slowing it down or giving a longer life? And/or does it give better quality of life or reduce the level of side effects? That’s what many of these clinical trials are. Some are adding new agents to see if those work better than other ones. For example, in the HPV-related cancer, some of the clinical trials are saying these respond fairly well to treatment. Can we actually back off on the severity of treatment, give them just as good of a cancer cure but (with) fewer long-term side effects? I think they’re critical as the only way we’re going to figure out how best to manage these types of cancers.

On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future.

Kristie L. Kahl

Aiming for New Targets: Emerging Therapies in Melanoma

Understanding Treatment Options in Melanoma

Adding Darzalex to Standard of Care May Improve Survival in Newly Diagnosed Multiple Myeloma

‘On the Rise:’ Immunotherapy Options for Head and Neck Cancer

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