® magazine, has been with the team since October 2020 and has covered health care in other specialties before joining MJH Life Sciences. She graduated from Emerson College with a Master’s degree in print and multimedia journalism. In her free time, she enjoys buying stuff she doesn’t need from flea markets, taking her dog everywhere and scoffing at decaf.

Darlene Dobkowski, MA

TIL therapy is on the rise in melanoma, with potential for other tumor types.

Katie Ortman Doble was 31 years old when she was diagnosed with ocular melanoma, a rare type of cancer that originates in the eye, in May 2013. Since the cancer was contained to her eye, she underwent plaque therapy, a type of radiation therapy, and a biopsy to assess the disease further.

“I received a phone call a few weeks later letting me know that my cells were the best-case scenario,” Doble, now 43 and living in Denver, tells CURE. “They were classified as 1A, which meant there was a less than 2% chance that they would ever spread. So, I thought that was it.”

Her doctor advised Doble to undergo imaging every six months. Doble had clear images in April 2014. But in November 2014, imaging showed that there were at least 12 suspicious lesions on her liver. A biopsy needed to be done immediately.

The biopsy confirmed that she had stage 4 incurable cancer, and her oncologist told her she had 16 months to live. With limited options based on her disease’s genetic makeup, Doble’s father helped her find a clinical trial to participate in. This led Doble, her father and her fiancé across the United States to participate in multiple clinical trials and traditional therapies from January 2015 to mid 2018. She was eliminated from each trial due to side effects or tumor growth, but liver embolization, which is only Food and Drug Administration (FDA)-approved for metastatic colon cancer, stabilized her liver for several years.

After tumor growth in her liver was noticed in June 2020, she was connected with a doctor at the University of Pittsburgh Medical Center’s Hillman Cancer Center, who was conducting a trial in tumor-infiltrating lymphocyte (TIL) therapy.

“The way that the doctor described it was that he was essentially going to wipe out my immune system with chemotherapy, like you would wipe out a computer, then you reinstall the programs. He was then going

to reinstall this cancer that was taken out of my body and programmed like a robot to go back in and attack itself,” Doble says.

Doble underwent tumor banking in July 2020. The TILs were manufactured, and she underwent preparatory lymphodepleting chemotherapy, TIL infusion and high-dose interleukin-2 (IL-2) in September 2020.

“Every scan that I had, we were seeing really, really good results,” Doble says. “My doctor — he kept calling it a bumper crop of cells, like I had one of the largest batches of cells he’d ever grown before.”

Some tumors were disappearing, Doble adds, but one tumor on her liver kept growing. So, in September 2021, she and her husband flew back to Pittsburgh to have half of her liver removed.

“I woke up from that surgery, [my husband] Nick was sitting in the corner, and he was like, ‘He got it all. You have no evidence of disease,’” Doble recalls. 

“It was a miracle day. I have had no evidence of disease for over three years now.”

Amtagvi (lifileucel) was the first TIL therapy approved by the FDA, in February 2024, for the treatment of patients with advanced melanoma whose disease progressed on or after anti-PD-1/PD-L1 therapy and targeted therapy.

“In the past, we only had immunotherapy and targeted therapy as standard options for these patients,” Dr. Sunandana Chandra, associate professor of medicine at Northwestern University Feinberg School of Medicine in Chicago, says in an interview with CURE. “Now we have not only another option, but an option that is very different from the existing approved regimens for metastatic melanoma.”

Chandra adds that this new treatment still has benefits and risks associated with it.

“The upside with TIL therapy is that it’s this novel, first-in-its-class approval [for] metastatic melanoma, where we’re using the patient’s own immune cells against the cancer,” she says. “The downside of TIL therapy is that it’s a rigorous regimen. It requires a huge commitment

from the patient. It is only able to be given in a very limited number of sites across the country.”

Another barrier to TIL therapy is the cost. According to a post on the National Cancer Institute’s website, the manufacturer of Amtagvi noted that a single treatment would cost $515,000, although the company said that financial assistance programs will be established for patients.

“[TIL therapy] is a therapy that, if it is effective, it’s a one-time treatment,” says Dr. Adam J. Schoenfeld, thoracic medical oncologist, and cellular therapist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York. “So, you don’t have to have repeated treatments down the road.”

Patients who may be eligible for TIL therapy are those with advanced melanoma whose disease either progressed on or responded poorly by way of side effects to PD-1 antibody-based therapy, predominately Opdivo (nivolumab) or Keytruda (pembrolizumab). Given the rigor of TIL therapy, patients whose tumors have BRAF mutations are required to have disease progression after targeted inhibitor therapy prior to TIL therapy since targeted inhibitor therapy is less rigorous for patients.

Performance status is another assessment that is taken into consideration when determining whether a patient is a candidate for TIL therapy. This status factors in how functional a person is in their daily life, strength, time spent out of bed or a chair, and daily activities, among other factors. Care teams also assess each organ’s function — particularly the kidneys, heart and lungs.

Once a patient is considered eligible to undergo TIL therapy, the first step is surgery, during which a piece of the tumor is removed to obtain the material needed to make the T cells.

After tumor resection, the patient can return home, and the manufacturing period begins for the TIL product, which is done in an off-site facility. During this time, a patient may undergo bridging therapy or another treatment.

“In the lab, that tumor specimen that was obtained from the patient is then essentially chopped up, and the patient’s own T cells are extracted from it,” Chandra says. “Those T cells have been grown in the lab [and] — about three to four weeks later — are ready to be infused back into the patient.”

Before the TIL cells are infused, the patient undergoes lymphodepleting chemotherapy for five to seven days.

“Normally, we think about chemotherapy as a way to kill rapidly growing cancer cells,” Schoenfeld says. “But here, we’re actually using chemotherapy as a way to reset the clock on your immune system and create space for the TIL to grow when we infuse the TIL.”

After the lymphodepleting chemotherapy is completed, the patient receives the
TIL infusion in the hospital through a vein. During this time, experts say that patients receive up to a trillion T cells that were grown in the laboratory. A patient undergoing TIL is then closely monitored by their care team.

Following that, the patient is treated with high-dose IL-2, boosting the immune system in cancer therapy. This regimen is administered for up to six doses and may take a few days to complete.

“This [IL-2] is what is used to grow the TIL,” Dr. Amod Sarnaik, professor of cutaneous oncology and immunology at Moffitt Cancer Center and the University of South Florida in Tampa, Florida, tells CURE. “So, the thought is that if you just give the TIL without the [IL-2] ... that abrupt withdrawal may cause some problems for the TIL because they’re used to being grown in the high concentration of the [IL-2].”

This entire process, from tumor harvesting to completion of high-dose IL-2, experts say, can take between six and eight weeks. Toward the end of the process, usually after receiving high-dose IL-2, a patient can be discharged home if deemed appropriate. The patient then undergoes subsequent scans in an outpatient setting for care teams to determine whether the TIL therapy had an effect on the cancer.

Jamie Troil Goldfarb, now a 47-year-old living in Takoma Park, Maryland, with her husband and 14-year-old son, was diagnosed with stage 2B melanoma in 2007. The 32-year-old, at that time, underwent surgery to remove it, and a sentinel lymph node biopsy showed clear results. After Goldfarb experienced several infections, her oncologist called the surgeon and urged him to investigate further to see whether a suture was left behind. During that surgery in December 2009, it was discovered that she had stage 3 melanoma, for which a wait-and-watch approach was suggested.

In January 2011, three months after Goldfarb gave birth to her son, Kai, her oncologist recommended she undergo a scan before she returned to work from maternity leave. That is when she learned that the cancer had metastasized to her liver and pancreas, marking her disease as stage 4, and her care team gave her a 15% chance of survival.

With her experience in patient recruitment for a company that conducted clinical trials, she knew immediately to look for options. She found a study assessing TIL therapy in melanoma, for which she was eligible.

Compared with the FDA-approved regimen with Amtagvi, Goldfarb received four full rounds of IL-2 before receiving the lymphodepleting chemotherapy and then the TIL infusion in September 2011. This TIL infusion was somewhat different from Amtagvi, as researchers took Goldfarb’s cancer cells and genetically engineered them to express IL-12 upon contact with the tumor.

Initially, months after the infusion, scans showed that her tumor was growing, which led the research team to consider other treatment options, although Goldfarb was not ready to do that. “I was very emotionally [invested in] this really intense clinical trial for TIL and then being cured,” she recalls.

In January 2012, her scans started to show that the tumors were shrinking.

“All of the tumors shrank over the next two years until I had no evidence of disease, and it’s been 12 years now, completely disease-free,” Goldfarb says. “My diagnosing physician told me that he would do everything in his power to buy me six months with the baby, and [Kai] just turned 14 last week.”

Most of the side effects of this regimen may be associated with the lymphodepleting chemotherapy before the TIL infusion and the high-dose IL-2 after the infusion.

“I got a rash from the chemotherapy, and I couldn’t take steroids,” Doble recalls. “That was really uncomfortable. The TIL experience, it was a 22-minute infusion. It was totally uneventful. And then once the IL-2 hit, that’s when it kind of went downhill. ... [My doctor] was thrilled that I felt like s---. He’d come in and he’d be like, ‘This is good, Katie. This is so good because it means you’re responding.’”

Side effects associated with Amtagvi, according to the FDA, include fever, chills, tachycardia (abnormally fast heart rate), fatigue, febrile neutropenia (fever with a low level of certain white blood cells), diarrhea, rash, edema (swelling from fluid buildup in tissues), low blood pressure, infection, hair loss, shortness of breath and abnormally low oxygen levels.

“The TILs are designed to attack the tumor, but remember, the tumor came from our own cells, so the tumor and normal tissues sometimes share similar targets,” Sarnaik says.

Goldfarb mentions that she got vitiligo as a potential result of the TIL therapy, but other than that, she did not experience any other long-term side effects.

“I got [vitiligo] as an initial side effect around my neck,” she says. “And then five years ago, it [spread]. ... So now it’s everywhere, which is fine. ... I’d rather have vitiligo than cancer.”

With the high-dose IL-2, experts say that side effects can be “somewhat profound in the short term,” Schoenfeld says. This response, he adds, is because IL-2 stimulates the immune system, so it may cause shaking chills, fever, capillary leak syndrome (when fluid leaks outside of blood vessels and into legs and arms), and fluid around the lungs, causing shortness of breath.

Experts say that after a month or couple months after receiving TIL, patients typically regain their strength.

Melanoma was one of the first cancers to be assessed in TIL therapy trials because of how heavily mutated it can present, experts say. Researchers are currently seeing whether TIL therapy can derive similar success in cancers that are also heavily mutated, such as lung cancer.

Studies are also focusing on the potential of TIL therapy in cancers caused by viruses, such as cervical cancer and head and neck cancer. Experts note that cancers with unstable DNA repair mechanisms, such as colorectal cancer, may also see success with TIL therapy. Research is also aimed at assessing TIL therapy in patients with aggressive cancers with minimal treatment options, such as gastrointestinal malignancies and sarcoma.

In addition to assessing the potential benefit of TIL therapy in other cancer types, researchers are aiming to see how TIL therapy itself
can be improved and expanded. For example, researchers are seeing whether there are more effective ways to manufacture TIL, such as identifying TILs that could be expanded or engineering TILs to make them more active. Additionally, researchers are investigating whether there is a way to manufacture TILs so they have other properties to potentially eliminate the need for chemotherapy before or high-dose IL-2 after the treatment.

Goldfarb says she “screams the praises of TIL every chance I get.”

“Every time [my son, Kai,] has a birthday, I think about how lucky I am that I get to see it,” she says.

For more news on cancer updates, research and education,

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Articles

Ocular melanoma patient Katie Ortman Doble's journey highlights the potential of tumor-infiltrating lymphocyte (TIL) therapy in treating advanced melanoma. Despite initial setbacks, Doble achieved no evidence of disease after undergoing TIL therapy, which involves using a patient's own immune cells to target cancer. The FDA approved Amtagvi (lifileucel) as the first TIL therapy for advanced melanoma in 2024. While promising, TIL therapy is rigorous, costly, and limited to select sites. Research is ongoing to expand TIL therapy's application to other cancer types and improve its efficacy.

Empowering the Immune System

Our longtime editor-in-chief offers advice to his successor while discussing the news and education CURE magazine provides for patients with cancer, families and caregivers.

Discussing the Mission of CURE With Our Former and New Editors-In-Chief

The new editor-in-chief of CURE, Dr. Joshua K. Sabari, recently sat down for a wide-reaching conversation with his predecessor, Dr. Debu Tripathy, to discuss their vision for CURE, how cancer care has evolved over the years and much more.

Tripathy has retired after 18 years as the 

. The staff of CURE is incredibly grateful for the insight, guidance and inspiration offered by Tripathy, formerly a professor and chairman of the Department of Breast Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

Sabari is an Assistant Professor in the Department of Medicine at NYU Grossman School of Medicine and Director of High Reliability Organization Initiatives at NYU Langone’s Perlmutter Cancer Center.

Watch the full conversation with Tripathy and Sabari on 

 Dr. Tripathy, asking for myself, what advice [do you have] for me moving forward into this role that you so eloquently led for the last 18 years? What do you charge me and with patients, our readership moving forward into hopefully the coming 18 years?

 Well, one thing that I have really enjoyed about my tenure as the editor-in-chief is that I have learned more about other cancers through CURE itself and through my patients. And of course, we do have to study for the board, so I do learn it that way.

 really took the lead when the molecular revolution came around. It was one of the transformers. And boy, did it make a difference. Look at the statistics now in terms of how much better individuals with lung cancer are surviving, and it has really made a big difference.

So, communicating all of this and having patients aware of their options and what lies behind it is so important. So the one piece of advice is, is to make this understandable, be out in front of where the patient needs to be. I think that when a patient reads an issue of CURE magazine — let's say they've been recently diagnosed, or they're moving on to a different line of therapy, I think that what we can provide them can complement what they're hearing from their care team.

It is very involved and very sophisticated material that we are expecting them to know, but I know they're up for the challenge. And if they're able to read an article that coincides with what they have, or if they can even go back to 

 online or in print, I think it will help them ask the right questions and understand a little bit better what they're hearing from the physicians.

So, I think that that is an important thing to keep in mind. Again, this is a patient-driven effort we're living with and we're contributing to. And I think that those really are our guiding principles. I look at CURE magazine sort of as the third rail, and to really help provide that information and perspective that is unique, that uniquely can come from this particular venue, and the way we state it and communicate it.

Transcript has been edited for clarity and conciseness.

Videos

 Discussing the Mission of CURE With Our Former and New Editors-In-Chief

Early detection, personalized treatment and strong support systems are key to improving outcomes for multiple myeloma patients, Dr. Joseph Mikhael explains.

Early detection of multiple myeloma, marked by fatigue, bone pain, and anemia, coupled with modern, patient-centered treatments like targeted therapies and supportive care, significantly improves outcomes and quality of life, an expert said.

CURE spoke with Dr. Joseph Mikhael, a professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute, an affiliate of City of Hope Cancer Center, and Chief Medical Officer of the International Myeloma Foundation. In the interview, he spoke about the importance of recognizing the symptoms of myeloma, making informed treatment decisions and the role of supportive care in managing the disease.

CURE: What are some early warning signs of multiple myeloma that patients should be aware of, and when should they seek medical evaluation?

: Typically, the signs and symptoms that patients have are that they experience fatigue, and not just the regular fatigue you and I might face on a regular basis, but when it really is beyond what is normal, an ongoing weakness that is not typical.

No. 2 is bone pain, or pain in the distribution of our bones. This is often in our backs, where we have obviously a lot of bones, because myeloma attacks the bone. And so often our patients — over half of our patients — present with bone pain.

And the third most common reason is what we call anemia, or a low hemoglobin. If that blood test has been done, a lot of times, family doctors and primary care will measure hemoglobin level in terms of what we call a CBC, or complete blood count. And about three quarters of the time, our patients have a low hemoglobin.

Now, of course, there's lots of causes for fatigue, there's lots of causes for bone pain, there are lots of causes for anemia. And myeloma is not the one that comes to the top of mind with these very common things. But when those are going on, and there really isn't a clear explanation, we want people to start to think about the potential of multiple myeloma. This is particularly important in patients who are at higher risk. Myeloma is more common as we get older, in particular, as patients get into their 60s and 70s, those of us of African descent are at twice the risk, and individuals of Latino American background also are diagnosed at a younger age.

What are the current standard treatments for myeloma? And how can patients work with their care teams to make informed treatment decisions?

Myeloma has gone through a revolution over the last several years. When I started in myeloma, over 20 years ago, we maybe had one or two drugs to treat it. Now we have 20 drugs to treat myeloma in a very different approach. I would start by the concept of saying, … “I don't treat myeloma. I treat people.” And so, it's important that patients realize and their care partners that they are the center of the attention; not the doctor or the provider, but the patient is at the center. And with all of these options that we have, the concept of shared decision making is so important, that patients feel a part of that decision making process.

What should patients know about these treatment options, whether that be immunotherapy or targeted therapy, and how might these new approaches impact their prognosis?

These are exciting times in cancer therapy, in general and in particular in multiple myeloma, where historically, we had to use the sorts of treatments that were really tough on the patient, not just tough on their myeloma. But now we have come to an era where we can be much more targeted. That is to say, we can try and hit the myeloma cell, but not the rest of the patient, as it were. And these are through novel treatments, things like monoclonal antibodies and antibody drug conjugates, different approaches where we can actually hone in on the specific myeloma cell, target it for destruction and not the cells around it. And this is clearly improving not only the quantity of patients’ lives, but the quality of patients’ lives.

Furthermore, the next huge wave is what we often call immunotherapy, which is basically the concept of employing a patient's own immune system — because it's there, it's trained to fight. It's the patient's own immune system, so they're not going to reject it, as it were, but engaging their own immune system to take down their own multiple myeloma. We do this now in myeloma, two primary ways. First is called CAR-T cell therapy, or chimeric antigen receptor T-cell therapy. I know it's a lot of words, but the key word there is receptor.

And so what we do is we take T cells out of a patient. T cells are just some of the cells that live in our body. They're kind of like soldier cells. They've been trained to fight. We take them out of the patient, and we essentially train them to fight against their myeloma. We put a receptor on the outside of them that is specific to that patient's myeloma, multiply them and give them back to the patient. So now these amped up soldier cells are just aching to find myeloma. They go find myeloma and they destroy it. I mean, this almost sounds like a futuristic movie, but it is actually what we're doing right now. And we have seen unprecedented response rates with CAR-T cell therapy, and it gives people a period of time off treatment.

What supportive care strategies can help improve daily life for patients living with myeloma.

No. 1, open, honest, clear communication with your healthcare team. Sharing the side effects that you're experiencing, what you're going through, both emotionally and physiologically, as it were, that becomes so important, because we want to 

 through this. We can pick up side effects early on and make adjustments, or provide other supportive care medications that may overcome that. And that approach is so important. We have actually learned in oncology, when you have a strong relationship with your healthcare team, it actually improves your survival.

No. 2, make sure you have your own support. That support can be from your family, from your friends and, indeed, from support groups. The 

 has over 150 support groups across the country. And we've also demonstrated that when patients have support around them, they actually have better outcomes because they're better informed and they're better empowered to face the future.

And No. 3, I always talk about empowerment through education. Not everybody wants to learn every last detail about every aspect of their disease, but knowledge is power.

Transcript was edited for clarity and conciseness.

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

subscribe to CURE®’s newsletters here.

Early detection of multiple myeloma, characterized by symptoms such as fatigue, bone pain, and anemia, is crucial for improving patient outcomes. Modern treatments, including targeted therapies and immunotherapy, have revolutionized management, enhancing both survival and quality of life. Patient-centered care, emphasizing shared decision-making, is vital. Supportive care strategies, such as open communication with healthcare teams and strong personal support networks, further improve patient experiences and outcomes. Education empowers patients, enabling them to make informed decisions about their treatment and manage their condition effectively.

Dr. Joseph Mikhael discusses early signs, treatments and supportive care for multiple myeloma in an interview with CURE. 

Expert Explains Early Signs, Treatment Advances and Care in Multiple Myeloma

FDA approves Stoboclo and Osenvelt biosimilars for bone health during cancer treatment.

The Food and Drug Administration (FDA) has approved Stoboclo (CT-P41, denosumab-bmwo) and Osenvelt (CT-P41, denosumab-bmwo), biosimilars referencing Prolia (denosumab) and Xgeva (denosumab), to protect bone health in patients undergoing cancer treatment.

The approval was announced in a news release from biopharmaceutical company Celltrion. According to the news release, Stoboclo and Osenvelt are expected to be available in the United States in June 2025.

Biosimilar drugs, according to the National Cancer Institute, are very much like another biological drug, referred to as the reference drug, that has already been approved by the FDA. Additionally, these drugs must be shown to be as safe as, work as well as and work in a similar way as the reference drug.

Among patients with cancer, Xgeva is approved to treat giant cell tumors of the bone that cannot be removed by surgery and hypercalcemia of malignancy that got worse after treatment with bisphosphonates, according to the National Cancer Institute. It is also approved to prevent broken bones or other bone problems caused by multiple myeloma, or by solid tumors that have spread to the bone, according to the National Cancer Institute.

 to increase bone mass among adults with a high risk of breaking bones and is used among patients with breast cancer receiving aromatase inhibitor therapy and patients with prostate cancer receiving androgen deprivation therapy, the National Cancer Institute noted.

The drug is also being studied in the treatment of other conditions and types of cancer, according to the National Cancer Institute.

Hypercalcemia: High levels of calcium in the blood.

Bisphosphonates: Medications used to treat bone conditions.

Aromatase inhibitor therapy: Treatments that lower estrogen levels in the body.

Androgen deprivation therapy: Treatment to lower the level of androgens in the body.

Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions.

Pharmacokinetics: The activity of drugs in the body over a period of time.

Immunogenicity: The ability of a substance that contains antigens to cause the body to make an immune response against that substance.

“[Prolia and Xgeva are] used to improve or protect 

 in patients with osteoporosis or those undergoing various cancer treatments and as a therapy for a lifetime for postmenopausal [patients with osteoporosis],” said Jean-Yves Reginster, Professor of Medicine, Protein Research Chair, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia and Director WHO Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging, Liège, Belgium. "Biosimilars have expanded into new therapeutic areas such as immunology, oncology and ophthalmology, as they continue to offer significant cost-saving potential while expanding patient access. Having a [Prolia and Xgeva] product with a clinically proven track record in quality and safety is a valuable addition for my patients."

The approval, according to the news release, is based on data including results of phase 3 clinical trials among postmenopausal women with osteoporosis intended to evaluate the effectiveness, pharmacodynamics, pharmacokinetics, safety and immunogenicity of Stoboclo and Osenvelt in reference to Prolia and Xgeva, with study results demonstrating that the former had equivalent effectiveness and pharmacodynamics to the latter, with similar pharmacokinetics and comparable safety and immunogenicity.

"The approval of Stoboclo and Osenvelt is another step forward in our efforts to deliver cost-effective and high-quality treatments that address critical unmet needs in osteoporosis-related fracture as well as cancer-related skeletal events," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, in the news release. "Patients deserve therapeutic options that have the potential to make real impacts on their care and their lives."

The FDA has approved Stoboclo and Osenvelt, biosimilars of Prolia and Xgeva, for bone health in cancer patients. These biosimilars, expected in the U.S. by June 2025, offer similar safety and efficacy as their reference drugs. Xgeva treats bone-related issues in cancer patients, while Prolia increases bone mass in high-risk adults. The approval is based on phase 3 trials showing equivalent effectiveness and safety. Biosimilars like these expand therapeutic options, offering cost savings and increased access in oncology and other fields.

The FDA has approved Stoboclo and Osenvelt to address skeletal issues faced by patients with cancer.

Darlene Dobkowski, MA

Empowering the Immune System

Discussing the Mission of CURE With Our Former and New Editors-In-Chief

Expert Explains Early Signs, Treatment Advances and Care in Multiple Myeloma

FDA Approves Biosimilars for Cancer-Related Skeletal Events

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