{"id":46542,"date":"2024-03-05T12:00:00","date_gmt":"2024-03-05T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2024\/fda-amtagvi-til-therapy-melanoma"},"modified":"2024-11-03T15:11:52","modified_gmt":"2024-11-03T15:11:52","slug":"first-cancer-til-therapy-gets-fda-approval-for-advanced-melanoma","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/first-cancer-til-therapy-gets-fda-approval-for-advanced-melanoma\/","title":{"rendered":"First Cancer TIL Therapy Gets FDA Approval for Advanced Melanoma"},"content":{"rendered":"

\n
\n
<\/div>
\n
\n

FDA has approved the first treatment for cancer that uses tumor-infiltrating lymphocytes, or TILs.<\/p>\n

Credit: National Cancer Institute<\/p>\n<\/p><\/div>\n<\/figcaption><\/figure>\n<\/p><\/div>\n

In an event more than three decades in the making, the Food and Drug Administration (FDA) has approved lifileucel (Amtagvi), the first treatment for cancer that uses immune cells called tumor-infiltrating lymphocytes, or TILs. Announced on February 16, the agency\u2019s decision also makes lifileucel the first cellular therapy to be approved for a solid tumor<\/a>, the skin cancer melanoma.<\/p>\n

The agency\u2019s accelerated approval<\/a> covers the use of lifileucel for people with advanced melanoma that has gotten worse after treatment with certain immunotherapy<\/a> drugs or targeted therapies.<\/p>\n

As is the case with CAR T-cell therapy<\/a>, another type of cellular therapy, lifileucel is made using a patient\u2019s own T cells<\/a>. And with both therapies, the cells are collected at the hospital where the patient is being treated but are sent away to be manufactured into the final treatment. <\/p>\n

But there\u2019s a key difference between TILs and CAR T-cell therapies.<\/p>\n

For the approved CAR T-cell therapies, the T cells are collected from a patient\u2019s circulating blood. For TIL therapy, by contrast, the T cells are collected from the patient\u2019s tumor. <\/p>\n

Lifileucel\u2019s approval was based on findings from a clinical trial<\/a> sponsored by Iovance Biotherapeutics. Among more than 70 participants who were treated with the lifileucel dose ultimately approved by FDA, nearly one-third had at least some reduction in the size of their tumors (a tumor response), with tumors disappearing completely (a complete response<\/a>) in several participants.<\/p>\n

Moreover, about 40% of those whose cancer responded to lifileucel still had no progression of their cancer a year after receiving the one-time infusion treatment. <\/p>\n

TIL therapy was pioneered by Steven Rosenberg, M.D., and his colleagues in NCI\u2019s Surgery Branch<\/a>. In the late 1980s, Dr. Rosenberg led the first-ever clinical trials of TIL therapy, showing that it could shrink tumors in people with very advanced melanoma. (Dr. Rosenberg was recently given the nation\u2019s highest award for technology and innovation for his work on immunotherapy<\/a>, including the development of TIL therapy.)<\/p>\n

Over the ensuing years, the NCI researchers further refined the process for manufacturing and delivering TIL therapy. In 2011, NCI entered into a cooperative research agreement<\/a> with Iovance to further develop this particular TIL therapy, including conducting larger clinical trials and developing a manufacturing infrastructure, paving the way for FDA approval.<\/p>\n

It\u2019s been a long time coming, Dr. Rosenberg acknowledged. The new approval \u201cis a big step,\u201d he said, one which demonstrates that \u201ccellular therapy is joining the mainstream of cancer treatment.\u201d<\/p>\n

TILs that just need a little help<\/h2>\n

Six different CAR T-cell therapies have been approved by FDA, all of which are used to treat blood cancers like leukemia and lymphoma.<\/p>\n

With CAR T-cell therapy, the collected immune cells undergo genetic engineering in the laboratory to give them the ability to recognize cancer cells and enhance their ability to kill them. Next, they are grown, or expanded, into the hundreds of millions, and then infused into the patient.<\/p>\n

\n
\n
\n

Tumor-infiltrating lymphocytes, or TILs, are T cells collected from a patient’s own tumor. Once isolated from the tumor sample, the TILs are expanded into the billions and infused back into the patient.<\/p>\n

Credit: National Cancer Institute<\/p>\n<\/p><\/div>\n<\/figcaption><\/figure>\n<\/div>\n

With lifileucel, the collected T cells are not engineered before being expanded. That\u2019s because, having been collected from samples of tumor tissue, they\u2019ve already proven that they can recognize and navigate to tumors, Dr. Rosenberg explained. That recognition relies on the presence of specific abnormal proteins<\/a>, or antigens<\/a>, on the surface of the tumor cells.<\/p>\n

But, like a robber who sneaks into a bank but doesn\u2019t have the tools to open the safe, the collected TILs lack the ability or support required to complete the job. What the TILs need are reinforcements\u2014a lot of them\u2014and some encouragement.<\/p>\n

So, although the TILs collected from a patient\u2019s tumor are not genetically changed, there are steps taken during the manufacturing process\u2014including mixing them with a drug called IL-2<\/a>\u2014to help them expand into billions of cancer-fighting immune cells.<\/p>\n

In addition, as part of lifileucel treatment, two measures are taken to enhance the infused TILs ability to attack the cancer and their overall potency. First, in the days prior to receiving lifileucel, patients undergo a few rounds of high-dose \u201clymphodepleting\u201d chemotherapy. And, second, shortly after the lifileucel infusion, they are given several doses of IL-2.<\/p>\n

Long-lasting tumor responses to lifileucel<\/h2>\n

FDA\u2019s approval was based on data from a group of 73 patients in the trial whose cancer had gotten worse despite treatment with a PD-1<\/a>\/PD-L1<\/a>-targeted immune checkpoint inhibitor<\/a> or a BRAF inhibitor and whose lifileucel dose was at least 7.5 billion cells (the dose specified in the approval).<\/p>\n

Longer-term findings from a larger group of 153 patients in the trial were reported in December 2023 at the European Society of Medical Oncology\u2019s (ESMO) 2023 Immuno-Oncology Congress, and they largely mirror the findings from these 73 patients.<\/p>\n

Of the 48 people (31.5%) whose cancer responded to treatment with lifileucel, more than half have lived at least a year without any evidence of their cancer getting worse<\/a>. About 10% of these responses are ongoing\u2014that is, there continues to be no evidence that their cancer is getting worse\u2014and nearly all have lasted several years.<\/p>\n

The longest lasting response is nearly 5 years, one of the trial\u2019s lead researchers, Martin Wermke, M.D., Ph.D., of the University of Dresden in Germany, reported at the ESMO meeting.<\/p>\n

The researchers plan to follow all patients for 5 years from the time of their lifileucel infusion, Dr. Wermke said. Based on the results thus far, he continued, the researchers anticipate that cancer will not get worse or come back in any participants with ongoing responses.<\/p>\n

Who will respond to lifileucel? What about side effects?<\/h2>\n

There are some hints from the results in the larger patient group that might help identify who is most likely to respond to lifileucel, Dr. Wermke explained.<\/p>\n

For example, few people whose cancer had spread to the brain or liver, which was the case for about half of the 153 patients, responded. Responses were also unlikely in people who had larger tumor burdens\u2014that is, a substantial amount of cancer in their body.<\/p>\n

These findings, he noted, suggest that lifileucel might be most effective if it\u2019s given before the cancer has spread to many other parts of the body or individual tumors have become quite large.<\/p>\n

All participants in the trial had side effects caused by the treatment, Dr. Wermke reported. Most, however, were not dangerous and were largely caused by the chemotherapy given before the lifileucel infusion and IL-2 given afterward. The most common included anemia<\/a>, high fevers, and substantial drops in levels of platelets<\/a> and certain white blood cells<\/a>. <\/p>\n

TIL therapy does not appear to cause the often serious immune-related side effects commonly seen in people treated with CAR T-cell therapy, including cytokine release syndrome<\/a> and neurologic effects, Dr. Wermke said.<\/p>\n

He also stressed that the side effects seen in the trial had a consistent and familiar pattern.<\/p>\n

\u201cThey\u2019re all occurring during the first 2 or 3 weeks\u201d after someone receives the treatment, he said. 
\u201cThere are hardly any new [side effects] occurring in the long term,\u201d he said.<\/p>\n

From clinical trials to using TILs in everyday cancer care<\/h2>\n

Iovance announced that it has approved more than 30 treatment centers across the United States to collect tumor samples for making lifileucel and administering the final treatment to patients. There are expected to be 50 such centers by the end of May. <\/p>\n

Initially, all treatments will be manufactured at an Iovance facility or a contracting facility, both in Philadelphia.<\/p>\n

According to the company, a single treatment with lifileucel will cost $515,000. During a company webcast held after the approval, Iovance officials said they expect that many insurance companies will cover the treatment at the same levels as they have for CAR T-cell therapies, which also cost hundreds of thousands of dollars. The company has also established a financial assistance program for patients.<\/p>\n

William Sharfman, M.D., a co-director of the melanoma program at the Johns Hopkins Sidney Kimmel Cancer Center, said the approval is \u201cvery exciting\u201d news for people with advanced melanoma.<\/p>\n

But, Dr. Sharfman cautioned, \u201cthere are several limiting factors\u201d for using lifileucel in patients.<\/p>\n

Among them, he said, is that patients need to be relatively healthy to receive it, which isn\u2019t always the case for people with advanced cancer who have undergone other treatments. <\/p>\n

\u201cPatients really need to have normal heart and lung function,\u201d he said.<\/p>\n

Alexander Shoushtari, M.D., of Memorial Sloan Kettering Cancer Center, who studies cellular therapies, agreed that practical considerations may limit lifileucel\u2019s use. <\/p>\n

\u201cThe relatively high doses of \u2026 chemotherapy given before treatment and the high dose Interleukin-2 after [lifileucel] infusion currently limit the types of people who can undergo it,\u201d Dr. Shoushtari said. <\/p>\n

After lifileucel approval, what comes next?<\/h2>\n

FDA\u2019s approval for melanoma is only the first step for lifileucel. Iovance has already started enrolling participants in a large trial combining lifileucel with the immunotherapy drug pembrolizumab (Keytruda)<\/a> as an initial treatment for advanced melanoma.<\/p>\n

Lifileucel is also well along in testing as a treatment for other cancers, including showing promising tumor responses in people with advanced lung cancer<\/a>, as well as ovarian and head and neck cancers.<\/p>\n

Dr. Rosenberg\u2019s lab and others are testing newer forms of TIL-based therapies in clinical trials, and not just for melanoma, but for other solid cancers.<\/p>\n

\u201cThere are clear examples where TIL therapy has caused regression of [other solid] tumors,\u201d Dr. Rosenberg said. That includes complete eradication of tumors in individual patients with advanced colon cancer<\/a> and advanced breast cancer<\/a> treated in clinical trials at the NIH Clinical Center. <\/p>\n

With this \u201clandmark approval\u201d in hand, there is a lot of optimism surrounding TIL therapy and cellular therapy more broadly, Dr. Shoushtari said. \u201cI expect that this [approval] will be the tip of the iceberg for cellular-based immune therapy for solid tumors,\u201d he added. <\/p>\n

The first-generation TILs like lifileucel are \u201can important advance and proof of concept\u201d that these treatments can be highly effective, he said. \u201cBut much remains to be done to broaden [their] use, both for other cancer types and to a broader range of people with melanoma.\u201d<\/p>\n

Dr. Sharfman agreed. \u201cThat is the challenge: to design better TILs.\u201d<\/p>\n

Researchers are already taking up this challenge, include finding ways to make TILs that are more potent and that can be used in a broader range of solid tumors. Dr. Rosenberg\u2019s group at NCI, for example, has developed a process for identifying TILs that strongly recognize a tumor<\/a> and are most likely to attack it.<\/p>\n

Researchers have also begun genetic engineering of TILs, with the goal of increasing the number of people who respond to the treatment or eliminating the need for the pre-infusion chemotherapy or post-infusion IL-2. <\/p>\n

Dr. Rosenberg stressed that the decades of research on cancer cellular therapies by his and other groups has paved the way for rapid advances.<\/p>\n

\u201cWe now have the knowledge of how to help the immune system target tumors,\u201d particularly the solid tumors \u201cthat are responsible for the vast majority of cancer deaths,\u201d he said. \u201cThere is a world of opportunities out there.\u201d<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

March 5, 2024, by Carmen Phillips FDA has approved the first treatment for cancer that uses tumor-infiltrating lymphocytes, or TILs. Credit: National Cancer Institute In an event more than three decades in the making, the Food and Drug Administration (FDA) has approved lifileucel (Amtagvi), the first treatment for cancer that uses immune cells called tumor-infiltrating […]<\/p>\n","protected":false},"author":2,"featured_media":46543,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-46542","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46542","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=46542"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46542\/revisions"}],"predecessor-version":[{"id":47102,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46542\/revisions\/47102"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/46543"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=46542"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=46542"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=46542"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}