Why the Toughest Metastatic Melanoma Cases Come to this Philadelphia Hospital—and the Breakthrough Therapy Giving Them a Fighting Chance

Dr. Farma meets with a patient to discuss treatment options.

While the rates of metastatic melanoma are on the rise—particularly in younger people—TIL (tumor-infiltrating lymphocyte) therapy at Fox Chase Cancer Center is a high-risk, high-reward therapy for those who may be running out of therapeutic options.

Fox Chase has developed one of the most comprehensive multidisciplinary melanoma programs in the region and began offering TIL therapy for those with metastatic disease with or without a BRAF mutation who have not responded to prior treatment modalities.

TIL is an FDA-approved, cutting-edge treatment for metastatic melanoma patients who are not responding to their first line treatment. It is a one-time treatment specifically bio-engineered for each patient, essentially turning the patient’s own T-cells (or lymphocytes) into cancer-fighting missiles.

This complicated treatment requires critical timing and a highly specialized multidisciplinary team to deliver it. Fox Chase, one of the first cancer centers in the country, has decades of experience in cellular therapies, including stem-cell transplantation, and more than a decade of leadership in clinical trials of adoptive T-cell and other immune effector therapies – some of which helped paved the way for today’s approved treatments. The institution has developed a robust multidisciplinary clinical and administrative structure to handle these complex therapies.

“Treating patients with all kinds of cancer is really a team sport,” says Jeffrey M. Farma, MD, FACS, Chair and Professor, Department of Surgery at Fox Chase Cancer Center.

Here, the surgical oncology, medical oncology and cellular treatment departments work cohesively to best serve patients and even have outpatient clinics next to one another. “We’re constantly talking in real time and devising plans,” Dr. Farma says.

TIL requires critical timing and a highly specialized multidisciplinary team to deliver it.

“With such a large infrastructure and a multidisciplinary approach, it’s very easy for us to communicate effectively,” says Anthony J. Olszanski, MD, RPh, Professor and Vice Chair of Clinical Research, Department of Hematology/Oncology; Chief, Section of Solid Tumor Oncology; and Co-Director, Melanoma and Skin Cancer Program. “We’re following the patient globally as they’re on this path towards their next therapy. I think that’s what’s really unique. So many centers, if they have a handoff, they literally hand off and forget. We’re not forgetting.”

Each week, patients are reviewed at a multidisciplinary tumor board. The team brings together physicians from across cancer care — medical, surgical, and radiation oncologists, dermatologists, dermatopathologists, and nuclear medicine doctors — as well as genetic counselors, nurses, and social workers. By combining their expertise, they develop a unified treatment plan for each patient.

“It’s that team approach that we do very, very well and I would argue we do it better than most anywhere in the region,” Dr. Farma says. “It’s due to our nimbleness, it’s due to our size, it’s due to our history. We have an exceedingly robust melanoma team, and we’re really excited to offer this novel therapy in our region allowing us to treat patients that are running out of treatment options.”

Dr. Farma prepares for surgery.

The Road to TIL

Who qualifies for TIL? Someone with advanced or metastatic melanoma who have stable disease on immunotherapy or are experiencing slow disease progression, may be considered ideal candidates for TIL therapy.

“It’s an aggressive therapy,” says Dr. Farma. “The patient has to be someone who is robust and can tolerate it.”

It takes about six weeks to go through pre-testing, insurance approval, eligibility determination and scheduling surgery, then another three weeks for the manufacturer to create the bioengineered cells for immunotherapy. Due to the long lead time, Fox Chase recommends that patients come in during their first-line treatment so that they are ready to go, before realizing their current treatment may not be effective. It also prevents the patient from becoming sicker while the preparatory process is underway.

“Seeing these patients early is really key,” says Dr. Olszanski. Even if they may not need TIL therapy, it’s better to come in earlier for information. The team says they are happy to talk to patients and determine if they are eligible and put the treatment on their radar.

“Knowing it’s an option earlier is so much better for everyone because we can plan,” Dr. Farma says. “When we’re trying to rush things and it’s a race against time, it often doesn’t work out.”

Dr. Olszanski is a renowned melanoma specialist.

How the Treatment Works

The approval process and the treatment require three different units–cellular therapy, medical oncology and surgical oncology working together to manage the process.

“My job is to make sure the patient is suitable in terms of safety and eligibility of the proposed treatment,” says Rashmi Khanal, MD, Associate Professor, Department of Bone Marrow Transplant and Cellular Therapies at Fox Chase Cancer Center, who institutes the cellular therapy. The treatment is aggressive, so Dr. Khanal ensures the patient can tolerate it, which usually means no underlying cardiac or lung disease, preserved kidney and liver function, as well as good performance status.

Younger patients are often the ones who qualify, but “I’ll never use age as a cut off for anyone,” Dr. Farma says.

The patients are evaluated within the cancer center by various disciplines, and then it is presented to an internal committee for final approval.

“The identification, the preparation of the patient, the surgery and then the transfer to treatment when it’s time for cellular therapy is really seamless,” Dr. Olszanski says.

When a qualified patient is identified, surgery is scheduled. This may be as small as removing a lymph node or as complex as a liver or lung operation. The surgical oncologist performs the procedure to obtain the tissue needed to prepare the patient’s cells for treatment.

“TILs are like melanoma-seeking white cells,” says Dr. Farma. “We remove the tumor tissue and expand those cells over six weeks until they number in the billions.”

The tumor is then sent to the manufacturer to make the re-engineered cells, which Dr. Khanal administers.

Immunotherapy is extremely intensive, taking up to 20 days in the hospital and including chemotherapy and other treatments in addition to the TIL cells.

“Because this therapy places temporary but intense demands on the body, patients are cared for in bone marrow transplant rooms with positive-pressure HEPA filters to guard against infection, by a team of doctors and nurses experienced in supporting people with severely weakened immune systems — expertise not typically available outside transplant centers, says Dr. Olszanski.”

The patients are monitored closely throughout the treatment.

The patient is followed by the Cellular Therapy team of Dr. Khanal and colleagues for the first 30 to 60 days while they track the patient’s blood and immune system before transferring them back to medical oncology. Within two months after treatment, restaging scans are performed to determine the response to therapy, then repeat imaging is performed every two months.

The follow-up care with referring physicians is coordinated and ongoing.

“I think it’s really important for providers out there to know that this is an option,” Dr. Farma says. “It’s thrilling to know that this is out there and that a lot of patients can be eligible for this.”

Dr. Khanal answers a patient’s questions.

Results of TIL Immunotherapy

Ten to 15 years ago, there were limited options for patients with metastatic melanoma. “Why I love what we do is that is that we’re advancing discoveries and changing how we treat patients,” says Dr. Farma.

In the TIL clinical trial, there was a 32% objective response rate, meaning the tumors shrank.

“With time, these numbers usually get better because we’re treating more patients,” Dr. Farma says. In 6% of the clinical trial patients, the tumors went away completely. “Now there are patients that we can cure with metastatic melanoma, which is just mind-blowing. That’s changing lives, changing families.”

In the remaining patients who have a partial response, the tumors may shrink enough to open up further surgical options, or it keeps the disease at bay to improve quality of life and prolong survival, Dr. Farma says. New FDA treatments for melanoma are approved frequently, so this treatment can buy more time until another treatment becomes available.

“These patients become really well known to us, and we care for them,” Dr. Olszanski says. “We offer deeply personalized care that you’re just not going to get at most other academic medical centers.”