Thirty Years in the Making: The Groundbreaking Approval of Lifileucel for Metastatic Melanoma With Matthew Hadfield, DO, and Richard Carvajal, MD

Following the recent approval of lifileucel for unresectable or metastatic melanoma—the first cellular therapy to receive an approval for solid tumors—Matthew Hadfield, DO, member of the Oncology Data Advisor Fellows Forum and third-year Fellow at Brown University, sat down with Richard Carvajal, MD, Oncology Data Advisor Editorial Board Member and the Deputy Physician-in-Chief at the Northwell Health Cancer Institute, to discuss the significance of this approval, what it means for the treatment landscape of melanoma, and what to look forward to for the future of treating melanoma.

Matthew Hadfield, DO: I’m Matt Hadfield. I’m a third-year Medical Oncology Fellow at Brown University in Legorreta Cancer Center in Providence, Rhode Island, with an interest in melanoma and early-phase clinical trials. I’m going to be staying on as a faculty member here in a few months specializing in that. And I’m very happy to be talking today with Dr. Carvajal—if you want to introduce yourself?

Richard Carvajal, MD: My name’s Richard Carvajal, I’m a Medical Oncologist and the Deputy Physician-in-Chief here at the Northwell Health Cancer Institute. I focus on melanomas with a particular interest in rare subtypes of melanomas and I’ve done work in early-phase drug development.

Dr. Hadfield: Great. It’s so nice to be able to carve out some time to talk to you today. I think that the primary focus of our conversation is going to be on the recent FDA approval of tumor-infiltrating lymphocytes, which has been a long time coming. What are your off-hand opinions on this therapy where it’s going to fit into the treatment paradigm for melanoma patients.

Dr. Carvajal: Yeah, this is so huge, this therapy. It’s the first cell therapy to be approved for solid tumors. And I think one, it’s really cool that this is another first for the melanoma field, right?

Dr. Hadfield: Yeah, it leads the way.

Dr. Carvajal: Melanoma leads the way. We’ve done checkpoint inhibition, bispecifics for uveal cell therapy; so, a lot of firsts for melanoma, but it’s also really remarkable how long this therapy has been in development. The history of this is amazing.

Dr. Hadfield: I would love to hear your perspective on that because this was really something that was conceived at the National Institute of Health (NIH), it’s been decades, and now we’re finally able to roll it out to the broader community. I mean, what’s your perspective on that development?

Dr. Carvajal: Kudos to Steve Rosenberg for really believing in this and pushing this forward. What a complicated therapy. He’s been working on this since the 80s!

Dr. Hadfield: Yeah, it’s pretty impressive. I mean, the commitment to not giving up on that as a potential modality to treat patients, it’s pretty remarkable.

Dr. Carvajal: It’s really remarkable. And I think for me, Matt, for you, for all of us, it just shows you how hard this is—30 years!

Dr. Hadfield: Absolutely. I guess for people who may not be familiar with tumor-infiltrating lymphocytes, the process here is you take the tumor out of patients, you harvest the lymphocytes from the tumor, you expand them, and then you give them back to the patient. I think what I’ve seen anecdotally is it’s about a two-to-three–week process. Has that been your experience?

Dr. Carvajal: Yes, the process has been standardized quite nicely here. Historically some of the challenges with this one is patient selection has always been really a big deal, and this is one of the big challenges with the development of this sort of concept. One, you have to have a patient who has harvestable tumor, someone who can undergo the surgery, get a big enough tumor to extract the T cells, and then after that, the patients have to have enough time to wait. They have to be able to live long enough to expand those T cells, which used to take a long time. Now with lifileucel, it’s a 21-day process, and most patients can wait for that. You have the lymphodepletion beforehand and the cells and you have to wait for the recovery. So, it’s definitely still a process—selection is still really important. This is not a therapy that you’re going to be able to give to everyone.

Dr. Hadfield: Right, and this isn’t the type of therapy where if someone’s having rapid disease progression and needs to start something quickly—this is not the therapy we’re going to be turning to, but for those maybe slower-growing, who have some time, and who have the appropriate tissue. And this is a therapy that in the trial it was proven to be pretty effective in post–checkpoint inhibitor patients, which is a population we really struggle to treat.

Dr. Carvajal: Yes. This is the first therapy approved for that indication. What do we do after checkpoint blockade is an effective or after BRAF, if they have a BRAF mutation, this is it. This is all we have, and the outcomes are really good. So, you have response rates where about a third of the patients get radiographic responses. Look at the expanded data set. Over half of those responses are lasting over a year. And we still have to see how many of these are going to translate to that cure that we’re after, but there will be some of them.

Dr. Hadfield: Right. One thing that I’ve been curious about, and I mean, to your point, if you have BRAF-wildtype disease, or if you have progressed on checkpoint inhibitors and targeted therapy, I mean, we really don’t have anything outside of clinical trials. Now we have TIL therapy, but there hasn’t been historically.

Do you think there are going to be any challenges, because one of the things that I’ve thought about with some of these more novel therapies is, can we roll this out to a broader population in the country and not just silo these types of therapies into big academic medical centers? Do you think that’s going to be possible in the future? Or do you think this is going to be the type of therapy where people are really going to have to make it to bigger centers to get treated?

Dr. Carvajal: Oh gosh. I hope the answer is the former, that we’re able to give access more locally, but certainly that’s not going to be in the near term. I remember when, for instance, ipilimumab/nivolumab (ipi/nivo) was first approved, or even just checkpoint blockade. That was something that people were nervous about in the community. So, it took some time before people got comfortable doing that. This is a complicated therapy.

Dr. Hadfield: Yes, it absolutely is. And I think that’s the other thing too—I’m very interested in immunotherapy toxicities—as we start to give more and more of these, even in the uveal melanoma world, things like tebentafusp with cytokine release syndrome (CRS) monitoring and things like that, that toxicities are getting quite complicated: immunotherapies, antibody-drug conjugates, overlapping between the two, certain solid tumors, and then we have these novel therapies. I could see that as being a challenge too, if you roll this out to more community centers, because there’s a lot of toxicity to manage too. That’s pretty nuanced and pretty complicated.

Dr. Carvajal: I think in the near term, the answer is that it is just going to be select centers. People will travel for this; people will self-select who is going to get this therapy as cell therapy becomes more prevalent. We’ve got six chimeric antigen receptor (CAR) Ts approved for hematologic malignancies and more in development, so this will become more widespread. That’s going to take a period of time.

Dr. Hadfield: Absolutely. The paradigm in melanoma and solid tumors has been to push towards combinations. So, we came up with ipilimumab, then we combine them with nivolumab and LAG-3 treatments with nivolumab. Again, another, the most recent checkpoint inhibitor melanoma led the way again there. So, in the future therapeutic combinations with pills, do you think it’ll make sense to combine with a checkpoint inhibitor or some other therapy? Or do you think it really will be something that sort of stands on its own?

Dr. Carvajal: I like the idea of the combinations. And so, in fact, Iovance is going for a first-line indication. So, there are trials now of programmed cell death protein 1 (PD-1) plus tumor-infiltrating lymphocytes (TILs) in the frontline setting where in the data that’s been generated so far, the responses seem to be a little bit better with the combination. They in fact may be better. So, I think we will see that combination makes a lot of sense, and we’ll know the answer in a few years.

Dr. Hadfield: Yes, it’s exciting. I mean, this is a remarkable time as someone who’s just finishing up my training now. Now it’s an unbelievable time to be training given just how rapid and how many therapeutic options that continue to be developed every year, and this is one of them. I mean, this is a monumental thing for solid tumor oncology to have the first cellular therapy approved. And as you said earlier, as two people who think a lot about melanoma, it’s very exciting to be a part of that community as well and lead the way.

This has been a great conversation. Thank you so much for joining, and I hope our listeners were able to learn something from this.

Dr. Carvajal: Thanks a lot, Matt. Thanks for having me.

Dr. Hadfield: Alright, take care.

About Dr. Hadfield and Dr. Carvajal

Matthew Hadfield, DO, is a Hematology/Oncology Fellow at Brown University/Legorreta Cancer Center in Providence, Rhode Island. Prior to fellowship, he completed his Internal Medicine Residency at the University of Connecticut in 2021. Dr. Hadfield’s research focuses on melanoma and early-phase clinical trials. To date, he has published numerous peer-reviewed articles and studies, and he has presented his research at multiple national and international meetings. His main areas of interest include early-phase drug development, novel immunotherapeutic combinations to overcome therapeutic resistance, and predictive biomarkers for immunotherapy toxicities.

Richard D. Carvajal, MD, is Deputy Physician-in-Chief and Director of Medical Oncology at Northwell Health Cancer Institute in New York, where he is also the R.J. Zuckerberg Chair in Medical Oncology. Dr. Carvajal’s research is focused on the development of novel therapies for patients with melanoma and other cancers, including uncommon clinical and molecular subsets such as those arising from the eye (uveal melanomas), mucosal surfaces of the body (mucosal melanomas), and palms of the hands, soles of the feet, or under the fingernails (acral melanomas). He has been the principal or co-investigator of over 500 clinical trials and has authored or coauthored over 200 peer-reviewed manuscripts, books, and book chapters. In addition, Dr. Carvajal serves as Co-Chair of the International Rare Cancer Initiative Uveal Melanoma working group, a joint initiative between the National Cancer Institute, the European Organization for Research and Treatment of Cancer, and the Cancer Research UK to enhance international collaboration in clinical trials for uveal melanoma.


Oncology Data Advisor (2024). Lifileucel granted accelerated approval for unresectable or metastatic melanoma. Available at:

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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