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Topic

Andre H. Goy, MD; Marco L. Davila, MD, PhD; Ajay K. Nooka, MD, MPH, FACP

Community Practice Connections™: Pre-Conference Workshop on Immune Cell-Based Therapy

Go To PER in Chicago

Karen M. Winkfield, MD, PhD; Narjust Florez, MD, FASCO; Gilberto de Lima Lopes Junior, MD, MBA, FASCO; Coral Olazagasti, MD; Vonetta M. Williams, MD, PhD

 Fighting Disparities and Saving Lives: An Exploration of Challenges and Solutions in Cancer Care

Corey Cutler, MD, MPH, FRCP(C); Carrie L. Kitko, MD

BURST Expert Illustrations and Commentaries™: Exploring the Mechanistic Rationale for CSF-1R– Directed Treatment in Chronic GVHD

Asim V. Farooq, MD; Joann Kang, MD; Nita Lee, MD, MPH

(CME) Optimizing Management of Ocular Toxicity in Cancer Patients: The Role of Ophthalmologists in the Spectrum of Care

(COPE) Optimizing Management of Ocular Toxicity in Cancer Patients: The Role of Ophthalmologists in the Spectrum of Care

Andre H. Goy, MD; Monique Hartley-Brown, MD, MMSc (Guest Co-Chair); Chiara Battelli, MD, PhD; Marios Giannakis, MD, PhD; Shail Maingi, MD; Aparna Parikh, MD

Community Practice Connections™: 6th Annual Precision Medicine Symposium – An Illustrated Tumor Board

Jennifer R. Brown, MD, PhD; Alexey V. Danilov, MD, PhD; Matthew S. Davids, MD, MMSc

Medical Crossfire®: Expert Interpretations of the Latest Data in CLL Management – Understanding the Impact of Optimal Treatment Selection on Patient Outcomes

™ Oncology specialty topic page highlights the latest clinical care news related to the development of cell therapies, gene therapies, and engineered and regenerative medicines for various cancers. It also houses video interviews with key opinion leaders in the field of oncology speaking to the related FDA actions, clinical guideline updates, and clinical trial findings in the field of gene and cell therapy for oncologic diseases.

In Episode 3 of ImmunoLogic, Marcela Maus, MD, PhD, discussed her research on CAR-T for treating glioblastoma.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

We're excited to introduce another episode of the 

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Fraietta is joined by cohost 

 a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

the director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center, about her research into the use of chimeric antigen receptor T-cell (CAR-T) therapy to treat glioblastoma. Maus, Fraietta, and Minehart covered topics including challenges and insights from early clinical trials, innovations and clinical results, antigen expression and the possibility of readministration, as well as the autologous versus allogeneic debate.

 is tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. This podcast is an essential resource for those driving the future of immunotherapy.

Interested in co-hosting an episode or being a guest? Have feedback to share? 

If you'd like to get in touch to talk about the show, contact our editorial director, Matt Hoffman: 

Podcasts

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T-Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

In Episode 2 of ImmunoLogic, Bruce Levine, PhD, discussed the current the risk-benefit-ratio for CAR-T therapy.

ImmunoLogic, Episode 2: "Charting New Frontiers in CAR T-Cell Safety" With Bruce Levine, PhD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

 the Barbara and Edward Netter Professor in Cancer Gene Therapy at the Perelman School of Medicine at the University of Pennsylvania, about the black box warnings for secondary malignancies that were issued by the FDA with regard to the autologous chimeric antigen receptor T-cell (CAR-T) therapies approved by the agency, and the implications of the findings that informed these warnings for the risk-benefit ratio of these therapies. Levine, Fraietta, and Minehart covered topics including risk and informed consent, genetic modification as it relates to safety, epitope spreading and T-cell stimulation, and the importance of the National Institutes of Health (NIH) to CAR T-cell research.

In Episode 1 of ImmunoLogic, Stephen J. Schuster, MD, discussed the potential of treating lymphoma without chemotherapy.

ImmunoLogic, Episode 1: "Chemo-Free Lymphoma? Seriously?" With Stephen J. Schuster, MD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

, the director of the Lymphoma Program at Penn Medicine, about the changing role of chemotherapy in lymphoma treatment, and the potential for its elimination. Schuster covered topics including trials for chimeric antigen receptor T-cell (CAR-T) therapy without lymphodepletion, using AI to predict CAR-T treatment outcomes, the importance of T-cell fitness, and the role of persistence in CAR-T success.

Joseph Fraietta, PhD, previews his new podcast, ImmunoLogic

ImmunoLogic Episode 0

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions.

In this short preview episode, Fraietta outlines the podcast’s mission to scrutinize the critical milestones shaping immunotherapy today and discuss how episodes will analyze the journey from bench to bedside—focusing on the real-world implementation of clinical data and the impact of regulatory achievements on patient outcomes. Topics will include discussions on chimeric antigen receptor (CAR) T-cell therapies, tumor-infiltrating lymphocyte (TIL)-based approaches, antibody-driven treatments, and the latest advances in gene editing technologies such as CRISPR, with a goal of expanding the conversation outside of the field of oncology.

 will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. With its first full episode launching in early 2025, this podcast promises to be an essential resource for those driving the future of immunotherapy.

Hosted by Joseph Fraietta, PhD, ImmunoLogic will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility.

CGTLive® Presents: ImmunoLogic, A Video Podcast With Joseph Fraietta, PhD

Review top news and interview highlights from the week ending May 9, 2025.

CGTLive®’s Weekly Rewind – May 9, 2025

In observance of World Ovarian Cancer Day, held annually on May 8, we took a look back at news in cell therapy for ovarian cancer indications.

World Ovarian Cancer Day 2025: Looking Back at Progress for Cell Therapy

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in cell and gene therapies. 

Around the Helix: Cell and Gene Therapy Company Updates – May 7, 2025

Review top news and interview highlights from the week ending May 2, 2025.

CGTLive®’s Weekly Rewind – May 2, 2025

Catch up on any of the key data updates you may have missed last month, with coverage highlights from the CGTLive™ team. 

Data Roundup: April 2025 Features Updates for Cardiomyopathy Gene Therapy, Myasthenia Gravis CAR-T, and More

This is the fourth part of an interview with Renier Brentjens, MD, PhD. For the first part,

The chair of the department of medicine at Roswell Park Comprehensive Cancer Center discussed the need to bring more innovations from nonclinical research to patients.

Renier Brentjens, MD, PhD, on Supporting Translational Cell Therapy Research

“...[W]e kept publishing more ways of curing mice, and it looked better, the doses were lower, and all of this—and of all that technology that was described, much of it remarkably elegant, very little of it has seeped into the realm of translational research, into clinical trials, and for better outcomes. That was actually a significant source of frustration for me, because we were doing all of this, and none of it was actually doing what it was intended to do, which was to translate. Translating cell therapy, unlike drugs that can be manufactured en mass, translating cell therapies is an expensive endeavor.”

The chimeric antigen receptor T-cell (CAR-T) therapy products currently approved by the FDA are based on rather dated technology, with the chimeric receptors themselves having been detailed in papers published in 2002 and 2004. Since then, numerous papers have been published describing new innovations and improvements that showed promise in preclinical research. Unfortunately, however, because of the high costs of translational research in cell therapy, comparatively few of these innovations have made their way to the clinic.

, Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center, shared his thoughts on the importance of supporting translation research in cell therapy. Brentjens pointed out that clinical trial costs are often in the millions and that there is a lack of sufficient grant support from academic institutions. He noted that when he arrived at Roswell Park in Buffalo, he was drawn by the institution's commitment to advancing cell therapy through philanthropy and infrastructure. Roswell now has the largest academic GMP facility for producing CAR T-cells in the United States.

Brentjens emphasized that progress isn’t about more publications, but about improving real patient outcomes, and that Roswell’s model supports practical, cost-effective clinical translation, turning lab research into treatments. He expressed hope that this approach can help bridge the divide between bench science and bedside care.

Videos

This is the third part of an interview with Renier Brentjens, MD, PhD. For the first part,

The chair of the department of medicine at Roswell Park Comprehensive Cancer Center discussed his views on toxicities and costs associated with CAR-T, and when and how the field should address them.

Renier Brentjens, MD, PhD, on Barriers to Accessibility for CAR-T 

“Look, I'm a leukemia doc. I spent years giving high dose chemotherapy to our leukemia patients... So it's not that I'm not empathetic to the toxicities that these cells can cause—I certainly am, and we certainly have developed algorithms to minimize those toxicities—but I think most of what we do as medical oncologists with anychemotherapy is fraught with tons of toxicities, and so we have to accept that, and we have to deal with it. For now, I don't think it's a reason to stop developing this technology.”

Chimeric antigen receptor T-cell (CAR-T) therapy has proved to be an effective tool in the toolbox for addressing hematologic malignancies, having now been incorporated as a standard part of the landscape of care. Furthermore, efforts to bring the modality to solid tumors, with necessary modifications to address the unique challenges of those tumor types, are now underway.

Although, several aspects of CAR-T may limit its accessibility. Two important considerations are the potential toxicity caused by the therapy and the high cost of manufacturing CAR-T products. A myriad of research and development programs intended to mitigate these drawbacks are now underway across an array of companies and institutions.

During a broader discussion on the future of CAR-T therapy, 

 asked Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center, for his thoughts on the barriers to accessibility to CAR-T and how the field is dealing with them. Brentjens emphasized that while adverse reactions associated with CAR-T like cytokine release syndrome are serious, they’re manageable. Furthermore, he pointed out that at the moment, toxicity is essentially a fact of life for the field of oncology, as other standard of care modalities like chemotherapy also have toxicities strongly associated with them. Therefore, toxicity alone should not be a reason to stop developing new CAR-T treatments.

With regard to cost, Brentjens stated that costs for CAR-T are likely to go down over time as the technology develops and more products enter the commercial market. Although, he gave his view that academics engaged in research and development for CAR-T products should focus first on developing products capable of effectively eradicating metastatic tumors before shifting the focus to bringing down costs.

Renier Brentjens, MD, PhD, on Barriers to Accessibility for CAR-T

This is the second part of an interview with Renier Brentjens, MD, PhD. For the first part,

The chair of the department of medicine at Roswell Park Comprehensive Cancer Center discussed his view on how the cell therapy field should proceed with regard to innovation.

Renier Brentjens, MD, PhD, on Autologous Versus Allogeneic CAR-T for the Near-Term Future

“...[T]here's certainly virtue to having off-the-shelf products. It's probably going to be cheaper, it's probably going to be easier, and provide more access to more patients for this technology, but to start working on the seat belts and the air conditioning before you've optimized the engine, to me at least, philosophically doesn't make sense.”

Over the past 5 to 10 years, chimeric antigen receptor T-cell (CAR-T) therapy has established itself as an effective treatment modality for blood cancers, but it has become clear that new innovations are needed to tackle solid tumor indications. Currently, all FDA-approved CAR-T products for hematologic malignancy indications are based on the use of autologous, alpha-beta (αβ) T-cells. One approach is to apply these cells with modifications, such as additional genetic engineering in the form of 

, to the problem of solid tumors. Another approach is to utilize different cell types, such as gamma-delta T-cells or natural killer (NK) cells, as the basis for CAR cell therapy, or to use allogeneic αβ T-cells rather than autologous ones. Some companies and institutions are even combining allogeneic approaches with nontraditional cell types.

In an interview with Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center, on the topic of future innovations in the field of CAR-T, 

 asked Brentjens for his view on the autologous versus allogeneic debate in oncology cell therapy. Brentjens expressed the opinion that although alternative approaches have potential advantages and rationales behind them, the field ought to firmly establish the efficacy of autologous, αβ CAR T-cells in solid tumors before bringing additional variables into the mix. He utilized the analogy of perfecting the engine of an automobile before worrying about modifications to things such as the air condition or stereo in order to make his point.

The chair of the department of medicine at Roswell Park Comprehensive Cancer Center discussed the innovations necessary to make CAR-T therapy effective in solid tumor indications.

Renier Brentjens, MD, PhD, on Using Armored CAR T-Cells to Tackle Solid Tumors

“I think over the brief 20 year span that I've been doing this work, I think we philosophically kind of changed how we look at [CAR T-cells as cytotoxic agents], and we realized that that the CAR T-cell may be more of a spark rather than the actual explosion. It's the spark that sets off a downstream effect where an immune system that is actually quite reasonably sophisticated in recognizing cancer cells can overcome the defenses that cancer cells create around themselves to stop cell therapies from working.”

Over the past 5 to 10 years, chimeric antigen receptor T-cell (CAR-T) therapy has established itself as an effective treatment modality for blood cancers, with several products having been approved by the FDA for such indications. Although, attempts to apply the same approach to solid tumor indications have proven difficult because of key differences in solid tumor biology. As such, it has become clear that a modified approach to CAR-T therapy will be necessary to make the modality able to provide clinically meaningful benefit for solid tumors. One such approach is the concept of “armored CAR T-cells", CAR-T products that have additional genetic modifications intended to combat cancer cells beyond the use of the CAR itself.

 recently spoke with Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center, about how armored CAR T-cells can help bridge the gap necessary to make CAR-T effective in solid tumors. Brentjens pointed out that unlike blood cancers, solid tumors are more complex, often surrounded by nontumor cells that block immune responses. Armored CAR T-cells can reshape this environment and trigger the body’s natural immune system to help attack the cancer. Furthermore, he emphasized that in solid tumors armored CAR T-cells may help address antigen escape, which is typically an even greater challenge for solid tumors than it is in blood cancers.

This video originally appeared on our sister site,

The director of the Autologous Hematopoietic Cell Transplantation, Cell Therapy and Transplant Program at the Hospital of the University of Pennsylvania discussed data from the phase 2 BMT CTN 1902 trial.

Bhagirathbhai R. Dholaria, MD, on Evaluating P-BCMA-ALLO1 in R/R Myeloma

“We set a bar for ourselves to see if we could increase [the proportion of patients who converted to a complete response (CR)] to at least 30%, and what we found actually was that we did even better than that by a good amount. Sixty-three percent of patients converted to CR, and another 24% upgraded their response in some other way. A total of 87% of patients improved their response to some extent.”

Bristol Myers Squibb and 2seventy bio's idecabtagene vicleucel (ide-cel, marketed as Abecma), an FDA-approved chimeric antigen receptor T-cell (CAR-T) therapy, is currently being evaluated in conjunction with subsequent lenalidomide (Revlimid) maintenance in the phase 2 BMT CTN 1902 clinical trial (NCT05032820) for the treatment of patients with multiple myeloma (MM) who had a suboptimal response following upfront autologous stem cell transplant (ASCT) and maintenance lenalidomide. Data from this study were recently presented at 

the 2025 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR

, held in Honolulu, Hawaii, February 12 to 15, 2025, by Alfred L. Garfall, MD, MS, the associate professor of medicine (hematology-oncology) and director of the Autologous Hematopoietic Cell Transplantation, Cell Therapy and Transplant Program at the Hospital of the University of Pennsylvania.

, spoke with Garfall to learn more. In an interview with 

, Garfall explained that, historically, patients who do not achieve a complete response (CR) following ASCT and lenalidomide maintenance do not typically convert to a CR down the line, and noted that for BMT CTN 1902, the investigators projected that this happens in approximately 10% of patients. As such, the primary end point for the study was set as the CR rate at 6 months following ide-cel infusion, with the goal of increasing that rate to at least 30%.

 that 63% of patients (n =38) achieved a CR, and an additional 24% of patients experienced an upgraded response without reaching a CR, leading to an overall response improvement rate of 87%.

With regard to safety, cytokine release syndrome (CRS) was observed in 81.6% of patients, with all cases limited to grade 1 (68.4%) or grade 2 (13.2%). The median time to CRS onset was 1 day (range, 0-4), with resolution occurring at a median of 2.5 days (range, 0-6). Tocilizumab was administered in 77% of cases, and corticosteroids were used in 23% of patients with CRS. Notably, there were no cases of immune effector cell–associated neurotoxicity syndrome observed.

Click here for more coverage of Tandem 2025.

Canonical

Alfred L. Garfall, MD, MS, on Ide-Cel and Lenalidomide Maintenance in MM Following Suboptimal ASCT Response

This article originally appeared on our sister site,

The associate professor of medicine at Medical College of Wisconsin discussed efficacy data presented at the 2025 Tandem Meetings.

Nirav Shah, MD, on Evaluating Zamto-Cel in R/R DLBCL

"Despite some of these poor prognostic indicators, we were happy to report that the overall response rate was [72.8%,] with [50.8%] of patients achieving a complete remission. Many of these remissions were durable."

Zamtocabtagene autoleucel (zamto-cel; MB-CART2019.1), a dual CD19- and CD20-directed noncryopreserved chimeric antigen receptor T-cell (CAR-T) therapy, is currently being evaluated in the 

 for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Interim data from this study were recently presented at 

, held in Honolulu, Hawaii, February 12 to 15, 2025.

, interviewed Nirav Shah, MD, MSHP, an associate professor of medicine at Medical College of Wisconsin, about the analysis, which included 59 evaluable patients in the modified intention-to-treat population. Shah pointed out that many of these patients had elevated International Prognostic Index (IPI) scores and lactate dehydrogenase (LDH) levels at enrollment, indicating high-risk disease. Although, the overall response rate (ORR) was 72.8%, including a complete remission (CR) rate of 50.8%, despite the adverse prognostic factors. Furthermore, an 11.4 month median duration of response was recorded, and for patients achieving a CR, the median duration of CR was not yet reached as of the data cut-off.

At 6 months, the progression-free survival (PFS) rate was 55%, and the median PFS was 9.0 months. The median overall survival (OS) had not been reached.

Shah explained that continued follow-up will be vital to obtain more mature data. Future analyses will examine the 1- and 2-year outcomes for patients treated during the study.

The safety profile of zamto-cel was favorable, with no cases of grade 3 or higher cytokine release syndrome reported. Immune effector cell–associated neurotoxicity syndrome of grade 3 or higher occurred in 4.3% of patients.

Notably, dual CD19/CD20 targeting was associated with a potential mitigation of antigen loss as a resistance mechanism. Among 27 patients who had disease progression, no antigen loss was observed in 22 patients. CD19 loss and CD20 loss were experienced by 2 patients each, and 1 patient had dual CD19/CD20 loss.

Nirav Shah, MD, MSHP, on Evaluating Zamto-Cel in R/R DLBCL

The associate professor of medicine in malignant hematology & stem cell transplantation at Vanderbilt University Medical Center discussed results from a phase 1 clinical trial.

“We did not report any grade 3 or [higher] cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome.”

Poseida Therapeutics is currently evaluating P-BCMA-ALLO1, an allogeneic BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, in an ongoing phase 1/1b clinical trial (NCT04960579) for the treatment of relapsed/refractory (r/r) multiple myeloma (MM). Data from the trial were recently presented at 

, held in Honolulu, Hawaii, February 12 to 15, 2025. The presentation focused on findings from the study's optimized lymphodepletion cohort (Arm C).

Arm C included patients with r/r MM who had been previously treated with at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an antiCD38 monoclonal antibody. The arm allowed for inclusion patients who had previously received a BCMA-directed therapy. In an interview with 

, Bhagirathbhai R. Dholaria, MD, an associate professor of medicine in malignant hematology & stem cell transplantation at Vanderbilt University Medical Center, discussed the results presented at the conference.

The study included 32 evaluable patients in Arm C, and findings demonstrated an overall response rate (ORR) of 88%. Among specific subgroups, patients who were naive to BCMA-directed therapy (n = 16) achieved an ORR of 100% . Those who previously had received 1 or more BCMA-targeted therapies (n = 12) experienced an ORR of 75%, and patients with prior exposure to both BCMA- and GPRC5D-directed therapies (n = 9) achieved an ORR of 78%. Notably, responses were rapid, with a median time to response of 16 days for patients across cohorts A, B, and C. In cohorts A and B, the median duration of response was 214 days; most patients in arm C had been enrolled within 6 months of data cutoff.

Safety data for P-BCMA-ALLO1 in cohort C showed that no cases of grade 3 or higher cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) were reported. Additionally, no patients experienced Parkinsonism, movement disorders, or hemophagocytic lymphohistiocytosis. The overall incidence of CRS was 42%, with all cases limited to grade 1 or 2 in severity. ICANS occurred in 14% of patients, but all events were grade 1 and resolved with minimal steroid intervention.

The hematology-oncology and BMT cell therapy fellow at Stanford University discussed implications of his institution’s findings on treatment-related secondary malignancies.

Mark Hamilton, MD, PhD, on Analyzing PostCAR Myeloid Neoplasms

“One question that we're often asked is whether we should avoid therapy in patients with clonal hematopoiesis mutations, since they can be detected. We don't see any evidence, at least so far, that patients with lymphoma should be denied a life-saving therapy because they have the presence of these mutations prior to infusion. Of course, more work is certainly needed to better define and understand these processes, but as of right now, we find that they're kind of what we would expect.”

 for all chimeric antigen receptor T-cell (CAR-T) therapy products that had been approved by the agency at that time.

 The warnings were related to the potential risk for the development of secondary T-cell malignancies occurring in relation to treatment with BCMA- and CD19-directed genetically modified autologous CAR-T therapy.

In light of these warnings, interest has continued in gaining a better understanding a better understanding of these risks, including the mechanisms behind them and their similarity to other treatment-related risks in oncology. One such study on this topic was presented at at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Mark Hamilton, MD, PhD, a hematology-oncology and bone marrow transplant (BMT) cell therapy fellow at Stanford University.

 The single-institution study evaluated data from a cohort of patients treated with CAR-T therapy for nonHodgkin lymphoma (NHL) at Stanford University.

 held shortly after the conference, Hamilton described the key results of the study and their implications. He pointed out that postCAR myeloid neoplasms seem to derive from preexisting clonal hematopoeisis and occur in patients with high treatment burdens that often have 

 mutations. Hamilton also discussed some of the challenges and limitations of the study, and emphasized that more research on this topic is needed.

REFERENCE
1. FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. April 18, 2024. Accessed February 5, 2025. News release. FDA. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed
2. Hamilton M, Phillips N, Lee D, et al. Single institution analysis of lymphoma treatment related post-CAR myeloid neoplasms. Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract #704

The medical director of the Immune Effector Cell Therapy Program at UCLA discussed initial data from a phase 1/2 trial.

Sarah Larson, MD, on Evaluating Lyell’s CAR-T IMPT-314 in LBCL

“I'm excited to see what the duration of response and progression-free survival are. The follow-up at this point is too short for that to have been presented... I'll be excited to see that [because] the CD62L-selected cells we would expect to have better persistence, which we would hope then translates into a longer duration of response and progression-free survival.”

Currently, a number of chimeric antigen receptor T-cell (CAR-T) therapies are commercially available for the treatment of large B-cell lymphoma (LBCL). Although, a number of companies and academic institutions are continuing to develop new CAR-T products for this indication, with innovations intended to provide new alternatives and overcome limitations of the current treatment options. One such product is Lyell Immunopharma’s IMPT-314, a CD19/CD20 dual-targeted autologous CAR-T therapy, which is currently being evaluated in a phase 1/2 clinical trial (NCT05826535) for the treatment of relapsed/refractory LBCL in patients who have not previously received CAR-T therapy. Initial results from patients treated in this trial were recently presentedat the

, held December 7-10, 2024, in San Diego, California, by Sarah Larson, MD, the medical director of the Immune Effector Cell Therapy Program in the Division of Hematology/Oncology at David Geffen School of Medicine at University of California, Los Angeles (UCLA).

Shortly after the close of the conference, 

 interviewed Larson to learn more. Larson discussed the rationale behind the design of IMPT-314, and then went over the key results that were presented, highlighting that among 17 patients evaluable for efficacy, the overall response rate was 94% (16/17), with a complete response rate of 71% (12/17) by 3 months posttreatment. In terms of safety, she noted that the toxicity profile was favorable, with no grade 3 or higher cytokine release syndrome reported, and cases of immune effector cell-associated neurotoxicity syndrome (ICANS) predominantly being grade 1 to 2. Larson also spoke about potential future plans for IMPT-314, and pointed out that the clinical trial is currently recruiting patients.

REFERENCE
1. Lyell presents positive initial clinical data from the phase 1-2 clinical trial of IMPT-314 for the treatment of B-cell lymphoma at the 2024 ASH annual meeting. News release. Lyell Immunopharma, Inc. December 9, 2024. Accessed January 23, 2025. https://ir.lyell.com/news-releases/news-release-details/lyell-presents-positive-initial-clinical-data-phase-1-2-clinical

This is the third part of an interview with Manali Kamdar, MD. For the second part, 

The clinical director of lymphoma services at the University of Colorado discussed the importance of referring patients who are transplant ineligible for CAR-T treatment.

Manali Kamdar, MD, on Transplant Eligibility Versus CAR-T Eligibility

“Please if you think of a [patient with] refractory, diffuse LBCL in the second line setting or third line setting, please refer them to a CAR-T academic center or a community site capable of doing CD19 CAR-T ASAP because it is really of the essence to get the patient to a CAR-T physician. As you know, manufacturing time has to be accounted for, and for now, I can say the only cure I know of, which is the new standard of care, would be a CD19 CAR in the second line as well as in the third line setting.”

One of the key early line treatment options for patients with hematologic malignancies such as large B-cell lymphoma (LBCL) is allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Although allo-HSCT has the potential to be curative, unfortunately some patients are ineligible to receive it, because of factors such as advanced age or a frail constitution that may put them at too high of a risk to endure the potentially serious adverse events (AEs) associated with allo-HSCT. In the second and third line settings for relapsed/refractory (r/r) LBCL, autologous chimeric antigen receptor T-cell (CAR-T) therapy, such as the CD19-directed lisocabtagene maraleucel (liso-cel, marketed as Breyanzi by Bristol Myers Squibb), can serve as another potentially curative option for patients. Because CAR-T also has certain potentially serious AEs associated with its use, some healthcare providers are inclined to equate allo-HSCT ineligibility with CAR-T ineligibility.

, Manali Kamdar, MD, the associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado, argued against this trend as an addendum to a larger discussion about results from the TRANSCEND-NHL-001 clinical trial (NCT02631044) evaluating liso-cel that were presented at the

, held December 7-10, 2024, in San Diego, California. Kamdar emphasized her view that some patients traditionally deemed ineligible for allo-HSCT are perfectly capable of receiving CAR-T safely, and that such patients should be referred to a center capable of providing CAR-T as soon as possible in order to ensure better treatment outcomes.

REFERENCE
1. Abramson JS, Palomba ML, Gordon LI, et al. Five-year survival of patients (pts) from Transcend NHL 001 (TRANSCEND) supports curative potential of lisocabtagene maraleucel (liso-cel) in relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract 3125

The clinical director of lymphoma services at the University of Colorado discussed the importance of referring patients with r/r LBCL who are transplant ineligible for CAR-T treatment. 

The last thing that I might add is something that’s decidedly nonimmunologic and that’s that I think we really have to make sure, as a field, and I think this has to be a collaboration between developers and physicians and even payers, both government and private payers, is to make sure that we have access to these therapies.

One of the things that I’ve seen and have been increasingly thinking about is systems and how we succeed is a troubling trend that, first, not everybody has equal access in this country. That’s dictated by racial and socioeconomic and structural features as well as in part by the cost of these therapies and the difficulty of getting them to people. And as we look at individuals, for example, who have received all T-cell therapies including giving CAR T therapies, you start to see more skewing; in other words, traditional factors that affect access, whether it’d be racial or socioeconomic, tend to be exaggerated as we have these high-cost complex technologies that require not being treated in the rural center where you live but getting to an expert like you or me at the H. Lee Moffitt Cancer Center, Tampa, Florida or UCSF [University of California, San Francisco] where you have to take some effort to get there. And it’s going to be harder. Individuals who historically had access barriers whether culturally, educationally, or economically are less likely to get to us.

I would say you’re absolutely right. I don’t think I can add to your thoughtful summary of the immunologic issues, but I want to make sure as we move forward that we do everything we can to make sure that these therapies, which are breakthrough therapies, are keeping people alive longer, already in clinical trials, and will do so even more once they’re approved, get to everybody, and that we work as hard as we can in a collaborative way to make that happen.

I think that’s a great way to end this session. I’d like to thank 

®for having afforded us the opportunity to get TIL [tumor-infiltrating lymphocyte] cell therapy to the forefront. And I’d like to thank my colleague, Krishna Komanduri MD, for sharing his excellent expertise.

Thank you. My brilliant pleasure, and I want to join you in thanking the 

® group and our audience for paying attention this long. Thanks so much.

Closing out their discussion on TIL therapy, Drs Sarnaik and Komanduri identify existing barriers to TIL use in clinical practice and how the field might optimize patient access to these regimens.

Overcoming Barriers to TIL Use in Patients With Solid Tumors

Well, that’s a great segue into our final topic, and that involves future directions. Are there any interesting ongoing either trials or data or concepts that you look forward to seeing with regards to the TIL [tumor-infiltrating lymphocyte] space?

I would say the first thing is that we shouldn’t underestimate the importance of this moment. I mean, it’s been a long time coming. We’ve been talking about cell therapies and gene therapies for a long time, axi-cel [axicabtagene ciloleucel], tisagenlecleucel, and ide-cel [idecabtagene vicleucel] have been absolutely transformative in the setting of CD19 diseases. And lately, we have really remarkable successes in the context of BCMA [B-cell maturation antigen] approaches and now we have TIL therapies. I do think one of the things that we’re going to have to look for is how therapies that require bespoke manufacturing like CAR [chimeric antigen receptor] T-cells and TIL therapy are going to compete with therapies that can quite easily be manufactured at scale like bispecific antibodies that may not have quite the success that TIL therapies or CAR T-cell therapies have, but are a lot easier to manufacture and might not have or won't have, I think, the downside associated with treatment delays.

I think that we’re in a setting and we’re starting to see this in areas like myeloma where we’ve just had a number of dramatic advances. We went from immunomodulatory therapies to proteasome inhibition therapies. Now, we have bispecifics and CARs all competing with other pharmacologic agents. In melanoma, of course, we still have targeted agents that can interfere with MAP [mitogen-activated protein] kinase and MEK [mitogen-activated protein] signaling, for example. I think one of the curious things that we’re going to have to see is how do we as a field come together, sequence therapies, use combination therapies generally as immunologists.

I think that we’re going to be moving further toward combination therapies. And yet those trials are hard to do. These agents are expensive individually, and they’re even more expensive together. So how do we do that and appropriately ask questions as a field in ways that we’re not stepping on each other’s toes and competing with each other as we do these trials? I think that’s going to be a real challenge. I know that that’s not a direct answer to where are we going but I think in a way we have amazing successes and new approved therapies coming and that’s going to create challenges for us as academicians to figure out how to do that. I’m curious if you have any thoughts on that topic or if you can see other obvious directions that we’re going to go in.

I think one of the interesting points you raised is that there’s going to be a lot of competition between agents and how to sequence. I think also how to attribute biological response to the actual agent in question and what I mean by that is it’s good news that our patients are now living much longer with advanced melanoma than 10 years ago. But what you notice is that some of the efficacy may be additive. Somebody gets a PD-1 antibody, and they progress, there still may be a lingering biological effect of that PD-1 antibody because it’s not the PD-1 antibody that’s exerting the response, it’s the effect of the PD-1 antibody on the immune cell. So unlike chemotherapy, where it’s a nonspecific poison and it only works for as long as the drugs in the patient system, immunotherapy is not like that at all.

And I think one of the things that we do need to develop are surrogates for response, readout assays that are beyond just scanning the patient or functional path, or immunologic assays to detect and track a specific antitumor immunologic response from your treatment. And I think if we’re able to do that, we should be able to logically sequence our patient treatment. And we may be able to do that in a patient-specific way. I think we’re still a bit primitive in our clinical trial design where we take a group of 100 patients and treat them not really understanding that well maybe some portion of that patient population would respond to one treatment better than another. If we’re able to build better readout assays to predict which treatment modality would give the best biological effect, that’ll come a long way for us.

The last thing I wanted to mention, tying it back into some of these preclinical abstracts that we’ve discussed, I do think that improving the efficacy of cell therapy on a per cell basis may have a couple of advantages. Number 1, we may not need to treat patients with such large number of TILs that we’re doing now. I think that is one distinction between CAR T and TIL is that CAR T uses a much smaller number of cells and TIL does and in part it could be the target of your CAR T is a lot more amenable than it is for melanoma or non-small cell lung cancer because you need the TIL to traffic outside of the blood supply which you don’t need for CAR T-cell therapy.

And secondly, the need for such intensive lymphodepletion. If we have more potent T cells, we may be able to attenuate or even do away with the lymphodepletion and that would result in our being able to treat more patients and possibly also give repeated cycles of therapy. Right now, we’re limited in our cycles of therapy because the lymphodepletion can cause some permanent bone marrow fibrosis and bone marrow failure. But if we get tumor-specific TIL, we won’t get the on-target off-tumor effect and then we’ll also get the ability for improved efficacy. What are your thoughts about that?

Well, first I’d say, no I consider myself card-carrying immunologist. I don’t think I could do much better than you just did, so I won’t try and riff on what you just said. I think all those things are really critical.

Experts Amod Sarnaik, MD, and Krishna Komanduri, MD, consider lessons learned about TILs and CAR T-cell therapy in hematologic cancers, and how they anticipate TILs fitting into treatment paradigms for solid tumors.

Oncology

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