In addition, liso-cels distinct manufacturing process creates a defined composition of CD8+ and CD4+ T-cells, which may reduce product variability; however, the manufacturer states, the clinical significance of defined composition is unknown.
For insights on what the arrival of liso-cel could mean in the treatment landscape, The American Journal of Managed Care (AJMC) turned to Tanya Siddiqi, MD, director of the Chronic Lymphocytic Leukemia Program at Toni Stephenson Lymphoma Center and associate clinical professor, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, Duarte, California.
Siddiqi was an investigator for ZUMA-1, which led to the approval of axicabtagene ciloleucel(axi-cel), sold as Yescarta, and the TRANSCEND NHL trial for liso-cel.She has addressed major scientific meetings on the challenge of managing the toxicities associated with CAR T-cell therapyand discussed how liso-cel represents a step forward over its predecessors.
This interview, conducted before the BMS announcement, has been edited for clarity and length.
AJMC: We're anticipating an FDA decision on liso-cel before the end of the year. Can you discuss the need of the patients who would take this new CAR T-cell therapy?
Siddiqi: So, for CAR T-cell therapy targeting CD19-positive B-cell lymphomasspecifically aggressive B-cell lymphomaswe already have a couple of FDA-approved options. The question is: what is liso-cel? How is it different? Why would people pick this over other things? In the trials that we've conducted, we found that liso-cel seems to have lesser toxicity in terms of the specific CAR T-cell side effects of cytokine release syndrome or hyper-inflammation, as well as neurotoxicity. We've just seen fewer severe adverse events so much so that at some [cancer] centers across the country, weve been able to give liso-cel CAR T-cells to patients in the clinic or outpatient setting rather than having to admit them to the hospital , depending on the patient's situation.
Those are the strengths of liso-celless toxicity and thus, a better chance of giving it in the outpatient setting with hospital admission available to anyone who develops a fever or other side effects. This means fewer days of inpatient hospitalization for these patients, so it may be less costly overall. I dont think the efficacy is necessarily differentmeaning that it seems to work as well as the other FDA-approved products already commercially available. But for the reasons that I've listed, I think it might be a very good option for older patients, maybe patients who are bit more frail, or younger patients who just don't want to be admitted to the hospitalthey just want to try to do it in the outpatient setting.
AJMC:You touched on this already, but can you discuss how Iiso-cel differs from earlier CAR T-cell therapiesboth in the way it's manufactured and how it works, and what that reduced variability means for patients?
Siddiqi: Liso-celis manufactured in a way that it gives very precise, equal numbers of CAR cells that are labeled CD4 and CD8, in a 1:1 ratio. All of us have T cells to fight infections with, and these T cells are what we take from patients. Then, we modify them in the lab by genetic engineering in order to produce CAR T-cells so that now instead of looking for infections, these CAR T cells are going to look for B-cell lymphoma cells and fight lymphoma.
The other products are given back to patients as a bag of CAR T cells mixed with potentially varying ratios of different types of T cellsCD4+, CD8+, etc. With liso-cel the manufacturing process actually separates out the CD4+ and CD8+ types of T cells first, and then manufactures CAR-T cells out of them separately. So, when we give the cells back to patients, we give it in a 1:1 ratio of CD4+ and CD8+ cells. We know exactly how many CD4+ and how many CD8+ T-cells these patients receive. And the thought is, the researchers and the drug manufacturer feel that this helps to have an expectation of what expansion you will have of these cells in the body.
Therefore, we potentially have an idea of what type of side effects or how severe the side effects might be. It may limit some of those side effects, or at least make them a little bit more predictable or controlled.
AJMC:Thats a great way to shift to your own work on length of stay due to CRS. What do we know about the key variables in determining whether a patient will experience a side effect that requires an extended stay in the hospital, and can more be done to avoid lengthy hospital stays?
Siddiqi: That's a very important question. Because lengthy hospital stays, especially in the [intensive care unit], really adds to the bill and the financial burden of these treatments. We know that people who have a big burden of disease going into CAR T-cell therapy, meaning they have a lot of lymphoma in their bodies, they tend to be at higher risk for more side effects like cytokine release syndrome and neurotoxicity. Probably because there's so much inflammation thats generated while these CAR T-cells are trying to fight the lymphoma. What we know is that people who come to us for CAR T-cells with lesser disease might have fewer side effects potentially and a better overall outcome.
So, we always try to advise our referring physicians, and educate patients, at conferences, to try to send these patients to us before they are at the end of the linebefore theyve tried and failed everything, and now theres just rampant disease. [At that point,] you're dealing with a situation where the patient is going to have more side effects and will not be able to tolerate the CAR T cells as well. Instead, if they fail two lines of therapy and the disease is still small in volume, but it's starting to progress, we can treat them more effectively with CAR T cells and with fewer side effects potentially.
AJMC:That brings up the next topicthere have been discussions that CAR T-cell therapy should be given earlier during treatment. As you said, if its not given as the last resort, patients might respond better. Where do you see those patterns heading in the future? And would that be truer for some patients than others?
Siddiqi: With aggressive diffuse large B-cell lymphoma, there's about a 60% to 70% chance of curing that in the frontline setting. With the line of chemo-immunotherapy, you can cure 60% to 70% of patients so that it never comes back. But the rest of themwhen it just relentlessly keeps coming back and it's hard to cureonce those patients relapse they tend to keep relapsing. So, our mainstay in the relapse setting is to give them salvage chemo-immunotherapy, collect stem cells, and take them to autologous stem cell transplantation if they've achieved a remission with the salvage chemotherapy. If they haven't achieved remission with that salvage chemotherapy, then they should go on to CAR T cells directly instead of waiting and trying more and more chemotherapies. After failing second line therapy, the FDA approval allows us to try CAR T cells. There are studies that are now ongoing that are comparing CAR T cells to autologous stem cell transplantation after failing first line therapy. So, once patients relapse the first time, these studies are comparing giving them salvage chemotherapy and transplant, versus taking them straight to CAR T cells. Once we have that data, we'll know better whether we can do CAR T cells even earlier in the lines of therapy.
AJMC:Weve been hearing for some time more about allogeneic or off-the-shelf therapies. What progress has been made on in that technology?
Siddiqi: I'm not too involved with these trials myself, but I know we have trials at City of Hope that are ongoing with off-the-shelf therapy. What I can tell you is that it's very attractive in that you don't have to collect T cells from patients, keeping their lymphoma under control while these T cells then go to the lab and CAR T cells are manufactured in 2-4 weeks depending on which product it is, and then they come back and get infused. With off-the-shelf products, you can just grab it and go as soon as you know the patient needs it.
The initial concerns were because the cells are not from the patient themselvesthe cells are from donors. Across the board there might be concerns of rejection and what's called graft-versus-host disease and things like that. So far, I don't think in the trial they've come up with such side effects to any significant extent. What I don't know is whether they've come up with a good result yet. Is it looking like the benefits of taking off-the-shelf CAR T cells are as good as autologous CAR T cells, meaning patients own CAR T cells? I think that remains to be seen. If they are, then it's much easier to use off-the-shelf CAR T cells. Maybe at the American Society of Hematology annual meeting in December we will see more data.
AJMC: How is COVID-19 affecting the clinical trial process for CAR T cell therapy?
Siddiqi: When the pandemic kind of started surging early in the year, and when we went into lockdown mode from March onward, we and other centers across the country took a lot of steps to slow down our clinical trial enrollment. Our staff started staggering who would come into work which day of the week and who could work from home. For those in the clinical trials office, there was a lot of need for safety and logistical reasons for us to slow down enrollment onto clinical trials. And there were other questions, such as, who would take care of patients at home once we discharged them after they received CAR T cells? What if their caregivers were exposed and got sick? Logistically, it was difficult to safely do many trials, especially CAR T cell trials and transplants earlier in the year.
Since the end of summer, we ramped up again, and we're now doing as many transplants and CAR T cells as we were probably doing last year. So, we're pretty much all the way up again, but I don't know how this winter will go because COVID is surging again.
As far as just CAR T cells themselves, we had to also think about travel for the cells because Juno Therapeutics is in Seattle, and Kite Pharma is here in Los Angeles, but Novartis is elsewhere. Just the movement of these cells was a concern because of travel restrictions during COVID-19. But as far as I know, the companies did not lose that commitmentthey told us, well get the cells to you, we will find a way to do it. I don't think any patients went without cells who should have received cells.
AJMC: What advice do you have for community oncologists interested in CAR T cell therapy for their patients?
Siddiqi: Theres good news for community physicians. We may soon have a therapeutic option of liso-cel CAR T cell therapy which seems to have lesser side effects. So, this might make things cheaper due to less need for hospitalization potentially without compromising the chance of cure. We want these patients to try CAR T cell therapy sooner rather than later in their relapses. You can always try multiple cycles of chemotherapy at some other time if you relapse again, but if you can be cured with CAR T cells such that you never need treatment again, why not try that first? For the patients who respond well to CAR T cells, the treatment works extremely well. And that's the Holy Grail to find the cure for all patients.
Maybe only half the patients will currently have a very good and durable responsebut those patients may never relapse again. So why not try it sooner rather than later? And of course, we're always looking for trial patients, because now we need to improve these results even further. So, community oncologists should also refer for trials, because I think that its very important to have trials with different combinationsCAR T cells plus another immunotherapy agentto see if we can improve upon the response rates even more.
Go here to see the original:
Tanya Siddiqi, MD, Discusses the Promise of Reduced Toxicity With Liso-Cel - AJMC.com Managed Markets Network
- 'Natural Killer Cells' and Other Promising Cancer Treatments - Barron's - April 18th, 2021
- Capturing the Pandemic Experience in Haiku Poetry - Duke Today - April 18th, 2021
- Chemotherapy for Prostate Cancer: When It's Used and What to Expect - Healthline - April 18th, 2021
- Signs that Chemo Is Working: How Effectiveness Is Measured and Defined - Healthline - April 18th, 2021
- Some experts fear next-generation Covid vaccines may be worse - STAT - April 18th, 2021
- How Long is Chemotherapy? What to Expect - Healthline - April 18th, 2021
- Regenerative Medicine - Stem Cell Therapy Little Rock - March 8th, 2021
- Center for Stem Cell Biology & Regenerative Medicine ... - March 8th, 2021
- Dynamic Stem Cell Therapy Offers Regenerative Medicine - Las Vegas Review-Journal - March 8th, 2021
- Anti-EGFR VHH-armed death receptor ligandengineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers -... - March 8th, 2021
- Research Antibodies Market Size to Reach USD 5325.8 Million by 2027 | Increasing R&D Activities in the Fields of Oncology, Neurobiology, and Stem... - March 8th, 2021
- Microwave Processing Isolates Red Ginseng Compounds That Suppress Lung Cancer Metastasis - Genetic Engineering & Biotechnology News - March 8th, 2021
- Longeveron Expands Enrollment Criteria for its Phase 1 RECOVER Trial Evaluating Lomecel-B Infusion to Treat Acute Respiratory Distress Syndrome due to... - March 8th, 2021
- Be The Match BioTherapies Announces Expansion of Multi-Year Strategic Alliance with Orchard Therapeutics to Support European Commercial Launch of... - March 8th, 2021
- Autologous Stem Cell and Non-Stem Cell Based Therapies Market 2021: Focuses at the key worldwide companies to Define, Describe and Analyses the sales... - March 8th, 2021
- Editing Reproduction: CRISPR and preventing heritable diseases, With Dr. Dietrich Egli and Dr. Sam Sternberg - Columbia University Irving Medical... - March 8th, 2021
- U. Cancer Center pilot projects: investigating cancer connections - The Brown Daily Herald - March 8th, 2021
- COVID-19 can kill heart muscle cells, interfere with contraction Washington University School of Medicine in St. Louis - Washington University School... - March 8th, 2021
- Vaccinating by age groups is unfair, particularly to minorities, advisory panel tells CDC - USA TODAY - March 8th, 2021
- Winter Weather Impacting Blood and Platelet Donations - Milwaukee Community Journal - February 17th, 2021
- Joshua Shirk continues to fight the odds; mom says God placed people where they needed to be to help him - Keyser Mineral Daily News Tribune - February 17th, 2021
- Evotec and Medical Center Hamburg-Eppendorf Enter Partnership to Develop iPSC-Based Tissue Therapy for Heart Failure - GuruFocus.com - February 7th, 2021
- ProgenCell - Stem Cell Therapies offers an updated Stem Cell Therapy for Anti Aging Protocol - PR Web - January 30th, 2021
- Doctors urge immunocompromised to get COVID vaccine when it becomes available - KMTV - 3 News Now - January 30th, 2021
- Autologous Stem Cell and Non Stem Based therapies Market Share, Size 2021 Global Industry Future Trends, Growth, Strategies,, Segmentation, In-depth... - January 30th, 2021
- Studies Indicating T-Cells May Be Needed For Long-Term Protection From The SARS-Cov-2 Virus - PRNewswire - January 30th, 2021
- Researchers use patients' cells to test gene therapy for rare eye disease - National Institutes of Health - January 30th, 2021
- Two Gene Therapies Fix Fault in Sickle Cell Disease and -thalassemia - MD Magazine - January 30th, 2021
- If I Have Cancer, Dementia or MS, Should I Get the Covid Vaccine? - Kaiser Health News - January 30th, 2021
- L-MIND Trial Results Show CD19 Antibody Is Reasonable in R/R DLBCL - Targeted Oncology - January 30th, 2021
- Profile of T Cells, Broadly Neutralizing Antibodies, Anti-Viral Targets: COVID-19 Updates - Bio-IT World - January 30th, 2021
- HealthLynked's The Future of Healthcare Summit Brings Healthcare Experts and Technology Innovators from Around the World to Naples, Florida - WFMZ... - January 30th, 2021
- Tevogen Bio Secures Funding from Team of Doctors to Support Clinical Trials of Its Investigational Curative T Cell Therapy for COVID-19 - PRNewswire - January 25th, 2021
- Novel Treatment Leads to Dog's Recovery - The Bark - January 25th, 2021
- Identification and Targeting of ThomsenFriedenreich and IL1RAP | OTT - Dove Medical Press - January 25th, 2021
- Regenerative Medicine Market Size Worth $74831.35 Million With CAGR of 22.27% By 2024 | Segmented by Product Type, Top Manufacturers, By End-User... - January 25th, 2021
- Immunotherapy Inches Forward in Development of Myeloid Malignancies - OncLive - January 14th, 2021
- Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid... - January 14th, 2021
- Kaleido Biosciences Announces Positive Interim Results of Controlled Study of KB109 in Patients with Mild-to-Moderate COVID-19 - BioSpace - January 14th, 2021
- Doctors Make Medical Breakthrough In Treating Severe Cases Of COVID - CBS San Francisco - January 9th, 2021
- Mana joins the hectic fight against solid tumors with an 'off-the-shelf' candidate angling for an IND this year - Endpoints News - January 9th, 2021
- Versiti Blood Centers and Noodles & Company Serve Up Thanks to Blood Donors - PRNewswire - December 31st, 2020
- Global CAR-T Pipeline Insight Report 2020: Overview, Landscape, Therapeutic Assessment, Current Treatment Scenario and Emerging Therapies -... - December 31st, 2020
- 2020 health care year in review - Crain's Cleveland Business - December 31st, 2020
- The Top 10 FDA Oncology Drug Approvals of 2020 - Curetoday.com - December 31st, 2020
- Gut microbiota: How does it interact with the brain? - Medical News Today - December 31st, 2020
- Numerous Indian American STEM Researchers Named Fellows of American Association for the Advancement of Sciences - India West - December 31st, 2020
- Four years after devastating spinal injury, former St. Paul's football player reunites with caregivers - NOLA.com - December 24th, 2020
- New Combination Therapy Tested By Children's May Offer Hope For Leukemia Patients - WVXU - December 24th, 2020
- Real-time observation helpful in Stem cell for vascular diseases: Study - Hindustan Times - December 21st, 2020
- NurOwn May Be Given to Early ALS Patients in US Who Finished Phase... - ALS News Today - December 21st, 2020
- Follow the Money: Spatial Omics, CAR-NK Cells, AI-Powered Biology - Bio-IT World - December 21st, 2020
- Explained: Process of transporting stem cell from donor to patient for a successful transplant - Firstpost - December 18th, 2020
- Research That Saves Lives: Four COVID-19 Therapies Being Tested at UVA - University of Virginia - December 18th, 2020
- Even if You've Had COVID-19 You Still Need the Vaccine - Healthline - December 18th, 2020
- What Patients With Cancer, Survivors Need to Know About the Emergency Use Authorization of COVID-19 Vaccine - Curetoday.com - December 16th, 2020
- 2020 at the U: The year in review - University of Miami - December 16th, 2020
- Five Mobile County hospitals to get Pfizer vaccine this week - AL.com - December 16th, 2020
- Donor Stem Cell Transplant Improves Survival in Older Patients with Myelodysplastic Syndrome - Cancer Health Treatment News - December 10th, 2020
- Positive Phase 2 Proof-of-Concept Data for Viralym-M and Burden of Disease Data Presented in Oral Presentations at the 62nd American Society of... - December 10th, 2020
- Dr. Kansagra: Quadruplet Therapy for Newly Diagnosed Multiple Myeloma and Combination CAR T-Cell Opportunities - DocWire News - December 10th, 2020
- Silicon Therapeutics Announces Members of Scientific Advisory Board - Business Wire - December 10th, 2020
- Israeli Neurogenesis' NG-01 slows progressive MS by up to 90% in phase II study - BioWorld Online - December 10th, 2020
- ADC Therapeutics Announces Updated Clinical Data on Lead Antibody Drug Conjugate Programs Loncastuximab Tesirine (Lonca) and Camidanlumab Tesirine... - December 10th, 2020
- Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145... - December 8th, 2020
- Precigen Presents New Data Supporting the Safety, Clinical Activity, Expansion and Persistence of PRGN-3006 UltraCAR-T at the 62nd ASH Annual Meeting... - December 8th, 2020
- ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma - Cancer Network - December 8th, 2020
- Rocket Pharmaceuticals Presents Positive Clinical Data from its Fanconi Anemia and Leukocyte Adhesion Deficiency-I Programs at the 62nd American... - December 8th, 2020
- Negrin Shines Light on the Orca-T Story in GVHD - OncLive - December 8th, 2020
- Preliminary Results from NexImmune's Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition - GlobeNewswire - December 8th, 2020
- BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute... - December 8th, 2020
- Sutro Biopharma Presents Data from Ongoing Phase 1 Dose-Escalation Study for STRO-001 for the Treatment of B-cell Non-Hodgkin Lymphoma at the 62nd... - December 8th, 2020
- Data from the ANDROMEDA Study Show Hematologic Response for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in Newly Diagnosed Light Chain (AL)... - December 8th, 2020
- US FDA Approves Naxitamab for the Treatment of Neuroblastoma - OncoZine - November 29th, 2020
- Coronavirus treatments and vaccines. Here are the latest developments - San Francisco Chronicle - November 29th, 2020
- Dr Apar Kishor Ganti Outlines the Effectiveness of Lurbinectedin and Benefits Over Competition - AJMC.com Managed Markets Network - November 26th, 2020
- Commonly used antibiotic shows promise for combating Zika infections - National Institutes of Health - November 26th, 2020
- A real life Superman celebrates 5 years of survival from one of the deadliest cancers - Newswise - November 26th, 2020
- Global Cell Harvesting Market to Reach US$381,4 Million by the Year 2027 - Salamanca Press - November 26th, 2020
- Tetracycline-based Antibiotics Show Promise for Combating Zika Infections - Global Biodefense - November 26th, 2020