Orca-T Offers an Alternative to HSCT With Improved Patient Experience – OncLive
By daniellenierenberg
Advances in the treatment of patients with leukemias and lymphomas have led to a significant improvement in survival, which has increased the need for bone marrow transplant as a later-line therapy, said Mehrdad Abedi, MD, who added that Orca-T, a high precision cell therapy, confers significant antitumor activity, minimizes the incidence of acute and chronic graft-vs-host disease (GVHD), and causes less adverse effects (AEs) compared with standard bone marrow transplant among these patients.
There is a lot of research [ongoing]; the holy grail of research is trying to figure out whether we can separate the graft-vs-leukemia or graft-vs-lymphoma effect from GVHD, said Abedi. [The Orca-T trial] is basically looking at the past 10 years of research in this area to try to identify the cells that are good from those that are bad.
During the 2021 Transplantation and Cellular Therapy (TCT) Meetings, findings from an analysis of 2 studies demonstrated a significant reduction in cases of GVHD, a higher GVHD relapse-free survival rate, and a lack of treatment-related mortalities with Orca-T when historically compared with hematopoietic stem cell transplant (HSCT).
Additionally, the median time to neutrophil engraftment, median time to platelet engraftment, and median time from day 0 to hospital discharge was shortened with Orca-T compared with HSCT.
In an interview with OncLive during the 2021 TCT Meetings, Abedi, a professor of cancer, hematology/oncology, and internal medicine in the Department of Internal Medicine, Division of Hematology and Oncology at the UC Davis Comprehensive Cancer Center, discussed the challenges of standard transplant, how Orca-T could overcome some of those limitations, and the potential future of transplant in hematologic malignancies.
Abedi: HSCT has been around for more than 50 years in one form or another. It has been used mostly for patients with blood cancers, [such as] leukemia and lymphoma. Allogeneic bone marrow transplants, where we use cells from a donor, are very effective. [They are associated with] a very high response rate for patients who have no other options and whose disease is going to [recur] without transplant.
The problem [with allogeneic bone marrow transplant] is that it [is associated with] AEs. When we give donor cells to patients after high-dose chemotherapy, [which is given] so that the patients body doesnt reject [the cells], even though the cells are a match for the patient, they can still [develop] severe GVHD.
The acute form of GVHD can be life threatening, whereas the chronic form can become a nuisance for the rest of a patients life. A lot of patients suffer [from GVHD] to the point where they regret going through transplant. Fortunately, that is not everybody, but it is still a problem that needs to be solved and an unmet need for the field.
This research has been focused on [the question of]: Are there specific cells in the graft we give to the patients immune cells that can cause GVHD? Can we separate those cells from those that are responsible for causing graft-vs-leukemia effects?
Basically, Orca Bio approached UC Davis a few years ago to [start] collaborative research with our Good Manufacturing Practice [GMP] facility and to produce these products.
Each graft of [the Orca-T] product has stem cells and immune cells in it. The stem cells are what we need to maintain the graft and [allow the product to] stay in the patient for a long time. The immune cells are the ones that can cause graft-vs-leukemia [effects], which is what we want.
From the work that Robert Negrin, [MD] at Stanford University and many other investigators [did], it is very clear that there is a population of T cells called T-regulatory cells that can prevent GVHD. There are other populations, such as the nave T cells or conventional T cells that can cause GVHD. It looks like a smaller number of [those cells] may actually be helpful; they can cause graft-vs-leukemia, but not GVHD.
The graft is basically designed so that we can give stem cells, but they get rid of a lot of conventional T cells that can cause rapid GVHD. [The graft provides] a small amount of conventional T cells that can cause graft-vs-leukemia effects, as well as the regulatory T cells that can prevent GVHD. UC Davis got involved [with this work] because we have a very robust GMP facility. We helped Orca Bio design these protocols and manufacture the cells. Now, [Orca Bio] has moved on to their own facility. I have been involved [with this research] for the past few years.
[We] havent looked at the QOL data, but there have been several short-term and long-term benefits so far that we have seen.
We give high-dose chemotherapy that can get rid of all [the patients] stem cells and leukemia or lymphoma cells. Then, we give the graft; however, after the graft is given, it takes a couple of weeks usually to engraft [before] new cells [develop]. In between, the patients are sick because of the effects of the chemotherapy; patients also have low blood counts.
[With Orca-T] we have seen that the engrafting [occurs] a little bit earlier. For everyday [sooner] the engraftment [occurs], there is less risk of complication and suffering for the patient. That has been a major difference [with Orca-T].
Also, we have noticed that patients in general are doing better [with Orca-T compared with traditional transplant]. When we give high-dose chemotherapy, it is the same whether the patient is on a clinical trial or not. They may still get sick [with Orca-T] because of the effects of chemotherapy.
However, there is also inflammation [that can occur] as the donor cells are trying to establish themselves in the body because some of them attack the body. That inflammation also adds to the problems with chemotherapy. We havent seen that inflammation [with Orca-T]. We have seen some effects from the chemotherapy, but because we dont have the inflammation, other AEs that we see with the standard of care arent seen with Orca-T.
In general, patients do better [with Orca-T vs standard of care], and that has been a universal experience with all of our patients who have gone through the trial so far.
[Patients] just look and feel better. When they are discharged, they are not as sick compared with patients [receiving] the standard of care.
With the standard of care, after we give the graft, we have to give patients a new medication to prevent GVHD because it is such a lethal problem. If we dont put patients on immunosuppressive medications to prevent GVHD, there is a very high chance that they get and die from GVHD. Those immunosuppressive medications are critical.
The way the Orca-T graft is designed is that we dont need as many of those [immunosuppressive] medications. For example, there is a medication called methotrexate that we give on days 1, 3, 6, and 11 after [standard] transplant. That medication can cause a lot of other AEs, such as mouth sores, delayed engraftment, and kidney [problems], that can make the patient miserable. With Orca-T, we dont have to [give methotrexate], which by itself is a huge improvement.
We do give immunosuppressive medications, such as tacrolimus [Envarsus XR] or sirolimus [Rapamune] to these patients, but we dont give 2 or 3 medications as we usually do with the standard of care. Less immunosuppressive medications mean probably less infection, but more importantly, less AEs. Thats [a factor that has made] a big difference in patient experience.
That is a very loaded question. There are a lot of new drugs coming, some of which are very targeted to treat leukemia or lymphoma. Thus far, we havent seen any curative [benefit] with those drugs, so in most situations, we will still need an allogeneic stem cell transplant for patients.
The exceptions [to that] were rare diseases, such as chronic myeloid leukemia [CML], where [an oral medication was approved] and we dont need to transplant patients. That is an example of a targeted treatment that may exclude [the need to] transplant patients. That would be great because transplant is not a trivial procedure and it has a lot of AEs.
However, [CML] is a very specific disease with 1 gene that causes the disease. In most leukemias and lymphomas, multiple genes are involved, so we dont think single-target treatments will get rid of the disease. We still think that allogeneic transplant will be around for a long time.
In fact, if you look at any center in the country, the volume of transplant has substantially increased over time because patients are living longer. Patients end up being able to go to a transplant vs before when many were dying in the middle of their treatment and not getting to transplant.
That being said, there are 2 directions [we can go in]. One is to try to decrease the AEs associated with transplant. This [Orca-T cell therapy] is very effective [in doing this] by targeting the graft-vs-leukemia effect and preventing GVHD. The second direction is to use these allogeneic cells to specifically target the tumor cells. That is why gene modifications, CAR T-cell therapies, and other approaches are coming. They still use allogeneic cells from a donor, but now they are directing them to specifically go after tumor cells.
Go here to read the rest:
Orca-T Offers an Alternative to HSCT With Improved Patient Experience - OncLive
- 001 Expansion of Stem Cells by Valproic Acid [Last Updated On: June 24th, 2011] [Originally Added On: June 24th, 2011]
- 002 Cord Blood and Bone Marrow Stem Cells for Liver Failure [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- 003 Science behind Enhancing Adult Stem Cells for wellbeing [Last Updated On: June 26th, 2011] [Originally Added On: June 26th, 2011]
- 004 Stem cells Transplatation in Completed Paralyze Dog. [Last Updated On: June 26th, 2011] [Originally Added On: June 26th, 2011]
- 005 STEM CELLS - Bone Marrow Stem Cells (Balzitt).flv [Last Updated On: June 27th, 2011] [Originally Added On: June 27th, 2011]
- 006 Bone Marrow Stem Cells/Gene Therapy [Last Updated On: June 28th, 2011] [Originally Added On: June 28th, 2011]
- 007 Stem cells used for medical treatment [Last Updated On: June 30th, 2011] [Originally Added On: June 30th, 2011]
- 008 STEM CELLS FOR OTHER USES Interview with Sam Smith.wmv [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- 009 Stem Cells Reversing Endothelial Senescence [Last Updated On: July 2nd, 2011] [Originally Added On: July 2nd, 2011]
- 010 Bone Marrow Stem Cells [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- 011 Bone marrow transplantation HD, ENG subtitles [Last Updated On: July 5th, 2011] [Originally Added On: July 5th, 2011]
- 012 Adult Stem Cells May Target and Repair Heart Attack Damage [Last Updated On: July 6th, 2011] [Originally Added On: July 6th, 2011]
- 013 Bone Marrow Stem Cell Applications [Last Updated On: July 8th, 2011] [Originally Added On: July 8th, 2011]
- 014 Stem cells in bone marrow are being used to treat EB [Last Updated On: July 13th, 2011] [Originally Added On: July 13th, 2011]
- 015 STEM CELLS FOR MACULAR DEGENERATION Sam Smith's story.wmv [Last Updated On: July 14th, 2011] [Originally Added On: July 14th, 2011]
- 016 MS Cure - Progression [Last Updated On: July 14th, 2011] [Originally Added On: July 14th, 2011]
- 017 Blind Girl get's cure you need to see to believe" [Last Updated On: July 17th, 2011] [Originally Added On: July 17th, 2011]
- 018 From Surgical Repair to Stem Cell Repair: A Surgeon's Journey by Leonard Smith MD, FACS [Last Updated On: July 19th, 2011] [Originally Added On: July 19th, 2011]
- 019 Bone Marrow Stem Cell Donation [Last Updated On: July 19th, 2011] [Originally Added On: July 19th, 2011]
- 020 The potential of stem cells [Last Updated On: July 28th, 2011] [Originally Added On: July 28th, 2011]
- 021 LifeCell in Kalaignar Seithigal,Sun News [Last Updated On: July 31st, 2011] [Originally Added On: July 31st, 2011]
- 022 Spirulina DLA Naturals [Last Updated On: August 6th, 2011] [Originally Added On: August 6th, 2011]
- 023 Bill Lahti; stem cell nutrition stimulates wound repair for diabetic stroke victim [Last Updated On: August 6th, 2011] [Originally Added On: August 6th, 2011]
- 024 Christian Drapeau Talk About - Adult Stem Cells and StemEnhance./StemTech [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- 025 "Bone Marrow Stem Cells" Donald Kohn [Last Updated On: August 14th, 2011] [Originally Added On: August 14th, 2011]
- 026 Cancer Update: Autologus Stem Cell (Bone Marrow) Transplant [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 027 Bone Marrow / Stem Cell Transplant Recovery Fund [Last Updated On: September 6th, 2011] [Originally Added On: September 6th, 2011]
- 028 Bone Marrow/Stem Cell Transplantation: An Introduction, With Sonali Smith, MD [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- 029 Bone Marrow Stem Cell Transplant Live from Top US Hospital [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- 030 Adult Stem Cell Mobilization from Bone Marrow (Animation) [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- 031 MS Cure - Introduction to stem cell bone marrow transplant in Australia [Last Updated On: September 13th, 2011] [Originally Added On: September 13th, 2011]
- 032 Immune Modulation by Bone Marrow Mesenchymal Stem Cells [Last Updated On: September 14th, 2011] [Originally Added On: September 14th, 2011]
- 033 Bone Marrow/Stem Cell Transplant [Last Updated On: September 15th, 2011] [Originally Added On: September 15th, 2011]
- 034 Bone Marrow and Stem Cell Transplant Patients Share Their Stories [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 035 Stem Cell Transplant India,Bone Marrow Transplant India,Sickle Cell Anemia Treatment India [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 036 Bone Marrow Stem Cell Expansion by HOXB4 and p21 Knock Out [Last Updated On: September 21st, 2011] [Originally Added On: September 21st, 2011]
- 037 Multiple Sclerosis, Stem Cells, and Hope, Part 2 [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- 038 Becoming a Blood Stem Cell Donor [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 039 LittleBigPlanet 2 - Stem Cell Sackboy Quarter 4 Update (Bone Marrow Bugaloo) [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 040 Can Stem Cell Prolotherapy or Bone Marrow Prolotherapy help articular cartilage defects? [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- 041 Mesenchymal stem cells and marrow stromal cells [Last Updated On: October 1st, 2011] [Originally Added On: October 1st, 2011]
- 042 Bone Marrow Transplant and Stem Cell Transplant Treatment in India for International patients [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 043 Bone Marrow Stem Cell Aspiration and Re-Injection with PRP for Osteoarthritis by Dr Adelson [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 044 Selected Donor for Stem Cell, Bone Marrow [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 045 Stem Cell Injections - Bone Marrow Prolotherapy - treatment for arthritis [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 046 Nurses Discuss Special Bonds With Bone Marrow and Stem Cell Transplant Patients [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 047 Hagen's bone marrow collection part 1 [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 048 Samsparks after bone marrow collection for stem cell treatm [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 049 Chat w/ Dr. Maharaj, founder of S. FL. Bone Marrow/Stem Cell Transplant Institute [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 050 Bone Marrow - Stem Cell Prolotherapy [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 051 MS Cure - Hickman line Insertion for stem cell/bone marrow transplant [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 052 Bone Marrow Transplant Program Continues to Grow, Make a Difference [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 053 Stem cell transplant in children: what to expect | Dana-Farber Cancer Institute [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 054 LittleBigPlanet 2 - (WIP) Stem Cell Sackboy Bone Marrow Bugaloo [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 055 Calum's stem cell donation for Anthony Nolan [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 056 Stem Cell Treatment in New Jersey- Colon's story (Dr Damon Noto) [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 057 How to be an Anthony Nolan blood stem cell donor [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 058 Dr Steve talks about stem cells.mov [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 059 Stem Cells extracted from bone marrow [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- 060 Webinar 1, Stem cell therapy basics, what is available today? [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- 061 Mesenchymal stem cells and marrow stromal cells---2nd--- [Last Updated On: October 8th, 2011] [Originally Added On: October 8th, 2011]
- 062 Harvesting stem cells from horse bone marrow at UT [Last Updated On: October 12th, 2011] [Originally Added On: October 12th, 2011]
- 063 Bone Marrow Stem Cells - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- 064 Stem Cell Transplant Apheresis Method - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- 065 Mantak Chia: Sumup stem cell (Berlin,Germany 2009) Part I : Bone marrow activate Stem cell - Video [Last Updated On: October 16th, 2011] [Originally Added On: October 16th, 2011]
- 066 Stem Cell, Bone Marrow Transplants / Donations - Easy and life saving proceedure - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- 067 HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- 068 Sickle Cell Anemia: Stem Cell Gene Therapy - Donald Kohn - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- 069 Do you need a large number of stem cells injected for Bone Marrow Prolotherapy to work? - Video [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- 070 What are stem cells? - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 071 What is in situ Stem Cell Injection Therapy or Bone Marrow Prolotherapy? - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 072 Stem Cells Research at Hadassah - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 073 Blood or Bone Marrow Cells May Provide a Route to Healing Blood Vessels - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 074 Hematopoietic stem cell transplantation #2 - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- 075 Radiation - Sickle Cell Half Match Stem Cell Bone Marrow Transplant 2 - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- 076 Sickle Cell Stem Cell Bone Marrow Transplant 3 - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- 077 Macular degeneration - Stem Cell therapy (English subtitles) - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- 078 Where Do The Stem Cells Come From? Hollywood | Los Angeles - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- 079 Bone Marrow Stem Cell Injections - Video [Last Updated On: November 14th, 2011] [Originally Added On: November 14th, 2011]
- 080 Diabetes- Stem cell therapy (english) - Video [Last Updated On: December 2nd, 2011] [Originally Added On: December 2nd, 2011]
