Category Archives: Stem Cell Therapy

Nowadays, most people face teeth-related issues, expecting to retain their natural teeth or want functional teeth replacement with modern techniques. Modern techniques for missing tooth replacement include complete dentures, cast partial dentures, Implants, and prosthetic crowns. But these are not as equivalent to functional teeth and natural teeth. Recent research is ongoing on boosting tooth regeneration by inducing positive stress.

The study published online in the Journal of Dental Research by Dr. Waruna Dissanayaka, an Assistant Professor in Oral Biosciences, has overcome adaptive mechanisms in tooth stem cells preconditioning stress that boost tooth pulp tissue generation. This positive stress can have good changes in tooth stem cells by making them more resistant to disease and injury. So, in the future, this can help to improve implant cell survival and pulp tissue regeneration.

How positive stress can boost tooth regeneration:

When the tooth is injured or decayed, the vital tissue inside the tooth is exposed to harmful bacteria, which is susceptible to infection. If the tooth pulp is infected, the recent approach is to remove it and fill it with artificial material; when the pulp-less tooth is filled with inert material, the tooth dries, which makes the tooth brittle and more prone to crack and reinfection.

The only way is to replace the tooth with a prosthesis or extraction, but stem cell therapy can help in dental pulp regeneration, as per a recent study. Stem cells of human exfoliated deciduous teeth (SHED) preconditioned to a hypoxic condition by hypoxia-inducible factor 1 (HIF-1) stabilization via knockdown of prolyl hydroxylase domain-containing protein 2 (PHD2) using lentiviral short hairpin RNA. HIF-1 was inserted in Pura Matrix hydrogel, which was injected in the root canal of a human tooth fragment and implanted in immunodeficient mice. Then within 28 days, dental pulp-like tissue formation was seen with a higher level of vascularization, which helps enlist host blood vessels.

Dr. Waruna Disasanayaka and his team focus on developing the lost tooth pulp, which revitalizes the tooth and functions like a normal tooth. The tooth root canal is surrounded by hard dental tissue with less blood supply creating a harsh environment for cells of low oxygen and nutrients. So, the research team develops a preconditioning protocol that helps cells in low oxygen conditions to activate the protein.

Dr. Yuanyuan Han, a co-investigator of the team, pointed out: As this protein was reported to activate several key adaptive mechanisms, we wondered whether this phenomenon can be applied to improve cell survival following transplantation until a sufficient blood supply is achieved.

He also explained, In our study, we found that these cells activate a metabolic mechanism to produce energy under low oxygen conditions and scavenge harmful metabolites produced in stress conditions.

Dr. Dissanayaka says, Interestingly, we also found that preconditioned cells significantly enhanced the dental hard tissue formation within the regenerated pulp tissue. Former research has revealed that our cells possess number of adaptive mechanisms for stress, which are regulated by several key genes encoded in our DNA that are normally inactive.

If we can activate these genes, downstream expression of specific proteins can prime less vulnerable to injury, Dr. Dissanyaka said. He also said, Our aim is to find ways to take advantage of this capacity and use positive stress to help regenerate the dental tissues.

He aims to find new strategies to enhance the therapeutic potential of tooth stem cells.

This stem cell therapy helps to regenerate tooth tissue pulp which can help to retain natural tooth functioning. In the future, it will help to overcome teeth-related problems by avoiding the replacement of teeth by various means.

Journal Reference

Read more:
Positive stress can boost tooth regeneration - Tech Explorist

The University of Colorado Department of Ophthalmologys ocular stem cell and regeneration research program, CellSight, was awarded two prizes in the National Eye Institutes 3D Retinal Organoid Challenge (NEI 3D ROC).

The NEI, part of the National Institutes of Health, launched the three-phase challenge in 2017 to stimulate research using retina organoids. These organoids are similar to human retinas but aregrown in a lab from stem cells, enabling researchers to study eye diseases and treatments noninvasively.

CellSightDirectorValeria Canto-Soler, PhD, Doni Solich Family Chair in Ocular Stem Cell Research, led the team that won the NEI 3D ROCs disease modeling category, earning $500,000.Natalia Vergara, PhD, director ofCellSightsOcular Development and Translational Technologies Laboratory, led the research group that won the drug-screening category, earning $250,000.

According to a University of Colorado news release, Canto-Solers research group created a three-dimensional retinal model that recreates pathological features of age-related macular degeneration, with the ultimate goal of discovering new treatments for this blinding disease.

Its a privilege that we were able to participate in this endeavorand bring it to fruition, Canto-Soler, who is also an associate professor of ophthalmology at th CU School of Medicine, said in the universiys news release. This challenge is directed to what we all are trying to accomplish: move this field forward to be able to offer patients a therapy that helps them regain vision.

Vergara and her team continued their work in the third phase of the NEIs competition with their organoid model, having won phase II of the challenge in 2021.For phase III, they expanded their work to evaluate the effects of drug toxicities on the retina and developed a first-of-its-kind organoid model of Alzheimers disease retinopathy.

We are very excited because these awards are recognition of the work weve been doing for several years to bring these organoid technologies to the next level. We knew that there were certain challenges that needed to be overcome, mainly to provide a system that was robust enough that could be used for quantitative applications, Vergara explains. I think this project was successful because we were able to capitalize on a very diverse set of expertise to make something that will be really helpful for the scientific community and that will help us bring treatments to patients sooner.

This really shows how science has changed in the past several decades and how team science is the way to go now, she continues. When we work as a team, we can accomplish so much more than what any of us could accomplish on their own.

NEI Director Michael Chiang, MD, echoed the importance of team efforts behind the research.

All three of the teams exemplified this, Chiang says. I really love the spirit of all of you. The reason that were doing this is to cure blindness, eliminate vision loss, and improve quality of life.

The awards are a recognition ofCellSights contribution to the scientific community since its creation five years ago.

I want to congratulate Dr. Canto-Soler and Dr. Vergara on their well-deserved prizes in the NEIs 3D Retinal Organoid Challenge. I would also like to recognize the philanthropic supporters of theCellSightprogram, without whom we could not have assembled these great teams and fueled this pioneering work,Naresh Mandava, MD, chair of the CU Department of Ophthalmology and Sue Anschutz-Rodgers Endowed Chair in Retinal Diseases., said in the university news release. It is a testament to their tireless dedication to developing the science needed to find solutions for blinding retinal diseases. On behalf of my colleagues at the University of Colorado, we are so proud to see what we have already known as amazing science recognized in this fashion.

Vergara and Canto-Soler describe their research in videos, titled Improved Fluorescent Reporter Quantification-Based 3D Retinal Organoid Paradigms for Drug Screening" and 3D Human Model of AMD in a Dish. The projects are a collaboration with other research teams in the Department of Ophthalmology, theUniversity of Colorado Alzheimers and Cognition Center, NanoScope Technologies, LLC, and researchers at Miami University.

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University of Colorado's ocular stem cell and regenerative research program recognized - Ophthalmology Times

Photo/Laverock Therapeutics

Laverock Therapeutics Ltd has been founded to develop a gene silencing platform for the creation of programmable, allogeneic cell therapies.

Having recently completed a seed funding round, the U.K. company has opened dedicated labs in the Stevenage Bioscience Catalyst, employing six new team members on top of its senior management team.

Laverock Therapeutics started out in February as Skylark Therapeutics Ltd.

The companys mission is to utilize gene editing induced gene silencing (GEiGS) technology, and its associated computational platform, to engineer induced pluripotent stem cell (iPSC) derived cell therapies with improved efficacy, safety, and accessibility.

Laverock Therapeutics said earlier this year, it demonstrated its technology, exclusively licensed from Tropic Biosciences, would translate from plants to humans. The company has now created GEiGS engineered iPSCs, which it said further de-risks its platform technology and lays the foundation for its approach.

Experiments are under way to demonstrate cell type and condition specific programmability, generating data to support allogeneic programs in type 1 diabetes and solid tumor directed immune therapy.

CTO Tim Allsopp said: As the promise of iPSC-derived therapies continues to grow, so does our understanding of the limitations of existing approaches. Our novel technology has the potential to transform the sector via the creation of programmable, allogeneic cell therapies.

CEO David Venables added: We are thrilled to bring together such an experienced and knowledgeable team of scientific innovators and business leaders to drive forward Laverocks development. Id like to thank all our initial investors and supporters who have helped us reach this stage and look forward to bringing you news of further exciting developments as Laverock progresses.

Originally posted here:
Laverock Therapeutics created to develop programmable cell therapies - Labiotech.eu

James R. Martin/Shutterstock

A cell and gene therapy accelerator formed by Mayo Clinic, Hibiscus BioVentures and Innoforce is officially up and running, the partners announced Wednesday.

Mayflower BioVentures will identify and launch companies around technologies that address unmet patient needs.

Mayo Clinic hasaccumulated a portfolio of next-generation immune system modulators as well as numerous novel therapeutics in cell and gene therapy. Now Mayo is sharing those discoveries and research capabilities in hopes of reaching patients.

We have the first right to look at the technologies that Mayo considered to be high-value opportunities, Chris Jeffers, CEO of Hibiscus BioTechnology, told BioSpace. Thats an internal designation. And we have the first rights to create companies from those.

It gives Hibiscus the opportunity to incubate and accelerate the companies within Mayflower anywhere between one and two years. Eventually our goal is to graduate those companies to be self-sufficient, independent companies that can obtain their own funding once they leave the accelerator, Jeffers added.

Andrew Danielsen, chair of Mayo Clinic Ventures, told BioSpace that each company will be within Mayflower and owned by the investor syndicate proportionally.

Mayflower has been in the works for at least a year, Jeffers and COO Sia Anaganostou shared, adding that they have been working with Mayo on identifying and developing several companies, which they expect to announce in the coming months.

While unable to provide further details, Jeffers said the areas of focus are anticipated to range from various types of stem cell therapies and gene therapies covering a number of conditions. Some of those technologies are ancillary to cellular therapies, while some are for new pathways to try to escape from traditional immuno-oncology, he said.

Mayflower will be run by the Hibiscus management team.

This is a big push from the Mayo Clinic to really increase its commercialization in this space. Were really proud to be associated with such a fantastic institution with unparalleled clinical expertise, Jeffers said, adding that these factors are a real differentiator.

Danielsen spoke of transitioning research from bench to bedside.

We believe this collaboration can bridge the gap between industry and innovative cell and gene therapy research, enabling emerging startups to navigate the challenges of producing meaningful, novel therapeutics that transform health and medicine, he said in a statement.

Mayos Center for Regenerative Biotherapeutics focuses on advancing regenerative technologies from discovery into early phase clinical studies.

Hibiscus is a venture capital firm focused on building patient-focused companies around new technology and helping to develop those discoveries into commercial drugs and therapies. Hibiscus is comprised of Hibiscus Biotechnology, a venture studio that works to build companies from scratch, and Hibiscus Capital Management, a VC firm that invests in promising early-stage biotech companies.

Innoforce is a partnership-focused biopharma company targeting advanced therapy medicinal products (ATMPs) and biologics. It offers contract development and manufacturing services including GMP manufacturing of plasmid DNA, RNA, viral vector and cell products.

Any revenue generated by Mayflower will go toward Mayo Clinics patient care, education and research.

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Mayflower BioVentures to Announce New Cell & Gene Therapy Companies within Months - BioSpace

Nes-Ziona, Israel, Sept. 06, 2022 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd.(Nasdaq: ENLV, the Company), a clinical-stage macrophage reprogramming immunotherapy company targeting diseased macrophages in patients with sepsis and solid tumors, today announced that the U.S. Patent and Trademark Office issued a Notice of Allowance for patent application number 15/551,284. Once issued, the resulting patent will provide Enlivex with added intellectual property (IP) protection through at least 2036 with claims covering methods of using Allocetra to inhibit or reduce cytokine release syndrome in patients undergoing chimeric antigen receptor (CAR) T-cell therapy. The Company expects that this new patent will be issued in the United States by the end of the first quarter of 2023.

Oren Hershkovitz, PhD, CEO of Enlivex commented, We look forward to the anticipated issuance of this patent, which will broaden the robust IP portfolio protecting Allocetra and our various development programs. This IP portfolio is a key source of value for Enlivex, and we remain committed to its maintenance and continued expansion.

CAR T cells are T cells that have been genetically engineered to include a receptor that allows them to specifically target and destroy cancerous cells. While several CAR T cell treatments were recently approved by the FDA in several cancer indications, such treatments have been associated, in many patients, with a side effect named cytokine release syndrome, which describes a collection of potentially severe or life-threatening symptoms that stem from over-activation of immune pathways. Preclinical data indicate that Allocetra has the potential to prevent or reduce cytokine release syndrome associated with CAR T-cell therapies.

ABOUT ALLOCETRAAllocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

ABOUT ENLIVEX

Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra, a universal off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit http://www.enlivex.com.

Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as expects, plans, projects, will, may, anticipates, believes, should, would, could, intends, estimates, suggests, has the potential to and other words of similar meaning, including statements regarding expected cash balances, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRATMprograms. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affectEnlivexsbusiness and prospects, including the risks thatEnlivexmay not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATMproduct line could also be affected bya number ofother factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental,technologicaland other factors discussed inEnlivexsfilings with the Securities and Exchange Commission, including in the Companys most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law.

ENLIVEX CONTACT Shachar Shlosberger, CFO Enlivex Therapeutics, Ltd. shachar@enlivexpharm.com

INVESTOR RELATIONS CONTACTEric RibnerLifeSci Advisorseric@lifesciadvisors.com

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Enlivex Receives Notice of Allowance for U.S. Patent Application Covering the Use of Allocetra to Prevent Cytokine Release Syndrome in Patients...

After a long period of no change in the treatment paradigm for leukemias, updates in our understanding of disease pathology and molecular targeting have changed the outlook for many patients. Both acute and chronic types of leukemia have undergone evolutions in treatment approaches that have offered better survival outcomes and more tolerable regimens.

All of the changes in leukemia therapy, and in fact, in most hematologic [malignancies], have been occurring at a dramatic rate over the last 5 to 10 years, Jeffrey R. Schriber, MD, said in an interview with Targeted OncologyTM.

Studying the underlying molecular factors associated with different types of leukemia, including acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL), has enabled physicians to make more informed decisions on how aggressively to treat individuals with leukemia. This includes which targeted treatments can be employed and whether chemotherapy or hematopoietic stem cell transplant (HSCT) can be avoided.

Schriber, director of hematologic malignancies at Cancer Treatment Centers of America (CTCA) in Phoenix, Arizona, discussed the successes in the treatment landscape of leukemias and what challenges remain for oncologists.

Targeted OncologyTM: What are the most significant changes you have seen in the treatment of AML over the past 10 years?

SCHRIBER: Leukemia changed the most when we started to understand that there are molecular abnormalities present in some of these leukemias. We've known for a long time that FLT3 overexpression means a bad prognosis in AML and those patients don't do as well. We knew that allogeneic HSCT would work better for them. But what we didn't have is anything we could do about it. It was a little frustrating.

So investigators developed the FLT3 inhibitors. The first was midostaurin [Rydapt, Tauritmo]. There was a large randomized clinical trial [CALGB-10603; NCT00651261] where half of patients got it with standard chemotherapy, half of patients got [chemotherapy alone]. There was an impressive progression-free survival [PFS] and overall survival [OS] advantage to the group that received midostaurin.1 That was the first major change in leukemic therapy in over 20 years from an AML standpoint. Now, what you want to do immediately is test to see if the patient is FLT3 positive. If they are, midostaurin is added, or there are at least 2 other agents that target FLT3 as well.

But this recognition has led to other therapies. Now there is [ivosidenib; Tibsovo] for IDH1 mutations and [Enasidenib; Idhifa] for IDH2 mutations. We recognized that IDH1 and IDH2 carried the worst prognosis, and we now have inhibitors for both of those. The recognition that we have targeted therapies that can alter how we're treating the disease is probably the first huge thing that has happened [in this setting].

The average age of patients with AML is somewhere around 65 years. This type of therapy is pretty intense, and many of these patients, especially ones with FLT3-positive or harder diseases, would be looking at an allogeneic HSCT, and often they're very sick. Venetoclax [Venclexta] is an oral [inhibitor that] targets BCL-2. It has been used in combination with some of the agents that we commonly use that are well tolerated, like azacitidine [Vidaza], or decitabine [Dacogen]. Studies that are all 2 to 3 years old have shown even in these older patients who are not felt to be suitable for more aggressive therapy, that they are able to tolerate this and have an excellent complete remission rate.2,3 [Though it is oral], its still tough therapy. These patients drop [blood cell] counts and they can get sick. But that is a major advancement as well.

When I used to see patients with leukemia, I wanted to get them in, get their bone marrow [biopsy], make their diagnosis, know whether they had AML or ALL and [which] subtype, and I wanted to get them on therapy as soon as possible. That was always felt to be the mantra. But 2 years ago, there was a study done on the German Study Alliance LeukemiaAcute Myeloid Leukemia registry that showed that you don't have to do it right away, and if you wait and see if they're FLT3-, IDH1-, or IDH2-positive, you can tailor your therapy.4 That was another big thing that gave us a little sense of relief because we [learned] we don't have to [give treatment] right this second.

What improvements have been made in the treatment of ALL?

ALL is a disease that's much less common in adults. In adults, 80% of patients with leukemia have AML and maybe 20% or 30% have ALL. For children it's reversed. Children do very well with ALL, because [most patients] go on studies where they intensify the regimens. Those regimens can be very tough for some of the older adults to manage. But there's been a bit of a shift for adult patients under the age of 50. Its not the majority of adults with ALL, but in those patients, we've shifted towards a [pediatric-inspired] regimen. And if they can tolerate it, [patients receiving] those regimens seem to do a little bit better.5

In ALL, we usually see if patients are Philadelphia positive or Philadelphia negative. The Philadelphia chromosome is a translocation between chromosomes 9 and 22. It can cause CML, but it is also classic for ALL. They have a slightly different version of the genetic information that gets exchanged. Tyrosine kinase inhibitor [TKI] therapy blocks the tyrosine kinase that is responsible for this problem. For years, we've used those medicines to treat adults. But recently, there were data that as we get better TKIs, we may no longer have to give HSCT for all those patients.6 That became quite relevant in the COVID-19 era when we didn't want to take a patient through an allogeneic HSCT. One of the challenges we face is how do we know who [needs HSCT], because it is very effective, but its a tough thing to do. Are there patients we can cure? Traditionally, with Philadelphia-positive ALL, we always want to transplant. Recent data from The University of Texas MD Anderson Cancer Center group have shown with a better TKI, you may be able to avoid doing HSCT.7

We now use molecular testing [for minimal residual disease (MRD)] in both AML and ALL to determine whether there is still evidence of disease at very minute amounts. We've done this for years in CML.8 Being able to find minute amounts of disease is become very important because if we are able to get patients to these molecular responses with the regular therapies, they may not need an HSCT. It appears that some of these patients do just as well. The ability to [avoid] this very toxic therapy that is expensive and keeps patients in the hospital is a big advancement as well.

We now know in ALL that a patient may get into remission but they haven't achieved a molecular response. Molecular testing allows us to have a better 'camera' that gets a view of everything and says we may be able to avoid more intensive regimens for patients who are MRD negative. For patients who are MRD positive, there's a new medicine called blinatumomab [Blincyto], which is a bispecific T-cell engager. It takes CD19, a marker on ALL, and brings it together with the effector T cells. We can take patients who are molecularly positive and shift them to molecularly negative.9

Chimeric antigen receptor [CAR] T cells have changed what we do, particularly in young patients with ALL. I remember the first patient I had who I treated for relapsed leukemia [who received CAR T-cell therapy]. I had given her an allogeneic HSCT, and she did well for a period of time, but came back somewhere about 6 or 7 months after and that's usually a death sentence. At the time, there was a clinical trial of CAR T-cell therapy being done at The University of Texas MD Anderson Cancer Center. She did great for 2 years, and that was unheard of. The changes weve seen in ALL, particularly for CAR T, has been very gratifying. We can salvage patients that we couldn't have [before]. A lot of these patients are children because that's where the disease is more common.

The problem with CAR T cells is we're seeing failures now because we [are able to] follow up with patients. I think ALL is a little bit different, but in the lymphomas, [where we thought] this is going to cure patients, it's starting to come back, and we're seeing the same thing happening with multiple myeloma. The duration of this will be important to see whether we are going to continue [using] allogeneic HSCT. You can cure patients [with allogeneic HSCT], but it's tough therapy so we would like to have a replacement for if it's at all possible.

Have there been any recent changes in targeted therapy for CML?

In CML, we are building on [past efforts]. We have a brand-new medication for CML called asciminib [Scemblix], that targets different areas. In CML with the t(9;22) translocation, most TKIs target tyrosine kinases in one area, while this one targets the other. So in those rare patients that failed [other TKIs], this drug is more effective than some of the other drugs that we [compared it with] in a large randomized trial.10 So now we have a whole new target that we can go after. We usually think CML is an easy disease to deal with, and now we have something for when it [is harder to treat].

What are the most important new approaches to treating CLL?

CLL is the most common type of leukemia. Chronic leukemias usually go for many years, whereas the acute leukemias are the ones we need to treat right away. There are still many patients with CLL who we don't have to treat. Weve been able to identify biomarkers such as TP53, [which shows the disease will] be more aggressive. We look to see if patients have a mutation in the immunoglobulin gene, [which has] a favorable prognosis.

The biggest change has been the shift from chemotherapy, which we used to do 10 years ago, to immunotherapy. We have 2 different options. Venetoclax can be used with an antibody therapy and is very effective, but it can knock the [blood cell] counts down a little which makes patients sick. With COVID-19, we had to be careful about that.

The other set of agents are Bruton tyrosine kinase [BTK] inhibitors. BTKs are involved in how [malignant] cells are generated and proliferate. There are a variety of BTK inhibitors that have been effective, and they are now used up front in many patients. They were getting therapy with either ibrutinib [Imbruvica] or acalabrutinib [Calquence], and now there is a new one, zanubrutinib [Brukinsa].

[Due to these regimens], patients with CLL no longer get chemotherapy. What I think we will see soon is the combination of [venetoclax and BTK inhibitors] together, and we may even start talking about CLL as something that's going to stay away for a long period of time. Maybe we can talk about curing CLL down the road.

What are the most significant unmet needs in these types of leukemia?

The hardest thing is, what happens when the patients have failed therapies? That's where we spend a lot of our energy, and lot of the dollars in healthcare go towards that. We still need to be able to adjust quickly and [discover] how we can combine as many of these drugs as possible to get our best shot up front. That has been very hard because the way clinical trials work, for the most part, is you test 1 drug. What frustrates us sometimes is you can't do the study that you'd like to do. For instance, in CLL, we have [at least] 3 different drugs, and it would be nice to know that one is better than the other.

I think that's been tough because we can never move fast enough for [relapsed patients]. Weve made tremendous progress, but we still don't understand why some patients blow through regimens, and that is frustrating. The FLT3 [inhibitor] is standard; I think in time we will say, We used the IDH1 and IDH2 inhibitors; are there other therapies we can use? It's starting to happen, but it's not as well defined as I think it needs to be.

What is the most important piece of advice you would give to someone who is less familiar with recent developments in leukemia treatment?

My advice is to go to a center that [treats leukemia] a lot. One of the reasons I came to CTCA was to start a hematologic malignancies program, because like the changes I've talked about for leukemia, there are similar changes in lymphoma, in Hodgkin disease, and multiple myeloma. [Treatment for] these diseases continue to change on an ongoing basis, and it's hard to keep up.

If you're a general oncologist who mostly sees breast cancer, lung cancer, colon cancer, etc, its important to have someone who is an expert in immunological disorders. Go spend time at your center of excellence and learn the new therapies and the principles because the drugs will change. I would think about going to a center that does this. That's the way you learn. If I were a patient, I would want to go to a place where this is what they do primarily.

References:

1. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a flt3 mutation.N Engl J Med. 2017;377(5):454-464. doi:10.1056/NEJMoa1614359

2. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia.N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971

3. Maiti A, Qiao W, Sasaki K, et al. Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment-related mortality.Am J Hematol. 2021;96(3):282-291. doi:10.1002/ajh.26061

4. Rllig C, Kramer M, Schliemann C, et al. Does time from diagnosis to treatment affect the prognosis of patients with newly diagnosed acute myeloid leukemia?.Blood. 2020;136(7):823-830. doi:10.1182/blood.2019004583

5. Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019;133(14):1548-1559. doi:10.1182/blood-2018-10-881961

6. Short NJ, Kantarjian HM, Ravandi F, et al. Long-term safety and efficacy of hyper-CVAD plus ponatinib as frontline therapy for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2019;134(suppl 1):283. doi:10.1182/blood-2019-125146

7. Short NJ, Kantarjian HM, Konopleva M, et al. Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: Early results from a phase II study. J Clin Oncol. 2021;39(suppl_15):7001. doi: 10.1200/JCO.2021.39.15_suppl.7001

8. Branford S, Cross NC, Hochhaus A, et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia.Leukemia. 2006;20(11):1925-1930. doi:10.1038/sj.leu.2404388

9. Franquiz MJ, Short NJ. Blinatumomab for the treatment of adult b-cell acute lymphoblastic leukemia: toward a new era of targeted immunotherapy.Biologics. 2020;14:23-34. Published 2020 Feb 14. doi:10.2147/BTT.S202746

10. Ra D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs.Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984

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Leukemia Awareness Month: Improving Outcomes Over the Past Decade - Targeted Oncology