Stem Cell Clinic

FDA Approval Makes Pharming Drug First for Rare Inherited … – MedCity News

A rare immunodeficiency discovered just 10 years ago now has its first treatment. The FDA has approved a Pharming Group drug developed to treat activated phosphoinositide 3-kinase delta syndrome, or APDS, a disease that leads to low levels of white blood cells that fight pathogens and prevent infection.

The FDA said Friday that its approval of the drug, lenolisib, covers adults as well as children 12 and older who have APDS. Leiden, Netherlands-based Pharming will market its new twice-daily pill under the name Joenji.

APDS is caused by mutations to genes that encode PI3KD, a protein key for normal development and function of white blood cells. The disease particularly affects B and T cells, resulting in cells that improperly mature and malfunction. The disorder makes patients more susceptible to recurrent infections in the sinuses, ears, and respiratory tract. It may also lead to enlarged lymph nodes, tonsils, spleen, and other organs, which can obstruct the airways and gastrointestinal tract. Furthermore, this protein deficiency also makes patients more prone to developing blood cancers.

The overlapping symptoms of primary immunodeficiencies lead to APDS frequently being misdiagnosed. The disease was first characterized in 2013 and can now be diagnosed with genetic testing. According to Pharming, APDS affects an estimated 1 million to 2 million people worldwide. Treatment has consisted mainly of symptom management: prophylactic antibiotics, immunoglobulin replacement, and immunosuppression. If lymphomas develop, chemotherapy and stem cell transplants are treatment options, but these treatments introduce new complication risks.

Joenji is a small molecule designed to block the PI3K-delta protein, an approach intended to inhibit signaling pathways that lead to dysregulation of B cells and T cells. FDA approval of the drug is based on a placebo-controlled Phase 2/3 study that enrolled 31 adults and children 12 and older with a mutation PI3K-delta mutation. The FDA said results showed that by day 85 of the study, patients in the Joenja group showed a reduction in the size of their lymph nodes and normalization of their levels immune cells, as measured by calculating the percentage of nave B cells out of total B cells, indicating improvement.

Pharming already has one FDA-approved product, the hereditary angioedema drug Ruconest. In 2021, that drug accounted for 198.8 million in revenue, down 9% from the prior year. Pharming licensed Joenji from Novartis in 2019, paying $20 million up front. The two companies partnered on Phase 2/3 testing. An additional $200 million is tied to the achievement of regulatory and sales milestones. Novartis is also entitled to receive royalties from Pharmings sales of the new drug.

FDA approval of Joenja comes with a priority review voucher (PRV) that entitles Pharming to receive speedy review of a future rare disease drug. Pharming said that according to the terms of the companys license agreement with Novartis, the pharmaceutical giant has the right to purchase this voucher for a small minority share of the value of the PRV.

Pharming has scheduled a Monday, 8 a.m. Eastern time conference call to discuss Joenjas approval.

Image by Flickr user NIAID via a Creative Commons license

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Delivery Matters: In Early Studies, DPX Technology Allows Vaccines … – AJMC.com Managed Markets Network

As cancer treatments have evolved, scientists have worked to improve 2 things: making the responses to therapy last longer, and limiting how much collateral damage the therapy does as it attacks the tumor. The arrival of immunotherapy has been monumental: across many types of cancers, response rates to immunotherapy are higher, deeper, and more durable than with chemotherapy.1 When responses occur, adverse events in immunotherapy are different but manageable, and quality of life is improved.

Still, not every patient benefits. Not everyone responds, and despite the advances of the last decade, some cancers have high rates of recurrence; ovarian cancer, for example, has a rate of 85%.2 For all the wonders of chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL), about 40% of patients relapse.3 Thus, the quest continues for treatments that last longer with fewer adverse events (AEs); in the United States, this may also allow the patient to keep a job that provides health coverage.

It's these highly refractory patients that the biotech IMV is enrolling in trials, so it can examine its novel delivery platform for immunotherapy, one designed to teach the bodys immune systemincluding the innate immune systemto deliver a sustained response against cancer. Based on promising results, including the SPiReL study in DLBCL,4-5 IMV has moved into phase 2b trials in both DLBCL and ovarian cancer with its lead therapeutic candidate, maveropepimut-S (MVP-S), which is a cancer vaccine composed of survivin epitopes that uses the companys proprietary delivery system, called DPX.

The VITALIZE Phase 2b trial (NCT04920617) is a randomized, parallel group 2-stage study that will evaluate MVP-S with pembrolizumab (Keytruda) in patients who have received at least 2 lines of systemic therapy and are ineligible for or have failed autologous stem cell transplant (ASCT) or CAR T therapy. Positive preliminary data from VITALIZE were shared February 13, 2023, at the IO 360 meeting in New York, New York.6 Data shared showed:

A phase 2b, single-arm study called AVALON (NCT05243524) involves MVP-S with intermittent low-dose cyclophosphamide in patients with platinum-resistant ovarian cancer.7 The MVP-S agent with pembrolizumab combination is also being studied in bladder cancer.8

Vaccines That Persist in Fighting Cancer

In an interview with Evidence-Based Oncology, (EBO) prior to the IO 360 presentation, Jeremy Graff, PhD, explained the science behind the DPX platform. Most people are familiar with prophylactic vaccinessuch as those that prevent polio, measles, or COVID-19which he said are used to prevent a disease from taking root. Therapeutic vaccines, Graff said, must accomplish a different task. Not only must they create a response that works immediately against the disease, but they must also generate a response that is persistent, meaning it keeps working against the disease despite the microenvironment that the cancer or chronic illness has setup to insulate against an attack.

With a prophylactic vaccine, When we educate our response to poliovirus, there's nothing that pushes back against that response, Graff explained. By contrast, when we educate a response to a cancer protein, the cancer itself is pushing back against that response all the time.

Cancer vaccines have failed in the past, he said, because they have not generated this persistent response. Prior efforts have tried to deploy a prophylactic strategy, with the hope that would become therapeutically useful. Instead, Graff said, the immune response is temporarily ignited but ultimately shuts down, in many cases by the cancer itself.

DPX takes an entirely different approach by packaging its vaccine, or other cancer-fighting cargo, in a way that ignites the innate immune system, so that it digests the key antigens that we want the immune system to pay attention to, he said. Instead of flooding the patient with poorly targeted chemotherapy or more precise immunotherapy, Graff explained, the DPX platform works to hand deliver antigens with the right signals to the T cells and B cells of the adaptive immune system, so they are trained in waves to fight cancer.

Carrying the Cargo in Oil

Our formulation is very different, Graff said. We resuspend our immune-educating cargo, whether theyre antigens in the form of proteins, or peptides, or RNAs, in an oil. And then we inject that oil-based solution into the subcutaneous space.

The solution stays put until the antigen-presenting cells of the innate immune system arrive to carry the injection to the lymph nodes, where they can work against cancer. Prior systems just let vaccines fall part in tissue, Graff explained.

It takes time to carry the injection to the lymph nodes, and with the DPX system investigators allow 60 days for the vaccine to be carried through the immune system; then another injection starts the process again. EBO asked Graff: does each patients innate immune system deliver the vaccine on the bodys own timetablecreating, essentially, a new type of personalized medicine?

You can kind of think of it that way, Graff responded. When the antigen-presenting cells pick up on the vaccine, they do so along with whatever bacteria, fungi, or viruses an individual already brings to the system. Whatever the immune system looks like, the antigens still train the T and B cells.

Can the DPX technology, with its oil-based solution, work with other cancer-fighting agents besides what is currently under study? Graff says yes. We think we can take all different types of cargo, he said. The lead product is licensed from Merck KGaA (Germany); it had been tested with a standard emulsion, but no clinical benefit was seen. Used with DPX, Graff said, We now see a much more robust immune responseits much more persistent. It leads to clinical benefit and has done so in multiple cancer types.

Could this mean that molecules that showed promise in mouse models but didnt pan out in early human trials could see new life with DPX technology?

Absolutely, Graff says enthusiastically. We can package whole viruses, we can package large proteins, multiple proteins, antigens, RNAswe can do all sorts of stuff with our formulation, he said.

We would say in a short way, delivery matters, Graff said. If you don't deliver antigens to the immune system correctly, you can't expect the immune system to react correctly.

Will the Markets Respond?

Despite the previous findings and well-received preliminary VITALIZE data presented at IO 360, IMV finds itself in a quandary. In a March 16, 2023, conference call to discuss annual fiscal year-end financials, CEO Andrew Hall was at a loss to explain the recent sell-off of IMV shares. That fact that we have seen the same number of complete responses in the first handful of patients as we had seen for the whole SPiReL trial, and those complete responses have been confirmed by at least 2 scansone at 70 and one at 140 daysis, to say the least, encouraging, he said during the call.9

The current financial landscape for small biotechs is challenging, Hall said. It's for this reason, we've engaged our long-time partner, Stonegate, to help us explore strategic options in this difficult market, he said.

Hall also wanted investors to understand just who the patients are that IMV is reaching. I want to highlight one of those complete responses in VITALIZE that was presented at the recent IO 360 meeting in New York. This patient is young man, 24 years old. His disease had progressed through standard rituximab-based therapy, then stem cell transplant, and, more recently, through CAR T therapy.

He was running out of options, Hall continued. He enrolled in the VITALIZE trial last fall. On his first scan 70 days later, his disease was gone. On his second scan, he is a complete confirmed responder. For the first time since diagnosis, this patient is back at the gym and doing things a 24-year-old should be doing.

Graff explained why 2 patients could not stay on study. The trial criteria call for patients to have a life expectancy of at least 90 days; some patients simply are not making it through the screening phase.

In its March 16, 2023, statement, IMV said it will complete stage 1 enrollment in VITALIZE (30 patients) during the second quarter of 2023; it will complete stage 1 enrollment of AVALON in the third quarter of 2023 (approximately 40 patients), and will present preliminary phase 1 data involving MVP-S and the DPX platform in non-muscle invasive bladder cancer in third quarter of 2023.10

References

1. Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17(8):807-821. doi:10.1038/s41423-020-0488-6

2. Blevins Primeau AS. Cancer recurrence statistics. Cancer Ther Adv. November 30, 2018. Accessed March 21, 2018. http://bit.ly/3FGfwMj

3. Larson RC, Maus MV. Recent advances and discoveries in the mechanism and functions of CAR T cells. Nat Rev Cancer. 2021;21(3): 145161. doi:10.1038/s41568-020-00323-z

4. Berinstein NL, Bence-Buckler I, Forward NA, et al. Clinical effectiveness of combination immunotherapy DPX-Survivac, low dose cyclophosphamide, and pembrolizumab in recurrent/refractory DLBCL: the SPiReL study. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 4-8, 2020; virtual. Abstract 2114. http://bit.ly/3lwM9Fb

5. IMVs survivin-targeted T cell therapy shows durable clinical benefits in phase 2 study in patients with hard-to-treat advanced recurrent ovarian cancer. News release. IMV Inc. December 3, 2020. Accessed March 21, 2023.https://bwnews.pr/3lDxzWu

6. IMV Inc. presents positive initial results from the MVP-2 phase 2b VITALIZE trial. News release. IMV Inc. February 13, 2023. Accessed March 21, 2023. http://bit.ly/3FFCW4e

7. IMV Inc. announces update and planned 2023 milestones to advance clinical development of its lead therapeutic, MVP-S. News release. January 8, 2023. http://bit.ly/3JY8ftN

8. Our clinical pipeline. IMV Inc. Accessed March 21, 2023. https://www.imv-inc.com/pipeline

9. Fourth quarter and fiscal year 2022 results webcast. IMV Inc. website March 16, 2023. Accessed March 17, 2023. http://bit.ly/3JrK7hC

10. IMV Inc. announces strategic update as well as fourth quarter and full year 2022 and financial and operational results. News release. IMV Inc. March 16, 2023. Accessed March 17, 2023. http://bit.ly/3ltNSv3

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Delivery Matters: In Early Studies, DPX Technology Allows Vaccines ... - AJMC.com Managed Markets Network

When to Use Second-Line CAR T-cell Therapy for Relapsed … – Targeted Oncology

Gilles Salles, MD

Chief of Lymphoma Service

Steven A. Greenberg Chair

Memorial Sloan Kettering Cancer Center

New York, NY

Targeted OncologyTM: How do the National Comprehensive Cancer Network (NCCN) guidelines recommend treating patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) based on the outcomes of first-line therapy?

SALLES: [Looking at] the NCCN guidelines, for patients with the intention to proceed to autologous stem cell transplant (ASCT), second-line therapy is divided by complete responders with ASCT, partial responders [who] usually go to CAR [chimeric antigen receptor] T-cell therapy, and those with progressive disease who will go to salvage therapy or CAR T-cell therapy.1 Patients with relapsed disease within 12 months, or primary refractory disease, should envision CAR T-cell therapy and the nontransplant candidates will go to a couple of suggested regimens.

If we go back to those patients with the intention to treat with CAR T-cell therapy, we have to think of patients a little differently from [the way one is] used to thinking. Were used to seeing patients [in terms of being] eligible or ineligible for ASCT. [Now,] for these [patients relapse] early, [we have to ask if they] are eligible for CAR T-cell therapy and decide who is more [optimal] for CAR T-cell therapy. Thats probably a good discussion [to have]. In this case, we have both axicabtagene ciloleucel [axi-cel; Yescarta] and lisocabtagene maraleucel [liso-cel; Breyanzi] available for patients.

At what point can CAR T-cell therapy be used for patients with relapsed/refractory DLBCL?

Regarding their [FDA] approvals, axi-cel was approved for patients who are refractory to first-line therapy or relapse within 12 months of first-line chemoimmunotherapy.2 The way we all interpret that is 12 months from the end [of first-line therapy], though initially some of the trials [did otherwise]. Liso-cel has a slightly different label: refractory disease or first-line relapse within 12 months of first-line therapy, then there is an addendum which is based on the study: refractory disease to first-line chemoimmunotherapy or relapsed after first-line chemoimmunotherapy and not eligible for ASCT.3

For axi-cel, the ZUMA-7 trial [NCT03391466] was taking patients from the time of relapse, [performing] apheresis on the patient, bridging them with steroids but not with chemotherapy, which may make [a difference].

What were the efficacy outcomes of the phase 3 trials investigating second-line CAR T-cell therapy?

[There were] 3 trials [of CAR T-cell therapy for DLBCL], ZUMA-7, BELINDA [NCT03570892], and TRANSFORM [NCT03575351].4-6 Patients were in the range of 55 to 60 years of age [on these trials]. They had the same criteria of eligibility; all these patients [relapsed after] less than 12 months. In ZUMA-7, the only bridging therapy was steroids whereas BELINDA, the one with tisagenlecleucel [tisa-cel; Kymriah] and TRANSFORM with liso-cel were offering the possibility of 2 or 3 cycles of chemotherapy as bridging therapy.

Two-thirds to three-quarter of patients were refractory, [and approximately] 25% were relapsed [across these studies]. The median follow-up was quite different; [approximately] 2 years for ZUMA-7, 10 months for BELINDA, and 6 months at the time of publication of TRANSFORM. The complete response [CR] rate to CAR T-cell therapy in ZUMA-7 was 65%, and the CR rate with ASCT was 32%.4 With BELINDA there were no difference between the 2 groups, a CR of 28% [in each arm],5 and with TRANSFORM [the liso-cel had a] 66% CR rate which is identical to ZUMA-7 and 39% with ASCT.6

Two of the studies were positive, the third one is negative. If you want to know why is the third one was negative, is it a question of product, is it a question of trial design, is it a question of delays in manufacturing the product? I think there were many explanations raised. I personally think there was not one single explanation; it was a mixture of different explanations. Tisa-cel [is an effective] primary CAR T-cell therapy for children with acute lymphoblastic leukemia, so its a good [therapy], but in this DLBCL setting it may be inferior, and there are some data from a registry study coming from [France] suggesting that it is inferior to axi-cel.7

[For ZUMA-7, the PFS [progression-free survival] rate at 24 months was 46% for axi-cel versus 27% for ASCT.4 In BELINDA [PFS data were] not provided, [so PFS in both arms were] not reached,5 and [for TRANSFORM] we have a 12-month PFS rate of 50% vs 33%, so a highly significant difference for 2 [of these trials].6 So its a significant change for early relapse, and potentially for later [relapse].

REFERENCES

1. NCCN. Clinical practice guidelines in oncology. B-cell lymphomas, version 2.2023. Accessed March 23, 2023. https://bit.ly/3TEXEqA

2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed March 23, 2023. https://bit.ly/3ngfNPF

3. FDA approves lisocabtagene maraleucel for second-line treatment of large B-cell lymphoma. News release. FDA. June 24, 2022. Accessed March 23, 2023. https://bit.ly/3TBFcPE

4. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

5. Bishop MR, Dickinson M, Purtill D, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022;386(7):629-639. doi:10.1056/NEJMoa2116596

6. Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6

7. Bachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma.Nat Med. 2022;28(10):2145-2154. doi:10.1038/s41591-022-01969-y

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When to Use Second-Line CAR T-cell Therapy for Relapsed ... - Targeted Oncology

Updates on Recent Advances and Treatments for Hematologic … – Targeted Oncology

With the increasing frequency of almost all diseases covered by hematologic malignancies, many questions and new ideas are constantly being answered and addressed for patients and physicians. As a result, a 2-day symposium, the Summit of the Americas on Immunotherapies for Hematologic Malignancies, was created to provide an overview of the most recent advances in hematologic oncology.

During the meeting, 25 experts joined director of the Summit of the Americas on Immunotherapies for Hematologic Malignancies, Guenther Koehne, MD, PhD, for the opportunity to discuss and learn about some of the new developments in the treatment of patients with leukemia, lymphoma, multiple myeloma, and stem cell transplantation and more.

Presentations highlighted at this year's meeting included discussions on several novel immunotherapies, new combinations, and even updates on the evolving field of molecular-based therapies.

The reason why we have this summit is to update physicians and faculty members on the new developments in the field. Immunotherapies are developing relatively fast, and we are all excited about the implementation of these immunotherapeutic approaches, Koehne, deputy director and chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida, said in an interview with Targeted OncologyTM.

In the interview, Koehne provided an overview of The Summit of Americas on Immunotherapies for Hematologic Malignancies and some of the recent and exciting advances being seen in the hematology space.

Targeted Oncology: Can you explain the purpose of The Summit of Americas on Immunotherapies for Hematologic Malignancies?

Koehne: The title of the conference gives away a little bit. It's a global summit on immunotherapies for hematologic malignancies. The reason why we have this summit is to update physicians and faculty members on the new developments in the field. Immunotherapies are developing relatively fast, and we are all excited about the implementation of these immunotherapeutic approaches.

In all diseases that are covered by hematologic malignancies, that is acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, multiple myeloma, each of these diseases have specific drugs or combinations of drugs with an antibody that can specifically target tumor cells without targeting healthy cells, which wouldn't be the case with chemotherapy and chemotherapy combinations that we've been given before. Now, with the rapid development, there are so many questions that we've tried to answer or at least address. We cannot answer all of them because of the rapidity of the development. But for example, is 1 immunotherapeutic drug enough to get the patient into long lasting remission? Or should we combine them, or should we sequence them? Then there's still the follow-up question of when to provide the patient or send them for a stem cell transplantation, which would be an autologous stem cell transplantation for multiple myeloma or donor-derived allogeneic stem cell transplantation for patients with leukemia. As of now, that is still the only curative therapy that we have.

We also know that the patients should be in a complete remission. Particularly now we have very sensitive tests that we summarize as minimal residual disease, MRD, testing. We know that patients that are MRD-positive before an allogeneic stem cell transplant for acute myeloid leukemia, do as well as those that are MRD-negative. Now with these new approaches and targeted therapies, we are trying to get them into a complete remission before sending them to the allogeneic stem cell transplantation. All these topics are addressed [at this meeting] and they are important to answer.

What ongoing research has recently caught your eye in the hematology field?

I'm the principal investigator for a lot of new clinical trials specifically addressing FLT3-mutated acute myeloid leukemia, TP53-mutated myeloid leukemia, and I have a lot of trials in the workup for multiple myeloma. I'm leading 1 exciting clinical trial now that for the first time utilizes the CRISPR technology, which is molecular silencing and therefore down regulating the CD33 expression on hematopoietic stem cells. With that, we can now transplant patients with acute myeloid leukemia with CD33-negative hematopoietic stem cells. One may ask, why is that important? Because CD33 is also expressed on leukemia cells. The reason why we cannot target specifically acute myeloid leukemia with CAR T cells, or with any specific CD33 targeting antibodies, is that you would also target the healthy hematopoietic stem cell at the same time.

To prevent this, we can downregulate and transplant the patient with CD33-negative stem cells, and everything that is left after transplantation expressing CD33 is then the leukemia cells. With that, we have a specific targeting approach for this patient population as well. We have successfully transplanted 3 patients with these CD33-negative stem cells, and we can prove at this point that it's safe. We can follow up with immunotherapies for these patient populations, and that is clearly exciting and accompanied new levels of immunotherapeutic approaches in our view.

Wonderful, and are there any other future advances in the hematologic malignancy field that you're excited about?

Multiple myeloma has a lot of interesting developments right now with the so-called bispecific antibody treatments of the CAR T-cell treatments, specifically, in this case, targeting the B-cell maturation antigen or BCMA. That will lead to long-term maintenance of remissions.

I believe that will also add this topic of the discussion here at this meeting now, because with the CAR T cells or bispecific antibodies that specifically get the patients into a remission again, what is the role of autologous stem cell transplantation? In this scenario, do we still need autologous transplant or what would be the best timing for autologous stem cell transplantation in patients with multiple myeloma? It is an ongoing discussion. I personally believe that autologous stem cell transplantation still has a good and important role in maintaining a long-lasting relationship with these patients, with the CAR T cells that we have, or with the bispecific antibodies that we have and we can bring patients back into remission.

These remissions have a limited duration, so that indicates to me that 1, achievement of the complete remission patient should then be consolidated with autologous stem cell transplantation, which leads to more transplants than we had before because you don't transplant patients if they don't necessarily have a good remission.

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Heart tissue heads to space for research on aging and impact of … – Cardiovascular Business

Other NASA experiments look at long spaceflight impact on the heart

Many recent medical studies on the space station use tissue chips like the Hopkins experiment. In other cases, tissues made from cells engineered to reproduce specific characteristics, and even organoid 3D structures made up of all the different types of cells in a particular organ including the heart, have been studied. These stand-ins for actual hearts enable new types of research and drug testing.

NASA said an investigation completed in 2018, Cardiac Myocytes, first showed that microgravity helps specially programmed stem cells move toward becoming new heart muscle cells. The experiment delivered frozen stem cells to the space station where crew members thawed and cultured them before returning the samples to Earth for analysis and comparison with control batches.

Subsequent research took advantage of microgravitys effect on cell behavior and growth to create tools for further research, model disease and test potential treatments for heart damage. TheMVP Cell-03study examined the production of heart cells from human-induced pluripotent stem cells (hiPSCs) in microgravity. Pluripotent cells are cells that have started to differentiate, making them more specialized than a stem cell, but that retain the ability to become multiple cell types. MVP Cell-03 showed that microgravity increased production of cardiomyocytes from hiPSCs. This increased production could make it possible to use cultured cells to help treat spaceflight-induced cardiac abnormalities and to replenish heart cells damaged or lost due to disease on Earth. Damaged human cardiac tissues cannot repair themselves, and loss of heart cells contributes to eventual heart failure.

If we want to use these cells for clinical applications, we need to be able to generate a lot of them in an efficient way, said MVP Cell-03 Principal Investigator Chunhui Xu, PhD, of the Emory University School of Medicine and Children's Healthcare of Atlanta in a statement. Heart replacement therapy, for example, requires at least a billion cardiomyocytes for just one patient.

The research also showed that space-grown cells have appropriate structure and function. That means they can be used to test drug safety. Now we can test in a dish whether a drug causes adverse effects, she said. This research can even use a persons own blood cells to produce hiPCS cells and, in turn, heart cells that can be used to determine how the individual might react to a specific drug.

The next step is to look at the quality of cells produced with the Project Eagle study, scheduled to launch later in 2023.

"What we have in our dish now is immature cells. They dont behave the way real heart cells behave, but are more similar to embryonic heart cells," Xu explained. "Transplanting those could be an increased risk for the patient. Project Eagle looks at whether microgravity might be an effective approach to push the cells to more mature stages.

Xus lab also tested using cryopreservation, a process of storing cells at -80C (-112F), as an alternative to delivering live cell cultures to the space station. The team determined that cryopreservation does not appear to negatively affect the cells and even protects them from the effects of excess gravity experienced during launch. This technique makes it easier to plan future research since experiments do not have to start as soon as the cells reach the station.

The Cardinal Heart study took place on the space station in 2021, which used engineered heart tissues to confirm that microgravity exposure causes significant changes in heart cell function and gene expression that could lead to damage. The study was a collaboration between Joseph Wu, MD, PhD, with Stanford University, andBeth Pruitt, PhD, with the University of California Santa Barbara.

The Cardinal Heart 2.0 study, which also was part of the payload in the March 14 resupply mission launch, takes this research to the next step. It uses a beating heart organoid that contains stem cell-derived cardiomyocytes, endothelial cells and cardiac fibroblasts, which form supportive connective tissue, to test whether certain drugs can reduce or prevent microgravity-induced changes. Using tissue chips to test new drugs could help reduce the need for the animal studies required before clinical trials in humans, potentially shortening the time between discovery of a drug candidate and its clinical use.

Funding for Cardinal Heart and the Engineered Heart Tissues research was provided by the National Institutes of Health (NIH).

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Heart tissue heads to space for research on aging and impact of ... - Cardiovascular Business

Improving Multiple Myeloma Diagnosis with Advanced Treatments – News18

Multiple myeloma is a type of blood cancer that affects the plasma cells, which are responsible for producing antibodies in the body. Being one of the most common blood cancer, it requires timely diagnosis and treatment. Over the years, there have been many advances in the diagnosis and treatment of multiple myeloma, leading to better outcomes for patients.

Plasma cells, a subset of white blood cells that make antibodies, are the target of the malignancy known as multiple myeloma. Early diagnosis and treatment of multiple myeloma are crucial for improving outcomes and enhancing chances of survival," says Dr S Jayanthi, Senior Pediatric Oncologist, Kamineni Hospitals, Hyderabad.

The latest treatment approaches to enhance the chances of diagnosing multiple myeloma are offering promising new treatments. Many multiple myeloma patients receive chemotherapy in order to reduce or eliminate their cancer cells. In some cases, chemotherapy may also lead to cancer remission. However, long term cancer control can often be difficult to achieve with this approach alone. Allogeneic bone marrow transplantation is a new treatment option that has shown promise for many multiple myeloma patients and is considered a more aggressive approach than just chemotherapy alone," adds Dr Jayanthi.

Early diagnosis and treatment of multiple myeloma are essential for improving outcomes and enhancing chances of survival. The latest treatment approaches, such as advanced imaging tests, biopsy, genetic testing, targeted therapies, and immunotherapy, can help to diagnose multiple myeloma and provide personalized treatment plans for better outcomes.

Advancements in imaging technology, such as PET-CT and MRI scans have allowed for more precise assessment and can detect myeloma lesions earlier than traditional X-rays, which can be critical for early diagnosis and effective treatment. Another newer advance in the treatment of multiple myeloma is the use of precision medicine. Precision medicine involves using genetic testing to identify the specific genetic mutations that are driving the growth of myeloma cells. Once these mutations are identified, targeted therapies can be used to block their effects and stop cancer from growing. This approach can lead to more personalized and effective treatment for each individual patient," says Dr Ashish Dixit, Consultant, Haematology, Haemato Oncology & Bone Marrow Transplantation, Manipal Hospital Old Airport Road.

Targeted therapies are newer treatment options for multiple myeloma. These drugs are designed to target specific proteins or pathways that are essential for the growth and survival of myeloma cells. An example of targeted therapy for multiple myeloma can be proteasome inhibitors, such as bortezomib. These drugs block the breakdown of proteins in myeloma cells, leading to their death.

Another newer treatment option for multiple myeloma is monoclonal antibodies, which are designed to target specific proteins on the surface of myeloma cells. Daratumumab is an example of a monoclonal antibody used in treating multiple myeloma. This drug helps the immune system recognize and attack myeloma cells more effectively," adds Dr Dixit.

Stem cell transplantation is one of the standard treatments for multiple myeloma. Stem cell transplantation involves collecting healthy stem cells from the patient or a donor, and then administering high doses of chemotherapy to kill cancer cells. The healthy stem cells are then infused back into the patients body, helping to restore the immune system and blood cell production.

Targeted Immunotherapy is a treatment option that uses the bodys immune system to fight cancer cells. One type of immunotherapy used in multiple myeloma is called CAR T-cell therapy. This treatment involves modifying the patients own T-cells in a laboratory so that they can recognize and destroy myeloma cells more effectively," opines Dr Dixit.

These newer advances in the diagnosis and treatment of multiple myeloma offer hope for patients with this disease. With continued research and development, we may see even more effective treatments in the future. It is important for patients with multiple myeloma to work closely with their doctors to determine the best course of treatment for their individual needs.

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Improving Multiple Myeloma Diagnosis with Advanced Treatments - News18

Promise of targeted drug for rare leukemias comes with Karnataka connection – Deccan Herald

Targeted drugs have reinforced the treatment of cancer even as researchers fast-track studies on the resistance cancer cells develop against these precision therapies.

A new study by researchers in Finland and Denmark has identified a targeted drug that could counter resistance in two rare subtypes of acute myeloid leukemia (AML) the cancer of the blood and bone marrow that have limited treatment options. The findings from the study conducted by the University of Helsinki, HUS Comprehensive Cancer Centre, and the University of Copenhagen are expected to improve the prognosis of erythroid and megakaryoblastic leukemias and make the selection of targeted drugs more precise. Studies estimate that the two subtypes account for less than 5 per centof all AML cases.

Also Read |Cancer, high BP, diabetes have treatment in Ayurveda but not in allopathy: Ramdev

The study showed that cells grouped under the two subtypes depended on BCL-XL for their survival. BCL-XL is a protein that prevents apoptosis or programmed cell death. The researchers tested 528 drugs for their efficacy on 21 human leukemic cell lines and AML patients and found BCL-XL protein inhibitors to be highly effective in killing the cancer cells.

Given the poor prognosis associated with erythroid and megakaryoblastic leukemias and the limited targeted therapy options, we propose BCL-XL as a viable target for further exploration in the treatment of these leukemia subtypes, the researchers said. The study has appeared in Blood, the peer-reviewed journal published by The American Society of Hematology.

An article on the study published on the University of Helsinkis website quoted Heikki Kuusanmaki, postdoctoral researcher, as saying that the findings validated patients with the two forms of leukemia as a promising group to test BCL-XL inhibitors efficacy in clinical use.

The Karnataka connection

Komal Kumar Javarappa, a translational scientist who worked as part of the research team at the University of Helsinki, told DH that the study analysed diverse leukemia subtypes with different genetic mutations to arrive at a potentially effective therapy. A native of Arakalgud in Karnatakas Hassan district, Komal is a specialist in flow cytometry a laser-based technique that is used to detect and analyse the properties of cells and other particles with research experience in immunology and hematological malignancies.

Komal, now doing research at the National University of Singapore, received his Masters degree and doctorate from the University of Mysore, in 2012. His postdoctoral research included work on stem cells and leukemia, at institutions in Sweden, Finland, and Denmark.

The study involved tracking of cell signaling pathways (which also indicates the characteristic changes in cancer cells). With a larger cohort, we can track the impact of the drug on a more diverse dataset, he said.

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Promise of targeted drug for rare leukemias comes with Karnataka connection - Deccan Herald

Complete Bone Response Observed in Trial of AB8939 for AML – Targeted Oncology

Treatment with AB8939, a microtubule destabilizer, resulted in a complete bone response in a patient with relapsed and refractory acute myeloid leukemia (AML) in a phase 1/2 study (AB18001; NCT05211570], according to a press release from AB Science.1

The patient had a reduction from 55% to 5% in bone marrow blast cells 1 month after receiving the second-lowest dose increment used in the trial. They also experienced no treatment-related toxicities.

It is remarkable that we rapidly observed a response in what is typically a difficult-to-treat patient population of refractory AML. We observe a clear blast count reduction for this patient and excellent tolerance so far, Pau Montesinos, MD, hematologist at the La Fe University Hospital and coordinator of the Spanish group of acute myeloblastic leukemia (PETHEMA), stated in the press release. It is all the more noteworthy because the initial disappearance of leukemic cells was obtained after only 3 days of AB8939 treatment at a very low dose, with a good response maintained after a second 3-day cycle at this dose.

The microtubule destabilizer AB8939 has broad antitumor activity with the capability to overcome P-glycoprotein and myeloperoxidase-mediated resistance that reduces the efficacy of microtubule-targeting chemotherapies. In preclinical studies, it showed activity across all AML subtypes and in AML that displays resistance to azacitidine (Onureg).2 It was granted orphan drug designation for AML by the FDA.1

AML is a serious life-threatening condition and the most common cause of leukemia-related mortality, in large part because patients develop chemoresistance to existing frontline AML drugs, Olivier Hermine, MD, president of the Scientific Committee of AB Science and member of the Acadmie des Sciences in France, said in the press release.1

The AB18001 trial is a phase 1/2, open-label, multi-center, non-randomized, 2-part study that is planned to enroll an estimated 78 patients with relapsed or refractory AML or refractory myelodysplastic syndrome. The first part is a dose escalation study with a primary end point of safety, tolerability, and pharmacokinetic profiles of AB8939. The second part is a dose expansion study using a recommended phase 2 dose to study the schedule for a phase 2 trial and assess efficacy.

Patients are ineligible for the study if they are eligible for standard of care or hematopoietic stem cell transplantation, have active central nervous system leukemia, or acute promyelocytic leukemia.

The patient who had the bone marrow response was 65 years old and previously failed treatment with azacitidine and had a MECOM gene rearrangement which is a biomarker associated with resistance to standard chemotherapies and is linked to disease progression.1,3 Overexpression of MECOM occurs in approximately 10% of patients with AML, and they have poor prognosis. AB Science has submitted a provisional patent application for this subpopulation of patients with AML.

The patient received a 1.8 mg/m2 intravenous dose for 3 consecutive days on a 28-day cycle.3 They were noted for benefiting at the second lowest of 13 potential dose levels in the dose escalation part of the trial. They received further treatment with AB8939 at the request of the investigator. One month after the second treatment cycle of 3 consecutive days at the same dose, they maintained a good response of 10% bone marrow blasts, and a third treatment cycle was initiated.

The patient also had an increase in neutrophils from 200/Lto 260/L after the first cycle and 480/L after the end of the second cycle. They had an increase in platelet count from 3000/L to 11000/L after 1 cycle and 12000/L after 2 cycles of treatment.

Investigators reported that overall, there have been no signs of moderate, severe, or serious toxicities in the trial.1,3 Approximately 50% of patients enrolled have requested further treatment cycles after receiving the first cycle and a measurement at day 28. In addition, 70% of patients had an increase in platelets and 90% had an increase in neutrophils.3 The first 4 dose levels have been completed, with the fifth dose level cohort of 9.0 mg/m2 being ongoing.

AB Science is planning to complete phase 1 in 2023 and initiate phase 2 in 2023 or 2024. The planned design for phase 2 may involve patient selection based on MECOM and other genetic factors and will enroll fewer than 100 patients. [The] AML indication fits the criteria for accelerated approval pathway based on compelling phase 2 (FDA), hematological response being a validated surrogate endpoint of efficacy, they stated in the webcast.3

This preliminary clinical data provides the most encouraging signs to date that AB8939 may be well-suited for treatment of high-risk relapsed/refractory AML, said Hermine.1

REFERENCES

1. AB Science reports a first complete bone marrow response in a relapsed refractory acute myeloid leukemia patient from the very low dose arm of its AB8939 Phase I/II clinical trial (AB18001). News release. March 13, 2023. Accessed March 22, 2023. https://bit.ly/3JxnmJa

2. Hermine O, Humbert M, Goubard A, et al. B8939, a novel microtubule-destabilizing agent for the treatment of acute myeloid leukemia. Presented at: 2020 Annual Congress of the European Hematology Association; June 11-20, 2020; virtual. Accessed March 23, 2023. https://bit.ly/3LMnpUm

3. AB Science Webconference microtubule destabilizer agents (MDA). March 16, 2023. Accessed March 23, 2023. AB Science. https://bit.ly/3z20Kvq

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Complete Bone Response Observed in Trial of AB8939 for AML - Targeted Oncology

Living with leukaemia: ‘My ethnicity means I’ve only a 37% chance of … – inews

I didnt really notice when it all began. I just assumed, round about December, that I had flu. It was very odd, though, as it just wouldnt go away. I had it for five weeks. I tested myself for Covid. I just couldnt work out why it wouldnt go away.

I got antibiotics and steroids from my GP. I struggled to get an appointment because the nurses were on strike, so I didnt really know I had anything other than flu and a really bad sore throat I even went hoarse as well.

I was about to start a new job on 16 January this year, so on the day before I said to my husband Im going to A&E, because I wanted to start the new job and feel healthy, and I felt so unwell.

Whenever my husband and I go to A&E we always drop each other off, we never stay with each other because we know its going to take at least four hours to be seen. So I went in and they did all the various tests. They did a blood test and this particular doctor came up to me and told me that they were going to have to keep me in longer. I said no. no, no. I start a new job on Monday. But she said: Janice, you cannot go anywhere. You have leukaemia. You have blood cancer.

I asked if they had made a mistake and then phoned my husband telling him he better come to the hospital. Thats all how it started. Me just wanting to find out what was going on. Then another doctor came in and confirmed it with my husband there, as I was in disbelief at this stage.

My white blood cells count was 136. If it was a mistake my white blood cells would have been between 5 and 26. You cannot make a mistake with 136. Then they left the room, closed the curtain and thats when it really hit me. I wouldnt even say crying, I was bawling my eyes out. It was horrible. My husband was just hugging me.

I just thought this cant be real. I donate blood. I run. I do the odd Tesco cancer research run, I do the Macmillan one. I do all these runs raising money for charity and Im one of those people now. I couldnt believe it. I was shocked.

I was in Hillingdon Hospital, near Hayes, west London, for two days then they transferred me to Hammersmith Hospital and I was there for 42 days receiving chemotherapy treatment via IV and tablets, and other medications as well. I had blood transfusions 10 units of blood, 14 units of platelets. It was so much.

I knew within my community Im 56 and of Black British Caribbean descent, with Grenadian heritage that what I do need is a stem cell donor. And we dont donate enough blood, certainly not stem cells. So, from the get go, I wasnt going to lie down and cry. Im going to start raising awareness and thats exactly what Ive done.

I contacted Antony Nolan [the blood cancer charity] who saw my own posters, which said If I cannot save myself, maybe I can save someone else, and how much I was doing to raise awareness, we teamed up. Being positive has been my drive.

The place where I was going to work were willing to hold it for a couple of weeks, but it turned out I was in hospital for six weeks and sick with it as well so it would have been unfair, really. I wouldnt have had the strength to work. This is the first time in my life, since I was 17, that I havent been working. Ive always worked.

Im still in Hammersmith Hospital and going to be coming here for another four months so it wasnt worth thinking about work. The hospital lets you go home for your sanity for a week or 10 days or so. Now Im back for another month for all the treatment again. If youre okay the cycle repeats itself. Theyll keep doing that for five months. Hopefully, in the interim, theyll be looking for a donor.

They tried my two brothers and my sister but they were not a match because our antibodies conflicted. It takes about four weeks for them to do the initial blood test to wait to see if youre a match with your siblings. I had no doubt they would be a match 100 per cent Im going to be saved. Everything will be fine. On 8 March I got a call at home to say they were not a match. The older you get your antibodies change through having children, an infection, any sort of illness they are your defence mechanism. Theyre special for you and build up an immune system specifically for you. So I guess my siblings, whatever theyve had in their life, their antibodies have built up an immune system which conflicts with mine now.

I was just as devastated as when they told me I had leukaemia and I cried just the same, let me tell you. They also said there were no matches on any stem cell register around the world, so I kind of lost hope. What am I going to do? My brothers and sisters were supposed to be a 100 per cent match.

My two daughters are a 50 per cent match, meaning their antibodies might not be a problem so the doctors are going to look at them as a potential new option if something can be worked out. Im now waiting another month while they are tested. Its a waiting game. We dont know whats going to happen. I remain positive and hopeful that it has to be. Its very daunting.

The big issue for me is how difficult it is for non-White people to find a match [Currently people from a minority ethnic background have just a 37 per cent chance of finding an unrelated stem cell donor on the register, compared to 72 per cent for white Northern European patients]. I knew within the ethnic minority community we just dont donate enough, so I reached out to family and friends, my work colleagues. We know a lot of people between us all. I was targeting everyone of any colour my White friends, my Asian friends, they must know Black people just reach out and get the word out there.

In hospital, I have nine days of IV chemo and you get that twice a day. I feel fine with that one but now Im on a twice-a-day, 14-day chemo which makes me feel very nauseous, but they give you anti-sickness medication to help. If youre really bad they give you a shot in the arm, so theyre on board with any kind of side effects. The tablets really take it out of me though, so most of the time Im in bed. But I get up and try and do something.

Before I was sick I used to do my 10,000 steps a day. In here I cant really go that far walking in the room or in the corridor but Id do about 2,000 steps when I can, if Im well enough. Then its whether I need a blood or platelet transfusion. I think I respond well to treatment, because Ive always been a positive, strong person. If youre positive and strong that helps with our illnesses, Ive always thought. If youre wallowing in sorrow and feeling sorry for yourself, I dont think that helps at all.

So through this journey, every time the doctors come in theyve been very impressed with me. I say to people this is a temporary inconvenience and that is how Im going to see it. Although I dont want to be in hospital, if I was at home Id be cooking, cleaning, doing the washing Im seeing this as a holiday as well. I dont have to think about what to cook. I get three meals a day, I get my bed changed, I mean come on! I have to look at it positively.

I was told it normally takes between three and five months to find a donor. Usually, there is something they can do even if it is not a full match. Theres no real date. Its a waiting game. I cannot be on this treatment forever as youre prone to infection and its not good for your body anyway.

Ive set up a family WhatsApp group for daily updates as when everyone heard they were all devastated of course. My father died of prostate cancer 11 years ago. We saw how he went from being medium-sized to skin and bones. It was awful, so my family were so worried and thought the same thing would happen to me. Even I thought the same thing when I first heard my diagnosis. Am I going to lose my hair and am I going to die? Well, I did lose my hair, but Im still here, thank God.

Me being so positive is keeping my family upbeat and strong as well. They are all rooting for me. If Im feeling down I put it on the group chat, but most of the time its all positive. Believe you me, I really want to go home.

For more information about stem cell donation visit the following websites:

https://www.dkms.org.uk/

https://www.anthonynolan.org

htttps://wmda.info/

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Living with leukaemia: 'My ethnicity means I've only a 37% chance of ... - inews

Abbas Assesses the Use of Allogenic Transplant In MPNs – Targeted Oncology

CASE SUMMARY

A 68-year-old woman presented to her physician with symptoms of mild fatigue, moderate night sweats and abdominal pain/fullness lasting 4 months; she also reported increased bruising and unexplained weight loss. Her spleen was palpable 8 cm below the left costal margin. Genetic testing showed she was negative for a JAK2V617F or CALR mutation. Her karyotype was 46XX and a bone marrow biopsy showed megakaryocyteproliferation and atypia with evidenceof reticulin fibrosis.

A blood smear revealedleukoerythroblastosis and she was diagnosed with primary myelofibrosis with a DIPSS (Dynamic International Prognostic Scoring System) risk score of intermediate-2 and also had an intermediate MIPSS70 risk score.

DISCUSSION QUESTIONS

In your practice:

JONATHAN ABBAS, MD: Is this a patient where from day 1 youre talking about an allogeneic [hematopoietic stem cell] transplant [HSCT] referral? Is this a patient that a transplanter would want to see early in the disease course or is this something that you might want to hold off on a HSCT consult until something isn't behaving as well as it could?

Jonathan Abbas, MD

Director, Acute Leukemia Program

Ascension St. Thomas Midtown Hospital

Tennessee Oncology

Nashville, TN

JEREMY PANTIN, MD: The [patient is] approaching the age limit where things are going to start getting [difficult] and not somebody that we'll take straight to allogeneic HSCT transplant, but you probably want to consider therapy to reduce that spleen size. If the patient appears to not have comorbidities and may be a good candidate for HSCT, the intermediate-2 or greater risk will certainly allow them to move forward, in terms of the favorable risk-to-benefit ration, if everything is aligned.

MICHAEL T. BYRNE, MD: I think we used to argue about this, not argue [necessarily], but these were the hard patients because nobody knows what to do with them. She's the right age for transplant, but also, transplant is not without risk. Quality of life is probably worse after an allogeneic HSCT than it could be without, so I don't know. I think you plug her in then you see what her donor search looks like, and regardless of whether she goes to treatment, I think this is somebody that you probably treat if for no other reason than to try and improve her quality of life.

OLALEKAN O. OLUWOLE, MBBS, MD: I completely agree with what my colleague just said. We have several targeted therapies in this area, and we can just find 1 to give them to control their symptoms.1 If that fails, there will be another. There are many in development, so for those who are not keen on getting transplanted, there is a viable pathway to just keep treating them. Now for the patient who says, I want to see what the odds are, like what [Dr. Bryne] said, find out if they have a donor, talk about the risk-benefit, and go for it.

ABBAS: From my HSCT days, I would totally agree with you. I think this is a patient I would want to see early, to explain that you might not need me now, but you might need me one day. You've potentially got years left of transplant eligibility, and we dont have a crystal ball about how your response to treatment is going to be and where this disease is going.

Then just to be the devil's advocate for the case, this is a lucky one where we had intermediate risk with 1% blasts. If this [patient] had 6% or 7% of 8% blasts and we were now nudging closer to high risk, that might sway all of us to maybe think initially therapy might be more of a bridge to HSCT, because there might be a little bit less stable disease.

[This] is a symptomatic patient. Is there anybody out there who would watch and wait with this patient regardless of whether they are seeing the allogeneic HSCT team or not? Or does everyone feel this patient warrants some therapy?

RYAN CARR, MD: Yes, based on her symptoms, if you tried to watch and wait, so [the patient] might end up seeing somebody else.

ABBAS: I agree with you. She will certainly be finding another group in town if you said, You have [myelofibrosis], but it's not that big a deal. Let's just see you back in 3 months. I think it's unanimous this is a [patient] who's not a watch-and-wait case. They are out there, but this is not her.

CASE UPDATE

Additional lab values showed the following counts:

DISCUSSION QUESTIONS

ABBAS: [If there is] thrombocytopenia at baseline, I guess we have 2 options for this. One would be; are we comfortable still sticking with ruxolitinib [Jakafi], which we all agree on [in a patient case like this], but dose modifying potentially for thrombocytopenia or would just any thrombocytopenia necessarily make us think about another agent, if anybody wants to weigh in on it?

BRYNE: I think a thrombocytopenia of 140 109/L is different than thrombocytopenia of 30 109/L. That's quite a difference [between the level where a patient should receive] ruxolitinib vs pacritinib [Vonjo].

ABBAS: Yes, I would agree with you. Without the specific measurements, it's hard to say. Just also remember you certainly can, and we've been doing for years is dose decreasing the ruxolitinib with a lot of benefit.2 Unless you're in that extreme situation like down below 50 109/L platelet count, I still think there's a window to go with the tried and true [method here].

How about frailty? How about if this woman, let's say she was extremely frail and it wasn't necessarily a disease-related frailty, just other comorbidities? Would that sway us? Do we feel that JAK inhibitors are particularly tough on patients? Would this factor in at all if she were 78 years old or if she was 88 years old?

JACK ERTER, MD: No. I think this drug is, all things considered, quite on target and easy to take for most patients. I would certainly have no hesitation to give an 88-year-old a trial at a dose-modified start of ruxolitinib.

References

1. Li B, Rampal RK, Xiao Z. Targeted therapies for myeloproliferative neoplasms. Biomark Res. 2019 Jul 16;7:15. doi: 10.1186/s40364-019-0166-y

2. Mesa RA, Cortes J. Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. J Hematol Oncol. 2013 Oct 22;6:79. doi: 10.1186/1756-8722-6-79

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Abbas Assesses the Use of Allogenic Transplant In MPNs - Targeted Oncology