Stem Cell Clinic

Cell Therapy Prevents Risk Of Heart Attack or Stroke: Study – Forbes

All organs in the body rely on the blood and oxygen circulated by the heart. If the muscles of the heart weaken or stiffen too much, the heartalthough still beatingcan no longer pump enough to sustain other organs. This progressive condition called heart failure presently affects more than 6 million adults in the United States. Current treatments can delay but not permanently alter the course of the disease, leaving many patients with poor prognoses. A recent study published in the Journal of the American College of Cardiology searches for a permanent solution to repair the heart via stem cell therapy.

What are Mesenchymal Stem Cells?

Mesenchymal precursor cells (MPCs) refer to a small population of adult stem cells found in the bone marrow and select tissues. While embryonic stem cells can develop into any cell type in the body, mesenchymal stem cells develop into a defined variety of specialized cells. As Figure 1 illustrates, differentiation of these cells can create connective tissue cells, cartilage cells, white fat cells, bone cells and muscle cells. The ability to regenerate muscle cells is of notable interest in discussions around healing damaged hearts.

Mesenchymal precursor cells demonstrate other unique abilities. Preclinical studies suggest that these precursor cells may reduce inflammation driven by macrophages, immune cells involved in the bodys healing processes, and chemicals called cytokines. These stem cells also release proteins which promote the growth of new blood vessels and reverse the narrowing of arteries. These two characteristics may address critical mechanisms which contribute to heart failure: acute and chronic inflammation alongside restricted blood flow to the hearts tissues.

Clinical Trial Design

For their study, Perin et al. assessed the efficacy of mesenchymal precursor cell therapy on over 500 patients with moderate to severe heart failure. To do this, they first crafted their stem cell product. The researchers derived the stem cells from the bone marrow of three healthy adult donors. They then isolated and proliferated the stem cells before preserving them in liquid nitrogen.

Of all the hearts chambers, the team focused on the left ventricle. Figure 2 highlights the structure. This section of the heart provides the most pumping power and often falters first for people with heart failure. Left ventricular performance is therefore an important marker of the hearts condition.

Half of the study population received at least one dose of the cell therapy injection (see Figure 3) into the left ventricle. In contrast, the other halfthe control groupunderwent a procedure to remove a catheter from the left ventricle. The researchers then conducted site follow-ups 10 days after and on months 1, 3, 6 and 12. After month 12, the patients returned to the site every six months. The team followed the patients for around 30 months on average.

Study Endpoints and Measurements

The study contained two main objectives to understand the potential benefits of the intervention. The primary endpoint measured whether the therapy prolonged the time to a patients next nonfatal hospitalization or urgent care visit; it was considered a terminal event if a patients left ventricle failed to provide the majority or any of the hearts output. The secondary measurement recorded both the primary endpoint and the time to death.

Guided by a previous study, the team monitored left ventricular function and markers of inflammation for additional analysis. Left ventricular performance plays a major role in determining heart failure, while high baseline levels of high-sensitivity C-reactive protein (hsCRP)a marker of inflammationin patient plasma is associated with adverse cardiac events.

Mixed Results

The clinical trial yielded mixed results. The team found no significant difference between the treatment groups for the studys primary and secondary endpoints, suggesting that the therapy did not succeed. However, the therapy produced major findings related to heart function which hold great promise for future research.

Inflammation, Heart Attack and Non Fatal Stroke

The team noticed that adverse heart events could be stratified by inflammation. A single stem cell injection resulted in a 67% reduction in heart attack and a 56% reduction in stroke compared to controls. Figure 4 illustrates the clear difference in risk. Interestingly, the supposed benefit increased if the patient displayed higher levels of inflammation (see Figure 5).

Additionally, the therapy led to a modest reduction38% specificallyin three point major adverse cardiovascular events. This is categorized by a cardiovascular death, nonfatal heart attack or nonfatal stroke. Patients with more detectable inflammation saw a larger effect here, as well.

Inflammation and the Left Ventricle

The team used echocardiographic imaging to glean information about the left ventricle. They recorded three measurements in particular: left ventricular ejection fraction (LVEF), or how much blood the left ventricle pumps out during each heartbeat; left ventricular end-systolic volume (LVESV), or how blood remains in the chamber after a heartbeat; and left ventricular end diastolic volume (LVEDV), how much blood is in the chamber before a heart beat.

The patients who received the cell therapy experienced a small but statistically significant improvement in their hearts ability to pump over the course of a year. This is mostly attributed to the effect experienced by patients with higher levels of inflammation. In comparison, the therapy did not influence the left ventricular diastolic volume when compared to controls.

Possible Mechanisms

The clinical hope for cell therapy is to harness the self-renewing and tissue regenerating capabilities of stem cells to heal and repair the body. The mesenchymal stem cells injection in this study did not meet this goal; the therapy failed to reduce time to nonfatal hospitalization and all cause death for patients with heart failure. However, an interesting discovery did emerge regarding inflammation.

The stem cell therapy created by Perin et al. yielded larger perceived benefits for patients with higher detectable levels of inflammation. Heart attack, stroke and left ventricular function appeared to improve for patients with evidence of systemic inflammation. How could this difference be explained?

Background research suggests that targeting inflammation could reduce negative heart events. Animal studies of heart failure demonstrated how mesenchymal precursor cells could rebuild and generate new blood vessels; they, too, could reverse the narrowing of arteries throughout the heart and body in the presence of systemic inflammation. The authors posit, then, that their cell therapy may alter inflammatory environments in the heart and promote blood flow through the formation of new blood vessels.

The cytokines found around the heart may activate the mesenchymal cells, causing the stem cells to subsequently release proteins which suppress inflammation and encourage blood vessel formation. The anti-inflammatory effects likely reduce nonfatal heart attack, stroke and death for patients with high inflammation. On the other hand, the new blood vessels likely improve the function of the left ventricle, as noted in the study.

As the stem cells appear to target local and systemic inflammatory changes seen in heart failure and atherosclerosis (plaque-filled arteries), Perin et al. turn to inflammation as a possible therapeutic target for heart failure. The therapy, when used in conjunction with existing heart failure treatments, may provide additional clinical benefit to patients with increased inflammation.

Future Implications

This clinical trial marks an important step in the journey to use cell therapy to reverse heart failure. Although the therapy did not prevent hospitalization as initially hoped, the researchers found that a single stem cell injection reduced the risk of heart attack or stroke by more than 50% for people with heart failure. Stem cell therapy may be a complementary addition to heart failure treatment regimes in the future, but further research is needed to ascertain its promise.

I am a scientist, businessman, author, and philanthropist. For nearly two decades, I was a professor at Harvard Medical School and Harvard School of Public Health where I founded two academic research departments, the Division of Biochemical Pharmacology and the Division of Human Retrovirology. I am perhaps most well known for my work on cancer, HIV/AIDS, genomics and, today, on COVID-19. My autobiography, My Lifelong Fight Against Disease, publishes this October. I am chair and president of ACCESS Health International, a nonprofit organization I founded that fosters innovative solutions to the greatest health challenges of our day. Each of my articles at Forbes.com will focus on a specific healthcare challenge and offer best practices and innovative solutions to overcome those challenges for the benefit of all.

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Cell Therapy Prevents Risk Of Heart Attack or Stroke: Study - Forbes

Rise in Prostate Cancer Cases Contributes to Challenges in Care – Targeted Oncology

Murugesan Manoharan, MD, FRACS

Troubling news about prostate cancer emerged from the American Cancer Society (ACS) in January. In its Cancer Statistics 2023 study1, published in the journal CA: A Cancer Journal for Clinicians, ACS scientists announced:

These findings are due in part to the US Preventive Services Task Forces 2012 recommendation to cease PSA screening in all men. Since then, early diagnosis and treatment of prostate cancer has dropped, while advanced prostate cancer cases have begun a steady rise.

I have observed several factors in play at Miami Cancer Institute as we respond to the challenge of prostate cancer.

Cost of PSA Screening

I concur with the ACS recommendation that men of all ages should have an opportunity to make an informed decision about whether prostate cancer screening is right for them. Balanced and unbiased counsel from the physician is vital. However, the cost of testing may be a barrier for some patients, as many insurance plans do not cover it. I have observed that wealthier patients in urban areas are more likely to have access to timely screening, while lower-income and minority individuals do not. The latter group includes many of my patients in the Haitian American community, who have a significant incidence of aggressive prostate cancer.

Plentiful Treatment Options

The array of prostate cancer treatments includes robotic surgery, external beam radiation including proton beam therapy, brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), laser ablation, hormone and other drug therapy, chemotherapy, immunotherapy, and more. Direct-to-consumer marketing touting these various treatments can confuse and overwhelm patients. Again, careful consultation with an unbiased urologic oncologist is critical.

Image Credit Sheitipaves [stock.adobe.com

FDA Reviews

While the US is quite advanced in prostate cancer treatment, The FDAs ultra-cautious approach to approvals results in a lag in new-technology adoption.

For example, prostate specific membrane antigen (PSMA PET Imaging, which can accurately detect the spread of prostate cancer spread using a radioactive tracer, has been in use internationally since around 2014, but the FDA delayed its broad national approval of this technology until 2021.

High Intensity Focused Ultrasound (HIFU) therapy was studied as early as the 1940s and researchers focused on HIFU for the prostate in the 1990s. The treatment was approved in more than 20 countries, including Canada and Australia, before finally receiving FDA approval in 2015.

Last, the NanoKnife system, which employs low-energy, direct-current electrical pulses to destroy cancerous cells,was first made commercially available in 2009 but the FDA approved a pilot study only in 2019.

These technologies were widely used in cancer centers around the US prior to full FDA approval but since they werent covered by insurance, they were out of reach for many patients who could have benefited.

Promoting Good Quality-of-Life

Death isnt the only outcome of a prostate cancer diagnosis. The statistics dont account for the pain, suffering, and inconvenience patients may endure while undergoing treatment. My team and I focus on helping patients maintain a good quality of life while we work towards a cure. Our patients express several priorities as they prepare for prostate cancer treatment:

A quick recovery: patients want to get back to work and everyday living. Technological advances such as minimally invasive surgery (sometimes with a single small incision) help make this possible. Many patients go home 24 hours after surgery. Once their pain can be managed without narcotics, they can usually resume driving and other daily tasks.

Reliable urinary function: patients frequently express concerns about incontinence. Twenty years ago, some 10 percent of patients were left incontinent by prostate surgery. Because we are now able to better protect the nerve bundles and urinary sphincter during surgery, 98 percent of patients do not need pads one year after surgery.

A healthy sex life: while measuring sexual potency is subjective, I advise patients that if they are potent before surgery, theres a 75 to 90 percent chance they will remain potent after nerve-sparing surgery.

Managing treatment: traditional radiation treatments can require up to 6 weeks of daily hospital visits, a burdensome task for patients who are trying to hold down a job. Hyperfractionated radiotherapy uses higher doses of radiation spread over fewer days, allowing patients to keep a regular work schedule. Ablation therapy requires even less of a time commitment.

Novel treatment strategies

Novel treatment like theranostics are on the rise. Theranostics combines therapeutic, radioactive pharmaceutical particles with diagnostic imaging to examine cancerous cells. In prostate cancer patients, a PSMA PET scan is done to evaluate for metastatic disease. PSMA, or prostate-specific membrane antigen, is expressed by virtually all prostate cancers and its presence locates the cancerous cells accurately. When these cells and receptors are located, a theranostic medicine such as Lutetium-177 in combination with PSMA is administered, which binds to and kills the cancerous cells. Its use is currently limited to prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer.

Training

As prostate cancer diagnoses continue to rise, todays physicians have a duty to prepare the next generation in the fight. Miami Cancer Institute, in concert with Florida International Universitys Herbert Wertheim College of Medicine, offers a two-year Urologic Oncology fellowship covering all treatment modalities.

We also work with Year 3 and 4 medical students who havent yet chosen a specialty. Its my job to introduce them to the challenges of our super-specialty and pique their interest in pursuing urologic oncological surgery.

Lastly, we support working physicians who desire to continue their education in the specialty. My colleagues and I offer surgical observation opportunities for local physicians as well as participate in international training programs.

The advent of teleconferencing has created exciting new training opportunities. We offer bimonthly telemedicine webinars through Baptist Urological Academy to an international audience. Many participating physicians and fellows become recognized urologic oncologists in their own countries.

Managing prostate cancer starts with screening and early diagnosis but extends into the effective management of prostate cancer. It requires constructive participation of all involved in the prostate cancer management including the government, health institutions, physicians, health care staff and most importantly, the patients.

REFERENCES

1, Siegel RL,Miller KD,Wagle, NS,and Jemal A, A.Cancer statistics, 2023.CA Cancer J Clin2023;73(1):17-48. doi:10.3322/caac.21763

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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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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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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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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