CAR T-cell therapy treatment helps cancer patient beat near impossible odds – ABC News

A cancer patient who was given less than a two per cent chance of survival has beaten the odds thanks to a new treatment that alters patient's immune cells to recognise and fight cancer.

Troy Daley was the first person in Australia to trial CAR T-cell therapy to treat mantle cell lymphoma.

The 45-year-old's ordeal began when he discovered a lump in his groin during a shower in 2014 and went to his GP.

"The next thing I knew I was on the operating table having biopsies done and scans done," he said.

About a week later, he was diagnosed with Mantle cell lymphoma a rare type of non-Hodgkin lymphoma.

When Mr Daley was initially diagnosed, his GP told him there was a 98 per cent chance he would be dead within the next six months.

"Telling the family's probably the hardest thing I've ever had to do," he said.

"I had a bit of a slack night that night and the next day I woke up and decided I was too young to fall over and got the gloves on."

Mr Daley was admitted to the Lismore Base Hospital for chemotherapy and received a stem cell transplant in Brisbane, but the treatments were not match for the aggressive cancer.

"(It) came back pretty quick, within sort of six to eight months it was a bit of a shock to everybody," he said.

Mr Daley's haematologist, Dr Dan Scott said he was put on cancer drug Ibrutinib, which worked initially, but after two-and-a-half years his condition progressed.

The next step would have been a bone marrow transplant, but despite a world-wide pool of donors no suitable match could be found.

With almost all the options exhausted, Mr Daley was registered with a clinical trial being done at the Peter MacCallum Cancer Centre in Melbourne.

"It was at a stage where we've got to have a go at something," he said.

"We're not going to sit back here and let the gods come and get me."

CAR T-cell therapy is a new form of immunotherapy that uses specially altered T-cells to directly and precisely target cancer cells.

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Dr Scott said the CAR T-cell trial was used in conjunction with ibrutinib to treat Mr Daley's cancer.

"That's what's been exciting and different about Troy's case is he's had access to this therapy, which is relatively unusual in this disease," he said.

Dr Scott said the results have far exceeded expectations.

He said a recent PET CT scan showed "no evidence of lymphoma".

"We've also done a bone marrow biopsy recent where we look under a microscope and look for any evidence of residual lymphoma and there was no evidence in Troy's case," Dr Scott said.

A third test, which involves looking for traces of lymphoma beyond a microscopic level, has also come back clear.

"At this point in time the results are as good as we could have ever hoped for," Dr Scott said.

Mr Daley said the results were "10 times better" than anyone could have predicted.

"Within 28 days we've had more success than we've had in five years," he said.

"We don't exactly know what the future holds but at this stage, for what I've been through I couldn't be any better."

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CAR T-cell therapy treatment helps cancer patient beat near impossible odds - ABC News

Correlation of whole-bone marrow dual-time-point (18)F-FDG, as measured by a CT-based method of PET/CT quantification, with response to treatment in…

This article was originally published here

Am J Nucl Med Mol Imaging. 2020 Oct 15;10(5):257-264. eCollection 2020.

ABSTRACT

The practical application of dual-time-point-imaging (DTPI) technique still remains controversial. One of the issues is that current parameters of DTPI quantification suffer from some deficiencies, mainly limited sampling of the diseased sites by confining measurements to specific locations. We aimed to examine the correlation between the percent change from early to delayed scans in whole-bone marrow (WBM) 18F-FDG uptake, as measured by a CT-based method of PET/CT quantification, and response to treatment in multiple myeloma (MM) patients. Pre-treatment 18F-FDG-PET/CT scans of 36 newly diagnosed MM patients were collected in a prospective study at 1 h and 3 h post tracer injection (NCT02187731). A threshold algorithm based on bone Hounsfield units on CT was applied to segment and quantify WBM 18F-FDG uptake. Patients were separated into two treatment groups: high-dose therapy with autologous stem cell transplant (HDT) and non-high dose therapy (non-HDT). The International Response Criteria for MM patients was used to determine each patients response to treatment. In the HDT group, WBM 18F-FDG uptake increased significantly in patients that had a poor response to treatment, from a median of 1.31 (IQR: 1.13-1.64) at 1 h to a median of 1.85 (1.45-2.10) at 3 h. The median percent change was 37.77% (IQR: 23.47-46.4), with a range of 6.10-50.73 (P = 0.003). However, no significant change in uptake was observed in patients with a complete response (P = 0.24). The same trend was observed for the non-HDT group. WBM uptake of 18F-FDG assessed with dual-time-point imaging may have a role in predicting treatment response in MM.

PMID:33224622 | PMC:PMC7675111

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Correlation of whole-bone marrow dual-time-point (18)F-FDG, as measured by a CT-based method of PET/CT quantification, with response to treatment in...

Late Effects of Therapy Plague Many Patients Who Survived AML as Youths, Young Adults – AJMC.com Managed Markets Network

Most people who are diagnosed with AML are middle-aged or older. The American Cancer Society estimates the average age of a patient at AML diagnosis is 68. However, a small portion of patients will develop the disease in childhood or young adulthood.

Lead author Renata Abraho, MD, MSc, PhD, of the UC Davis Comprehensive Cancer Center, and colleagues, noted that treatments for patients with AML are typically similar regardless of the patients age. Generally, patients are given anthracycline- and cytarabine-based induction therapy, and then intensive chemotherapy or hematopoietic stem cell transplantation (HSCT). The differences, however, are that central nervous system-directed therapy is often used in pediatric patients, but not in adult patients, and that adolescents and young adults (AYAs) with AML receive HSCT at a higher rate than older patients.

Abraho said those aggressive treatment decisions for younger AML patients can be a mixed blessing.

Although these therapies may result in AML cure, they also contribute to late physical and psychosocial adverse effects in survivors, Abraho and colleagues wrote.

In hopes of gaining a better understanding of those effects, the investigators identified 1,168 AYAs with AML who were placed in the California Cancer Registry between 1996 and 2012 and who had survived at least 2 years following diagnosis. Those patients were followed through the year 2014, with hospital discharge data utilized in order to quantify possible late effects of their AML treatment.

The data showed that 10 years following diagnosis, more than a quarter of patients (26%) had developed an endocrine disease; 19% had developed cardiovascular disease; and 7% had developed a respiratory disease. Other serious illnesses were also identified, though at lower rates. Patients who underwent HSCT were twice as likely to experience most of the late effects, the investigators said.

Notably, however, the authors found that non-medical factors appeared to play a role in some of the outcomes. For instance, AYA survivors of AML were more likely to experience late effects if they had lived in a poor neighborhood at the time of their diagnosis. Hispanic, black and Asian/Pacific Islander survivors also faced increased risks.

The higher risk may relate to the financial hardship that patients with cancer often experience, said UC Davis Theresa Keegan, MS, PhD, the studys senior author, in a press release. As a result of cancer, AYA survivors and their families may miss work, experience income loss and incur substantial out-of-pocket expenses.

Keegan added that factors such as therapeutic management, patient response to treatment, and high-risk mutations in AML can also lead to a higher risk of after effects.

From a physician perspective, Abraho said the study data underscore the importance of vigilance even years after a diagnosis and cure.

Our findings can help clinicians and policymakers develop better survivorship care plans to reduce suffering and death among AYA survivors of AML, she said, in the press release.

Reference:

Abraho R, Huynh JC, Benjamin DJ, et al. Chronic medical conditions and late effects after acute myeloid leukaemia in adolescents and young adults: a population-based study, International Journal of Epidemiology doi: 10.1093/ije/dyaa184

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Late Effects of Therapy Plague Many Patients Who Survived AML as Youths, Young Adults - AJMC.com Managed Markets Network

Rescue Therapy with Bendamustine and Other Agents May Result in High Response Rates in Relapsed or Refractory NHL – Curetoday.com

Salvage chemotherapy, or treatment for cancer nonresponsive to other chemotherapy regimens, with bendamustine, ofatumumab, carboplatin and etoposide in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) served as a safe and effective regimen to bridge patients to stem cell transplantation.

In the era of high value, cost-conscious medicine, delivering high-quality care in the outpatient setting is becoming crucial to allow delivery of cost-effective care, the study authors wrote. (Bendamustine, ofatumumab, carboplatin and etoposide) offers a safe and effective outpatient alternative to currently available inpatient salvage chemotherapy regimens and has the potential to minimize hospitalizations and thus lower health care costs.

Aggressive salvage treatments commonly used in these patients are often administered in an inpatient or outpatient setting. A more ideal regimen, according to the study authors, would be administered in an outpatient setting, provide a favorable toxicity profile and high disease response rate and offer an alternative to CD20-targeted therapy, which focuses on a protein on the surface of B cells that also be found in bone marrow.

In this phase 1/2 study, 35 patients (median age, 62 years; 15 women) with relapsed or refractory aggressive B-cell NHL were treated with a salvage chemotherapy regimen including bendamustine, ofatumumab, carboplatin and etoposide. In particular, 57% of patients had de novo large cell or grade 3B follicular lymphoma, 26% had transformed de novo large cell lymphoma, 9% had grade 3A follicular lymphoma and 3% had mantle cell lymphoma.

The first cycle of this treatment was administered in an inpatient setting to monitor for infusion-related reactions. If toxicities of grade 3 or higher did not occur, which included severe, life-threatening events, subsequent cycles were given in an outpatient setting.

The primary objective of this study was to assess the tolerability and safety of this regimen and to determine its overall response rate (ORR). In addition, secondary end points included overall survival (OS), progression-free survival (PFS), duration of response and the number of patients who advanced to stem cell transplantation. Follow-up was conducted for a median of 24.1 months.

The ORR in all patients was 69%, with 49% of patients having a complete response and 20% of patients having a partial response. When patients with de novo large cell lymphoma and grade 3B follicular lymphoma were assessed, the ORR was 70%, with 50% of patients having a complete response and 20% of patients having a partial response.

Patients in the study had a median PFS of 5.1 months and OS of 26.2 months. Twelve patients moved on to undergo stem cell transplantation.

The most common grade 3-4 nonhematologic toxicities, or those not related to cancer originating in the bone marrow or blood, included hypophosphatemia and neutropenic fever. Hypophosphatemia refers to an electrolyte disorder resulting from low phosphate levels in blood, whereas neutropenic fever occurs when a patient has a temperature of 100.4 F or greater while having low counts of a type of white blood cell called neutrophil.

While the protocol mandated inpatient monitoring after the first cycle for (infusion-related reactions), we found that (infusion-related reactions) were all grade 1-2, the study authors wrote. Therefore, (bendamustine, ofatumumab, carboplatin and etoposide) should be safe for outpatient administration, which is our current institutional practice when using it outside of a clinical trial setting.

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Rescue Therapy with Bendamustine and Other Agents May Result in High Response Rates in Relapsed or Refractory NHL - Curetoday.com

Exploring First-line Therapies in Peripheral T-Cell Lymphomas – Targeted Oncology

During the Targeted Oncology Case Based Peer Perspectives event, Javier L. Munoz, MD, Hematologist/Oncologist Director, Lymphoma Program Mayo Clinic, discussed the case of 60-year-old patient with peripheral T-cell lymphoma (PTCL).

Targeted Oncology: What are the standard regimens in treating T-cell lymphoma?

MUNOZ: Historically, we have been prescribing CHOP [cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone] or CHOP-like regimens. There are retrospective German data showing the addition of etoposides, so CHOEP instead of CHOP, may be beneficial, particularly for patients who were younger than 65 years.1 That is not a randomized trial, it was a retrospective study, so the strength of the data was relatively weak.1 The data of brentuximab vedotin [Adcetris] plus CHP [cyclophosphamide, doxorubicin, prednisone] versus CHOP [was from] a randomized trial, so its a stronger level of evidence compared with that etoposide data.

What do the National Comprehensive Cancer Network (NCCN) guidelines recommend?

The category 1 recommendation for ALCL [anaplastic large cell lymphoma] is brentuximab vedotin plus CHP, according to the NCCN.2 For that particular indication, I think most people are not going to argue that brentuximab plus CHP is the way to go.

For the other subtypesand numbers for the other subtypes were smaller compared with ALCLits a bit more blurry. You still have brentuximab vedotin plus CHP, but you also have the options of CHOP, CHOEP.

What was the rationale for ECHELON-2 [NCT01777152] in this population? This was a randomized study, brentuximab vedotin plus CHP versus CHOP.3 The bottom line is that this trial was a replacement strategy. Vincristine, or Oncovin, is a vinca alkaloid, and it causes neuropathy. For brentuximab, an antibody-drug conjugate, its payload is also a vinca drug. Vinca alkaloids cause neuropathy, so the trial replaced those agents, resulting in this trial. It was a double-dummy, [double-blind] study, so patients received placebobrentuximab and CHP or they received CHOP. The CD30 expression needed to be 10% or higher for the patient to be able to enroll. The investigators allowed multiple subtypes of T-cell lymphomas: PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, enteropathy-associated T-cell lymphoma.

The reality is that most of you are going see PTCL, not otherwise specified, because its the most common subtype I see; maybe the runner-up is angioimmunoblastic T-cell lymphoma, and then the next one is going to be ALCL. And again, there are a couple of flavors: ALK-positive and ALK-negative. ALK-negative is, prognostically, closer to PTCL. The primary end point was progression-free survival [PFS] but, of course, they looked at other things like overall survival.3

What were the outcomes of this trial for patients? PFS was a primary end point, and this was the most important factor or variable that they looked at, and with CHOP you get 20.8 months of PFS; with brentuximab plus CHP you got 48.2 months. So, more than double the primary end point, and that is why I like to start with PTCL, because ECHELON-2 definitely looked more impressive than the ECHELON-1 trial [NCT01712490]. Theyre both important papers; ECHELON-1 was published in New England Journal of Medicine,4 ECHELON-2 was only published in Lancet. The difference, the numbers that you see, are more dramatic in ECHELON-2 in PTCL compared with Hodgkin lymphoma, but both are relevant papers. More than double the results, and you could see that that separation is maintained over time.

They looked at overall survival, and there was also a difference. Even though the primary end point was PFS, your patients are also going to live longer if you go with brentuximab plus CHP.

The complete response rate was 68% for [brentuximab vedotin plus CHP] versus 56% for CHOP. Of course, the objective response rate is also higher for brentuximab plus CHP, as well [TABLE5 ].

As I said, both drugs can potentially cause neuropathy. Lets take a look at the safety profile. Peripheral neuropathy for brentuximab plus CHP, grade 3 or higher, was 4%, for CHOP, it was 3%. Remember, vincristine in the CHOP regimen can also cause neuropathy. Not a big difference there. For any grade of neuropathy, the numbers are 45% for brentuximab plus CHP and 41% for CHOP.

Now, could you die from CHOP, or brentuximab plus CHP? Of course. Luckily for us, its single digits. Its rareIm sure that we have all had patients that we have lost during CHOP or R-CHOP [rituximab (Rituxan) plus CHOP] for B-cell lymphomas, but 3% for brentuximab plus CHP and 4% for CHOP.

If this patient achieved a complete response to frontline therapy, would you consider transplant?

Before the ECHELON trials, most of us knew that CHOP was suboptimal; we just did not know what was better than CHOP. Thats why we were playing with etoposide, based on that retrospective German data and doing CHOEP, sometimes even EPOCH [etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride] for these patients. Because CHOP was suboptimal, we wanted to do something additional, and that is why many patients have received consolidation with transplants.

We consider so many factors for transplant-eligible patientsthe performance status, comorbidities, age; but in general, Im prone to offer [transplant] to patients who have these T-cell lymphomas because, again, its a bad disease, and its not a curative intent. You are not giving the treatment with a curative intent. You want to keep the disease at bay as much as possible.

What is the impact of consolidative stem cell transplant after frontline brentuximab plus CHP for patients?

In a post hoc analysis, for the patients who achieved complete remission [CR], 38 patients in CR, received the transplant, and 76 patients in CR did not; it was certainly not the primary end point.5 It was presented at the American Society of Hematology Annual Meeting in 2019. Again, we are tempted to prescribe the transplant because, historically, these patients have done so poorly. The majority of these patients in CR after brentuximab plus CHP did not receive a transplant, 38 patients did receive a transplant, and it seems that the patients that received the consolidation with the transplant did better than the patients who did not receive the transplant. You have the 3-year progression-free survival numbers: 76% and 53%, though my bias at this point would be young, relatively young, or with few comorbidities, good performance statusI would certainly send the patient to get a second opinion.

What would be your approach toward second-line therapy at progression?

The number 1 option is a clinical trial. Id also consider pralatrexate [Folotyn]. Belinostat [Beleodaq], pralatrexate, and romidepsin [Istodax] are going to give an overall response somewhere between 20% to 30%, and complete remissions that are approximately 10%, give or take. Duration of response is usually going to be less than a year. Bottom line, we need to do better for PTCL when its relapsed/refractory. We need to do good when it comes to our frontline therapies, so, hopefully, we can provide a long period of time of remission for our patients.

References:

1. Schmitz N, Trmper L, Ziepert M, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German high-grade non-Hodgkin lymphoma study group. Blood. 2010;116(18):3418- 3425. doi:10.1182/blood-2010-02-270785

2. NCCN. Clinical practice guidelines in oncology. T-cell lymphomas, version 1.2021. Accessed October 14, 2020. https://bit.ly/3kcUHLL

3. Horwitz S, OConnor OA, Pro B, et al; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393(10168):229-240. doi:10.1016/S0140-6736(18)32984-2

4. Connors JM, Jurczak W, Straus DJ; ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV hodgkins lymphoma. N Engl J Med. 2018;378(4):331-344. doi: 10.1056/NEJMoa1708984

5. Savage KJ, Horwitz SM, Advani RH. An exploratory analysis of brentuximab vedotin plus chp (A+CHP) in the frontline treatment of patients with CD30+ peripheral T-cell lymphomas (ECHELON-2): impact of consolidative stem cell transplant. Blood. 2019; 134(suppl 1):464. doi:10.1182/blood-2019-122781

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Genenta to Appoint Stephen Squinto, Experienced Biotech Executive and Investor, as Chairman – BioSpace

MILAN, Italy and NEW YORK, Nov. 23, 2020 (GLOBE NEWSWIRE) -- Genenta Science, a clinical-stage biotechnology company pioneering the development of a hematopoietic stem progenitor cell gene therapy for cancer (Temferon), announced that highly experienced biotech executive and investor Stephen Squinto, PhD joint Genenta and will be appointed as Chairman of its Board of Directors.

The appointment will be effective with the approval of the Genenta Shareholders Meeting. Pierluigi Paracchi, currently Chairman and Chief Executive Officer of Genenta, will continue to serve as CEO.

Dr Squinto is currently Executive Partner of the healthcare investment company OrbiMed Advisors and has more than 25 years experience in the biotech industry, including as Chief Executive Officer of the gene therapy company Passage Bio. He was a co-founder of Alexion Pharmaceuticals, where he served as Chief Global Operations Officer and Global Head of Research, and previously held several senior leadership positions at Regeneron Pharmaceuticals.

Dr Squinto currently serves on the Board of Directors of a several biotech and healthcare companies and has received numerous honors and awards from academic and professional organizations for his scientific work. He received his PhD in Biochemistry and Biophysics from Loyola University of Chicago.

Pierluigi Paracchi, CEO of Genenta, said: I am delighted to welcome Steve Squinto to Genenta as our new Chairman. Steve will provide valuable input and guidance to the development on Genenta, based on his outstanding and extensive time in biotech industry. In particular, his time as CEO of the gene therapy company Passage Bio provides a clear parallel to Genenta, as we continue to develop the stem cell gene therapy Temferon.

Stephen Squinto said: It as honor to be invited to be Chairman of Genenta, a truly exciting company which has the potential to revolutionize the way we treat cancer through its novel immuno-gene therapy Temferon. I am looking forward to working with the outstanding team already in place to progress this treatment, which has potential against a broad range of tumors both as first line and as combination therapy, further through clinical trials and towards market.

About Genenta Science

Genenta (www.genenta.com) is a clinical-stage biotechnology company pioneering the development of a proprietary hematopoietic stem cell gene therapy for cancer. Temferon is based on ex-vivo gene transfer into autologous hematopoietic stem/progenitor cells (HSPCs) to deliver immunomodulatory molecules directly via tumor-infiltrating monocytes/macrophages (Tie2 Expressing Monocytes - TEMs). Temferon, which is under investigation in a Phase I/II clinical trial in newly diagnosed Glioblastoma Multiforme patients, is not restricted to pre-selected tumor antigens nor type and may reach solid tumors, one of the main unresolved challenge in immuno oncology. Based in Milan, Italy, and New York, USA, Genenta has raised 33.6 million (~$40 million ) in three separate rounds of financing.

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Israeli Scientists Discover Oxygen Beauty Treatment That Can Make You Look 25 Years Younger – All You Need to – India.com

Want to go back in time and look younger? Thats possible now. Yes, you read that right. In a path-breaking discovering, Israeli scientists have made reverse ageing possible. They have found a way to make you look up to 25 years younger. Also Read - Weight Lifting, Sleeping Face-Down And More: Here're 5 Lifestyle Habits That May be Ageing Your Skin

Researchers at Tel Aviv University and the Shamir Medical Centre have collaboratively conducted a study for which they enrolled 35 adults over 64. The subjects were given hyperbaric oxygen treatments (HBOT) 5 times a week for 90 minutes. This continued for three months. Later, the study results published in the journal Ageing showed that the use of this oxygen treatment shortened the ends of the chromosome (telomers) and reversed the accumulation of old body cells. Also Read - 3 Anti-Ageing Essential Oils That Can Offer You Youthful Skin

Notably, ageing depends upon sequences of DNA called telomeres. They are located at the ends of chromosomes and their function is to protect the genetic material contained within. These telomeres shorten and degrade every time a cell divides. This process keeps happening until they become so worn down that they can no longer function. This further results in an unstable or dead chromosome. Also Read - 5 Anti-Ageing Food Items You Must Include in Your Diet to Look Young

One of the study researchers named Professor Shai Efrati said, Today telomere shortening is considered the Holy Grail of the biology of ageing. Researchers around the world are trying to develop pharmacological and environmental interventions that enable telomere elongation. Our HBOT protocol was able to achieve this, proving that the ageing process can, in fact, be reversed at the basic cellular-molecular level.

Hyperbaric Oxygen Treatment (HBOT) is a type of therapy during which a patient is kept in a pressurized chamber where the level of oxygen is increased 3 to 4 times more than what you can breathe at normal air pressure. This aims at treating patients suffering from decompression sickness, brain abscess, severe anemia, who have developed air bubbles in their blood vessels, non-healing wounds, radiation injury, vision loss etc.

When your body gets extra oxygen, it releases growth factors and stem cells that are known to promote healing. In a normal scenario, the oxygen you get through the air is adequate for your body to perform different functions. However, when tissue in your body gets damaged or injured, it needs extra oxygen to survive. Through hyperbaric oxygen treatment, doctors temporarily increase the amount of blood your body is carrying and thus helps maintain the oxygen level in tissue to ensure its survival.

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Israeli Scientists Discover Oxygen Beauty Treatment That Can Make You Look 25 Years Younger - All You Need to - India.com

Novartis licenses phase 3 COVID-19 cell therapy from Mesoblast – FierceBiotech

Novartis has secured a global license to Mesoblasts cell therapy remestemcel-L in the treatment of COVID-19. The deal lands Mesoblast $50 million upfront and the support of a partner that could help address critical quality attribute concerns raised by the FDA.

Last month, the FDA rejected a filing for approval of the cell therapy in children with steroid-resistant graft-versus-host disease (GvHD). By then, Mesoblast had already begun testing the allogeneic cell therapy in COVID-19 patients with acute respiratory distress syndrome (ARDS). The phase 3 started in May is designed to validate signs of efficacy seen in a 12-patient compassionate use program.

Novartis has stepped in to help Mesoblast take remestemcel-L forward in ARDS. In return for a $25 million upfront payment and $25 million investment, plus milestones and royalties, Mesoblast has given Novartis a global license to develop and commercialize remestemcel-L in ARDS.

Evidence of the prospects of remestemcel-L, a mesenchymal stem cell therapy, in COVID-19-related ARDS is set to arrive when the 300-patient phase 3 trial wraps up early next year. If the trial is successful, Novartis plans to work with Mesoblast to develop appropriate critical quality attributes that meet [FDA] requirements for remestemcel-L.

The focus on critical quality attributes reflects the problems Mesoblast encountered when it tried to win FDA approval for remestemcel-L in GvHD earlier this year. In its briefing document, the FDA said the attributes do not have a demonstrated relationship to the clinical performance of specific [drug product] lots. The advisory committee backed the drug, but the FDA issued a complete response letter.

Novartis, which has an approved cell therapy, may have the expertise to ensure remestemcel-L fares better when up for review by the FDA as a treatment for ARDS in COVID-19 patients. Novartis will also provide support to enable commercial manufacturing scale-up. Mesoblast has previously said it needed to substantially scale up manufacturing to serve the COVID-19 market.

The relationship between the companies extends beyond COVID-19. Novartis plans to run a phase 3 trial in non-COVID-19 ARDS patients, setting it up to address the broader unmet medical need. ARDS causes 40% mortality in the around 200,000 patients who develop the condition in the U.S. annually.

Novartis also has an option to distribute remestemcel-L outside of Japan in GvHD and to co-fund its development and commercialization in other non-respiratory indications. Shares in Mesoblast rose 18% in response to the news. Even after the bump, the stock remains down on the highs it hit before the complete response letter.

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Benefits of Hematopoietic Stem Cell Transplantation in Advanced Myelodysplastic Syndromes – Hematology Advisor

Among fit older adults with advanced myelodysplastic syndromes (MDS) undergoing hematopoietic stem cell transplantation (HSCT), survival is significantly improved when transplantation is performed early or for adverse risk disease but not for patients with standard risk disease with severe cytopenia, according to study results published in Leukemia.

For patients with MDS, the median age at the time of diagnosis is approximately 70 years, and patients typically have an overall survival of 1 year in advanced disease. Although the only known curative therapy is HSCT, the study authors noted that The median age at diagnosis has historically limited the number of patients considered eligible for [HSCT]. This is because of the increased mortality linked to myeloablative conditioning regimens in this patient population. However, reduced-intensity conditioning (RIC) has allowed HSCT to be a treatment option for fit, elderly patients.

Gregory A. Abel, MD, MPH, of Dana-Farber Cancer Institute and Harvard School of Public Health, in Boston, Massachusetts, and associates conducted a prospective observational study to assess survival among patients aged 60 to 75 years with advanced MDS who were eligible for HSCT, and to compare RIC HSCT vs non-HSCT approaches in this patient population. The primary endpoint was overall survival.

Of the 303 eligible participants, 290 patients were enrolled in the study; 175 patients had MDS and 115 had severe cytopenia. The median age of the entire cohort was 69 years and nearly two-thirds of the population were men (65.5%). The median overall survival for the entire group was 29 months (95% CI, 19-39.5), the 3-year overall survival was 46% (95% CI, 40-52).

A total of 113 patients underwent HSCT (median time to HSCT, 5 months). Of the patients who underwent transplantation, 58 patients (51.2%) died. Of the 177 patients who did not undergo HSCT, 119 patients (71.3%) died.

In a univariable analysis comparing death in HSCT with no HSCT, the hazard ratio (HR) was 0.84 (P =.30). The HR for death for HSCT 5 months or sooner after enrollment (HR, 0.64; P =.04) and more than 5 months after enrollment (HR, 1.20; P =.39) were also measured.

In a multivariable analysis controlling for several factors, the HR for mortality among patients who underwent HSCT vs no HSCT was 0.75 (P =.13), and the HRs for adverse MDS risk and standard risk with severe cytopenia were 0.57 (P =.01) and 1.33 (P =.36), respectively.

[F]it adults with advanced MDS, a treatment strategy that included [HSCT] trended toward better overall survival, the investigators noted. There were also significant benefits for those receiving [HSCT] within 5 months and for those with adverse disease risk factors as compared to standard risk with severe cytopenias. Future studies should refine which subgroups of adverse risk patients benefit most, how genomics and measurable residual disease can be used to risk stratify consideration of [HSCT] in this patient population, and how recently characterized predictors, such as frailty, may be incorporated into these decisions, the authors concluded.

Abel GA, Kim HT, Hantel A, et al. Fit older adults with advanced myelodysplastic syndromes: who is most likely to benefit from transplant? Leukemia. Published online November 17, 2020. doi:10.1038/s41375-020-01092-2

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Benefits of Hematopoietic Stem Cell Transplantation in Advanced Myelodysplastic Syndromes - Hematology Advisor

YOUR HEALTH: Your body may already have the answer to knee pain – WQAD.com

DENVER It impacts a lot of us.

One in four people are living with knee pain.

"I think it was just a matter of wear and tear of over the years," said Al Perez who has had knee pain for years.

"Walking became difficult because I get some swelling and pain."

Perez had his right knee replaced eight years ago and he didn't want a repeat procedure on his left.

"I have some arthritis in that knee, osteoarthritis, and I wanted to avoid at all costs another knee replacement."

Perez found orthopedic surgeon Dr. Jason Dragoo at the Steadman Hawkins Clinic at UCHealth in Denver who is part of a team that made stem-cell history.

"It set off this revolution worldwide of getting STEM cells from fat," said Dr. Dragoo

And now, he's using those stem cells to ease his patients knee pain.

"Mother nature put in this piece of fat that's in our knee, it's called the fat pad," said Dr. Dragoo.

"And we looked at the fat pad and it contains a very high number of STEM cells."

From harvesting the cells to implant, the procedure takes about 20 minutes.

"We process them in the operating room and then give them back to patients during the same surgical procedures."

Dr. Dragoo said the best candidate is someone with moderate to middle-stage arthritis.

Initial studies show that the treatment reduces pain and inflammation.

Now, they are looking to see if the cartilage regrows.

He's four years post-surgery and his pain is gone.

"Within three, four days I was walking with barely a limp," said Perez. "I was good. I can walk 18 holes."

Three places in the United States perform this procedure:

Studies have shown that stem cells release factors that reside on opioid receptors. Those are one of the pain-relieving receptors that we have in our body and that is the reason that stem cell therapy is thought to decrease pain.

If this story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Jim Mertens atjim.mertens@wqad.comor Marjorie Bekaert Thomas atmthomas@ivanhoe.com.

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YOUR HEALTH: Your body may already have the answer to knee pain - WQAD.com