Coronavirus Update: Baptist Hospital Patient Credits Stem Cell Treatment With Saving Her Life – CBS Miami

MIAMI (CBSMiami) The U.S. Food and Drug Administration gave Baptist Health approval to test a stem cell treatment on COVID-19 patients and so far its come back with positive results.

The treatment has proven successful with three patients.

One of those patients, Ruth Ramirez says it saved her life.

Ramirez was discharged from the hospital on Friday afternoon.

They saved my life. They definitely saved my life, said Ramirez.

Ramirez recently received stem cells from an umbilical cord known as mesenchymal cells.

Mesenchymal stem cells have the ability to reduce cytokine levels, said doctor Guenther Koehne.

Baptist Hospital says patients like Ramirez showed a reduction of their oxygen requirement from 100% to less than 50% within days of the infusion, accompanied by a significant reduction in levels of various key circulating inflammatory markers.

I couldnt breathe. I had a fever a headache I was nauseous, said Ramirez.

Ruth, an employee of the Miami Cancer Institute, tested positive for COVID-19 back on April 7th. She was admitted to the ICU and ended up on a ventilator fighting for her life.

Knowing she may lose consciousness she gave her sister power of attorney. That is when doctors Koehne and Javier Perez Fernandez approached the family about this FDA approved experimental therapy.

Im a person who jumps. I jump with hope with the best outcome there is on the other side. I think she took that into consideration with my characteristic and said Ruth would probably do this.

According to friends, Ruth was in ICU for three weeks, on a ventilator, and unable to breathe on her own.

All that time, she was away from her two small kids. That was several days ago.

On Friday, she was discharged.

To be here in this room, alone, and not being able to hold them. It was hard you know its hard.

As soon as they told me that I was going home I was like what?? And that I tested negative again I was like wait!! That changed my mood completely

Still fuzzy on the timeline, Ruth says shes unsure where along the way she received the treatment but is thankful for the doctors and wants others to know there is hope.

You know I hear the bells here all the time the eye of the tiger thats the song that you walk out of when you come out with coronavirus. Its such a pleasure hearing it all the time now. More than I heard it yesterday.

Not only did the doctors step up, but so did her co-workers who set up this Ruthie-strong go fund me page to help with bills and expenses.

They also helped take care of her family.

They would send food to them. Groceries. My kids were taken care of my sister was taken care of. She didnt have to leave from the house.

Theyre just amazing.

The University of Miami is also working on a clinical trial using mesenchymal cells which we reported on in April.

Click here if you would like to donate to her GoFundMe page.

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Coronavirus Update: Baptist Hospital Patient Credits Stem Cell Treatment With Saving Her Life - CBS Miami

Investigational new drug may be beneficial in treating severe COVID-19 – BioNews

4 May 2020

A novel stem cell therapy may play a part in improving the survival rate of ventilator-dependent COVID-19 patients.

Twelve COVID-19 patients at Mount Sinai Hospital in New York were treated with a new type of stem cell therapy, resulting ina survival rate of 83 percent, significantly higher than the 12 percent survival rate for similar untreated patients.

Dr Keren Osman who led the team Mount Sinai Hospital, New Yorktold CBS News: 'What we saw in the very first patient was that within four hours of getting the cells, a lot of her parameters started to get better'.

Ryoncil (remestemcel-L) comprises culture-expanded mesenchymal stem cells (MSCs):rare cells that secrete factors that promote tissue repair and modulate an immune response.

The initial trial of Ryoncil with COVID-19 patients included two intravenous infusions of the drug over five days. Ten of the total 12 patients were able to come off ventilators after treatment. All patients had received other experimental therapies before receiving Ryoncil.

Dr Osman said 'we don't know if the ten people taken off ventilators would not have recovered if they had not been given the stem cell treatment and we would never dare to claim that it was related to the cells A randomised controlled trial would be the only way to make a true comparison.'

A300-person randomised, controlled clinical trial is now planned to determine the safety and efficacy of Ryoncil in the treatment of COVID-19 patients suffering from acute respiratory distress syndrome (ARDS), which results when the patient is unable to get enough oxygen and usually requires the use of a ventilator.

The overreaction of the immune system responsible for these effects is often termed a 'cytokine storm', where the systemic response to destroy the virus ends up damaging the infected lung tissue. Cytokines are small proteins released from certain cells in the immune system and play a role in cell signalling. Therapeutic use of Ryoncil is thought to down-regulate pro-inflammatory cytokine production and stimulate increased production of anti-inflammatory cytokines.

Ryoncil is currently under review by the US Food and Drug Administration (FDA) for the treatment of acute graft versus host diseaseand other rare diseases. The drug has been evaluated through several clinical trials, totalling over 1100 patients, including evidence of improved lung function in patients with similar biomarkers to COVID-19 patients with ARDS.

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Subcutaneous Formulation of Daratumumab Approved for Multiple Myeloma – Cancer Therapy Advisor

The Food and Drug Administration (FDA) has approved Darzalex Faspro (daratumumab and hyaluronidase-fihj; Janssen) for the treatment of newly diagnosed or relapsed/refractory multiple myeloma in adult patients.

Darzalex Faspro is a new subcutaneous (SC) formulation that contains daratumumab, a CD38-directed cytolytic antibody, with hyaluronidase, an endoglycosidase. The new SC formulation is administered over approximately 3 to 5 minutes compared with the intravenous (IV) formulation of daratumumab (Darzalex) that is administered over hours. Darzalex Faspro is indicated for the treatment of adult patients with multiple myeloma:

The approval was based on data from the phase 3 COLUMBA and the phase 2 PLEIADES studies. The open-label, noninferiority COLUMBA study evaluated the efficacy and safety of Darzalex Faspro monotherapy in 522 patients with refractory or relapsed multiple myeloma. Patients were randomized to receive either Darzalex Faspro (1800mg/30,000 units) SC or daratumumab 16mg/kg IV once weekly until unacceptable toxicity or disease progression. Results showed that Darzalex Faspro achieved noninferiority with an ORR of 41.1% compared with 37.1% for daratumumab (risk ratio [RR] 1.11; 95% CI, 0.89-1.37). The geometric mean ratio comparing Darzalex Faspro to daratumumab IV for maximum Ctrough was 108% (90% CI, 96-122).

Additionally, the multicenter, single-arm, phase 2 PLEIADES study assessed the efficacy and safety of Darzalex Faspro in combination with bortezomib, melphalan and prednisone in 67 patients with newly diagnosed multiple myeloma who were ineligible for transplant. Findings from this group of patients showed an ORR of 88.1% (95% CI, 77.8-94.7). Moreover, in PLEIADES, the combination of Darzalex Faspro with lenalidomide and dexamethasone was evaluated in 65 patients who had received at least 1 prior line of therapy. Results from this group showed an ORR of 90.8% (95% CI, 81.0-96.5).

With regard to safety, Darzalex Faspro demonstrated a similar profile to that observed with intravenous daratumumab. Moreover, treatment with Darzalex Faspro was associated with a significant reduction in systemic administration-related reactions compared with intravenous daratumumab (13% vs 34%, respectively).

Since the approval of daratumumab, a robust body of evidence has established its use as a treatment for multiple myeloma in both the frontline and relapsed and refractory settings, said Saad Z. Usmani, MD, Division Chief of Plasma Cell Disorders, Levine Cancer Institute. With Darzalex Faspro there may be fewer administration-related reactions compared to intravenous Darzalex, providing an additional treatment option that may help patients, oncologists and nursing staff.

Darzalex Faspro is expected to be available the week of May 11, 2020 in single-dose vials containing 1800mg daratumumab and 30,000 units hyaluronidase per 15mL. To prevent medication errors, the vial labels should be checked to ensure that the drug being prepared and administered is for subcutaneous use; Darzalex Faspro should not be administered intravenously.

The Company will also offer a copay savings card to assist patients.

For more information visit darzalex.com.

This article originally appeared on MPR

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Sam back home in Limehouse after treatment donating stem cells to help a patient beat blood cancer – East London Advertiser

PUBLISHED: 13:06 04 May 2020 | UPDATED: 13:18 04 May 2020

Mike Brooke

Sam in the London Clinic... after being matched to save a patient's life in worldwide appeal for stem cell donors. Picture: DKMS charity,

DKMS

A life-saving transplant procedure for Sam Schmidt to donate some of his blood stem cells to help save a patients life has gone well.

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The 24-year-old accounts manager from Limehouse was finally found to be a compatible match for a patient in a worldwide search after registering with a stem cell charity a year ago.

He underwent the procedure at The London Clinic before the weekend to donate stem cells after being successfully matched with a blood cancer patient.

He felt strange being tested due to Covid-19 with everyone having to wear masks and gloves, but felt lucky to have the chance potentially to save someones life and help a family.

Sam registered with the DKMS charity, known as We Delete Blood Cancer, when he moved to Narrow Street in Limehouse last year from west London.

He was inspired after learning about 42-year-old Peter McCleave, a father of two in Cheshire diagnosed with blood cell cancer and given a few years to live.

Peter has launched his own search for donors with his 10,000 people campaign while still waiting for a match. He has attracted potential donors to register with the DKMS Foundation, but so far has found no match to save his own life.

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Sam back home in Limehouse after treatment donating stem cells to help a patient beat blood cancer - East London Advertiser

Outcomes of Stem Cell Transplantation in Patients With Newly Diagnosed Transformed Fanconi Anemia – Hematology Advisor

Patientswith newly diagnosed transformed Fanconi anemia (FA) have poor outcomes andshould achieve complete remission (CR) prior to allogeneic hematopoietic stemcell transplantation (alloHSCT), according to results from a study published inthe American Journal of Hematology.

Stefano Giardino, MD, of the hematopoietic stem cell transplantation unit at the Istituto Giannina Gaslini in Italy, and colleagues retrospectively analyzed outcomes of 74 patients with transformed FA (36 male; median age, 14 years); 35 patients had myelodysplastic syndrome, 35 had acute leukemia, and 4 patients had high-risk cytogenetic abnormality. All patients underwent alloHSCT from 1999 to 2016.

The primary end points were overall survival (OS) and event-free survival (EFS). Secondary endpoints included the incidence of grade 2 to 4 acute graft-vs-host disease (AGVHD) and chronic graft-vs-host disease (CGVHD), non-relapse mortality (NRM), and incidence of relapse. To identify potential factors that may influence outcomes, the researchers assessed the type of diagnosis, preHSCT cytoreductive therapies and related toxicities, disease status prior to HSCT, donor type, and conditioning regimen.

Ata median follow-up of 7 years, 5-year OS and EFS were 42% and 39%,respectively; 5-year cumulative incidence relapse and NRM rates were 21% and40%, respectively. Patients in CR during transplant had better OS than those whostill had active disease (OS, 71% vs 37%, respectively; P =.04). No other factors had a significant effecton patient outcomes.

Of22 patients who received cytoreductive therapy prior to HSCT, 40.9% experienceda grade 3 to grade 4 toxicity event; this did not appear to effect survivalafter HSCT (3 year OS, toxicity preHSCT 48% vs no toxicity 51%; P =.98).At 100 days, the cumulative incidence of grade 2 to 4 AGVHD was 38%, and the cumulativeincidence of 5-year CGVHD was 40%.

At5 years, NRM was 40%, while incidence of relapse was 21%. Transplant-relatedevents were the cause of mortality in 81% of patients (34 of 42 deaths).

Limitationsof the study included the retrospective design and incomplete data for somevariables. The authors highlighted the large number of patients for this raredisorder as the primary strength.

Inorder to optimize the chances of the only curative option for FA in malignanttransformation, a sequential cytoreductive therapy followed by HSCT appears areasonable approach in FA patients with AL, if a previously identified donor israpidly available, wrote the authors. However, since the risk oftreatment-related complications is high, these patients should be managed inhighly specialized centers and transplant approaches aimed at reducing theoccurrence of [GVHD] and transplant-related complications should be prioritized.

Reference

Giardino S, Latour RP, Aljurf M, et al. Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: a retrospective analysis on behalf of EBMT group [published online April 8, 2020]. Am J Hematol. doi: 10.1002/ajh.25810

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Cancer Patients With COVID-19 May Have Higher Risk of Severe Illness and Death – Cancer Health Treatment News

People with cancer who contract the new coronavirus appear to have a greater risk for severe COVID-19 illness and death, but this may depend on their cancer stage and the type of treatment they are receiving, according to recent research. In fact, those with early-stage cancer may fare as well as people who have not had cancer.

Researchers from some of the earliest and hardest hit epicenters of the COVID-19 pandemic described outcomes among cancer patients with the coronavirus (officially known as SARS-CoV-2) during a special session the American Association for Cancer Research (AACR) virtual annual meeting last week. Soon after the conference, another group of researchers published an analysis of mortality among cancer patients in New York City.

Early reports from China, where the pandemic originated in late December, showed that older people, those with compromised immune systems and those with underlying health conditions are more susceptible to severe COVID-19. One study saw a death rate of 6% for people with cancermore than twice as high as the overall estimated COVID-19 mortality rate in China, but lower than the rates seen in people with diabetes (7%) or cardiovascular disease (11%).

Chemotherapy medications and some targeted therapies for cancer can cause neutropenia, a temporary depletion of immune system white blood cells that fight infection. People who receive bone marrow stem cell transplants or CAR-T therapy or for blood cancers typically receive strong chemotherapy to kill off existing blood cells and make room for the new ones. Conversely, immunotherapies such as checkpoint inhibitors and CAR-T therapy unleash natural or engineered T cells to fight cancer, which in some cases can trigger an excessive immune response that leads to harmful inflammation.

Two reports at the AACR meeting provided updates from China. Li Zhang, MD, PhD, of Tongji Medical College described outcomes among 28 cancer patients with COVID-19 in Wuhan, the initial epicenter of the pandemic.

Seven had lung cancer and the remainder had 13 other cancer types. Just over a third had Stage IV, or metastatic, cancer. Nearly 30% acquired the coronavirus at medical facilities. About half had severe disease, 10 patients required mechanical ventilators and eight diedmostly from acute respiratory distress syndromegiving a mortality rate of 29%.

Although three quarters had ever undergone surgery, radiation or chemotherapy, a majority had not received treatment recently. Only one person received radiation, three received chemotherapy, two received targeted therapy and one received immunotherapy within two weeks prior to their COVID-19 diagnosis. Recent cancer treatment was associated with a fourfold increased risk of severe outcomes. However, the single patient treated with a checkpoint inhibitor (for liver cancer) had mild COVID-19 and a short hospital stay.

Similarly, as part of his discussion of immunotherapy for cancer in the COVID-19 era, Paolo Ascierto, MD, of the National Tumor Institute in Naples, noted that just two out of 400 patients on immunotherapy at his institute tested positive for the coronavirus, they were asymptomatic and they recovered quickly, leading him to speculate that immunotherapy might somehow be protective against COVID-19.

Hongbing Cai, MD, of Zhongnan Hospital of Wuhan University, presented data on 105 cancer patients and 536 age-matched people without cancer at 14 hospitals in Hubei province who developed COVID-19. Results were also published in Cancer Discovery. Twenty-two had lung cancer, 13 had gastrointestinal cancers, 11 each had breast cancer and thyroid cancer, nine had blood cancers such as leukemia or lymphomawhich affect white blood cells that carry out immune responsesand six each had cervical and esophageal cancer.

In general, patients with cancer deteriorated more rapidly than those without cancer, Cais team reported. Cancer patients with COVID-19 were nearly three times more likely to have severe or critical illness (34%), be admitted to an intensive care unit ICU (19%) or be put on a ventilator (10%). Whats more, people with cancer were about twice as likely to die as COVID-19 patients without cancer (11% versus 5%, respectively).

People with blood cancers or lung cancer, as well as those with metastatic cancer, had a higher risk of severe events. Two thirds of the blood cancer patients and half of the lung cancer patients had such events. Among the lung cancer patients, 18% were put on ventilators and 18% died. In contrast, no one with breast, thyroid or cervical cancer required ventilators or died.

In particular, those with blood cancersmore than half of whom had severe immune suppressionhad about a 10-fold higher risk of severe events or death. Two thirds had severe symptoms, 22% were put on ventilators and 33% died. These patients all had a rapidly deteriorated clinical course once infected with COVID-19, the researchers wrote.

People with metastatic cancer had about a six-fold higher risk of severe events or death. But people whose cancer had not yet spread were not significantly more likely to have severe events or die than COVID-19 patients without cancer. People currently on cancer treatment and those with a history of cancer who had completed treatment were both at higher risk.

People who underwent surgery within the previous 40 days had higher rates of severe events, ICU admission, ventilator use and death, but this was not the case for those who received only radiation. In this study, unlike Zhangs and Asciertos, people treated with immunotherapy did not fare so well. Four of the six patients who recently received checkpoint inhibitors had critical symptoms and two died.

Based on our analysis, COVID-19 patients with cancer tend to have more severe outcomes when compared to the non-cancer population, the researchers wrote. Although COVID-19 is reported to have a relatively low death rate of 2% to 3% in the general population, patients with cancer and COVID-19 not only have a nearly three-fold increase in the death rate than that of COVID-19 patients without cancer, but also tend to have much higher severity of their illness.

In a related study, Marina Chiara Garassino, MD, of Fondazione IRCCS National Tumor Institute in Milan, presented the first data from the international TERAVOLT registry, which is collecting data about COVID-19 among people with lung cancer and other thoracic malignancies. She noted that TERAVOLT was registering around 70 new cases per week from around the world per week.

This population may be especially vulnerable to COVID-19 due to older age, lung damage, smoking and underlying health conditions, Garassino said. Whats more, the symptoms of COVID-19 overlap with lung cancer, making diagnosis very challenging.

Garassino described results from the first 200 cancer patients with COVID-19 in more than 20 countries. Non-small-cell lung cancer was the most common type, and nearly three quarters had metastatic disease. About 20% received only targeted therapy, 33% received chemotherapy alone and 23% received immunotherapy alone.

A majority (76%) were hospitalized, but most were not offered intensive care for COVID-19; just 9% were admitted to an ICU and 3% were put on ventilators. More than a third (35%) died, mostly due to COVID-19 rather than cancer. Specific types of cancer treatment were not significantly associated with an increased risk of death.

But not all studies have seen worse COVID-19 outcomes among people with cancer. Fabrice Barlesi, MD, PhD, and colleagues looked at 137 COVID-19 patients with cancer at Gustave Roussy, a cancer center near Paris. They had a variety of cancer types, with blood cancers and breast cancer being most common. Nearly 60% had active advanced disease while 40% were in remission or being treated with potentially curative therapy.

Within this group, 25% had worsening COVID-19 after admission, 11% were admitted to the intensive care unit (ICU) and 15% died. Again, people with blood cancers were more likely to have worse outcomes. Treatment with chemotherapy within the past three monthsbut not targeted therapy or immunotherapydoubled the likelihood of worsening disease. But this only applied to people with active or metastatic cancer, not those who had localized disease or were in remission.

The 15% death rate among people with cancer at Gustave Roussy was lower than the 18% rate for all COVID-19 patients in Paris and in France, Barlesi said. His team concluded that both incidence and outcomes of COVID-19 among cancer patients seem to be comparable to the population as a whole. However, people with blood cancers, those treated with chemotherapy and frail patients are at greater risk.

Discussing how to manage cancer patients during the COVID-19 pandemic, Cai recommended self-protective isolation, strict infection control in hospitals and shifting some medical services online.

With regard to cancer treatment, she said, clinicians need to develop individualized plans based on a patients tumor type and stage of disease. She added that postponing surgery, if appropriate, should be considered in areas with current outbreaks. Radiation therapy, she said, could go ahead according to existing treatment plans with intensive protection and surveillance. Whether people with early-stage cancer need to postpone their treatment remains an unanswered question, she said.

Click hereto read the abstracts from the AACR COVID-19 and cancer session.Learn about What People With Cancer Need to Know About the New Coronavirus.

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Italy’s Menarini Group to acquire Stemline Therapeutics for $677M – MedCity News

An Italian pharmaceutical and diagnostics company plans to acquire a New York-based firm with a drug used to treat a rare blood cancer.

Florence, Italy-based Menarini Group said Monday that it would spend up to $677 million to buy Stemline Therapeutics, a biotech company based in New York.

Shares of Stemline were up 153.7% on the Nasdaq by late morning following the news. Menarini is a privately held company.

Stemline won Food and Drug Administration approval in December 2018 for Elzonris (tagraxofusp-erzs), a drug used to treat blastic plasmacytoid dendritic cell neoplasm, or BPDCN, in patients aged 2 and older. BPDCN is a rare and aggressive bone marrow cancer that accounts for less than 1% of all acute leukemias. The standard of care for the disease was previously intensive chemotherapy followed by stem cell transplant, though many patients were unable to tolerate that therapy.

Joining Menarini represents a unique opportunity for Stemline to advance the commercialization of Elzonris across the globe and to accelerate the development of our pipeline of oncology assets, Stemline CEO Ivan Bergstein said in a statement. We have transitioned Stemline over the last several years into an established commercial-stage operation with a novel treatment, a growing pipeline and a strong foundation.

Elzonris targets a cell-surface protein known as CD123, which is expressed in BPDCN as well as other blood cancers like acute myeloid leukemia (AML), chronic myeloid leukemia, B-cell acute lymphoblastic leukemia, Hodgkins lymphoma, some non-Hodgkins lymphomas, hairy cell leukemia, myelodysplastic syndrome and some myeloproliferative disorders (MPNs). The ClinicalTrials.gov database lists other studies in BPDCN that are recruiting or not yet open for enrollment, along with a study in chronic myelomonocytic leukemia and myelofibrosis and completed studies in AML and multiple myeloma.

Other drugs in Stemlines pipeline include SL-701, which targets IL-13Ra2, EphA2 and survivin and is in Phase II development for the brain cancer glioblastoma; and SL-801, a small molecule that targets XPO1 and is in a Phase I clinical trial in patients with solid tumors.

Karyopharm Therapeutics Xpovio (selinexor) also targets XPO1 and has Food and Drug Administration approval for multiple myeloma.

Photo: designer491, Getty Images

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Investigational agents to treat hematologic malignancy in pipeline – Dermatology Times

Researchers are learning more about how to diagnose and better treat blastic plasmacytoid dendritic cell neoplasm, a rare cancer that often presents with skin manifestations, according to a review published March 2020 in Current Opinion in Hematology.1

Blastic plasmacytoid dendritic neoplasm patients have suffered historically poor outcomes. Years ago, doctors were limited to treating these patients primarily with intensive chemotherapy regimens used to treat acute myeloid leukemia or acute lymphoblastic leukemia patients.

But in 2018, the U.S. Food and Drug Administration (FDA) approved tagraxofusp-erzs (Elzonris, Stemline).

Tagraxofusp-erz is the first approved drug indicated specifically for blastic plasmacytoid dendritic neoplasm, and its use is recommended in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.Newer targeted agents to treat the hematologic malignancy are in the pipeline.

Notable changes in recent years

The World Health Organization (WHO) named blastic plasmacytoid dendritic cell neoplasm (BPDCN) and classified it under acute myeloid leukemia and related precursor neoplasms in 2008. Some eight years later, WHO established BPDCN as a distinct entity.

Just how many people have BPDCN isnt clear. But it is thought that there are about 0.04 cases of the cancer per 100,000 people. And about three in four patients are older men.

Derived from plasmacytoid dendritic cells, BPDCN generally is an aggressive disease. It presents clinically on the skin in about nine out of every 10 cases. Skin lesions tend to be asymptomatic, often appearing as bruise-like lesions, plaques or nodules, according to the paper.

While a small percentage of patients will present with skin disease only, most show signs of BPDCN in the bone marrow, lymph nodes or visceral organs. Rarely, patients will have no cutaneous evidence and instead present with the leukemic phase of the cancer. About 30% of patients also have central nervous system involvement.

Flow cytometry to determine the immunophenotype is an essential component of diagnosing [blastic plasmacytoid dendritic cell neoplasm], the author wrote.

CD123, an interleukin-3 receptor alpha, is over expressed in nearly all BPDCN cases. These cancer cells also may be positive for CD4, CD56, CD303 or TCL1, according to the paper.

Some authors have found a recurrent MYC gene rearrangement in these patients. That particular genetic aberration is associated with an older age at diagnosis and worse prognosis.

Treatment is evolving

Unfortunately, doctors have to rely largely on retrospective studies looking at BPDCN treatment options.Those studies suggest that BPDCN, generally, responds better to acute lymphoblastic leukemia regimens compared to acute myeloid leukemia treatment options. However, most responses to these regimens are transient, the author reported.

Retrospective studies suggest allogeneic stem cell transplant for eligible patients in their first remission offer the highest overall survival rates, including 3- and 4-year overall survival rates ranging from 74% to 82%.Tagraxofusp-erzs targets CD123. It consists of recombinant human interleukin-3 fused to a truncated diphtheria toxin, according to the paper.

Binding the drug to CD123 on the cell surface leads to cellular internalization of the diphtheria toxin, which ultimately leads to inhibition of protein synthesis and cell death, the author wrote.

In a phase I/II clinical trial of 44 untreated or relapsed/refractory BPDCN patients, 21 of 29 previously untreated patients achieved complete remission and 13 of those went on to have a stem cell transplant. Overall response rate of the 15 patients with relapsed/refractory BPDCN was 67% with tagraxofusp-erzs, with an average overall survival of 8.5 months.

Eighteen of the 44 patients studied developed the most critical treatment-related adverse event, capillary leak syndrome. Two patients died from capillary leak syndrome during the study.Researchers are studying investigational agents aimed at treating BPDCN. These include IMGN632, a humanized antibody-drug conjugate with an anti-CD123 monoclonal antibody conjugated to a DNA-alkylating payload, the author wrote.

Researchers are evaluating the safety and efficacy of treating CD123-positive malignancies including BPDCN with the monoclonal antibody targeting CD123 and CD3 XmAb14045.

Venetoclax, a BCL-2 inhibitor, is yet another agent in the pipeline for BPDCN patients.

as knowledge is gained on the molecular changes that occur in [blastic plasmacytoid dendritic cell neoplasm], this will ideally lead to more targeted and effective therapies in the years to come, the author wrote.

Disclosures:

Kendra Sweet, MD, has received honoraria from Stemline Therapeutics.

References:

1 Sweet K. Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment. Curr Opin Hematol. 2020;27(2):103-107.

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Investigational agents to treat hematologic malignancy in pipeline - Dermatology Times

AVROBIO to Collaborate with Saladax Biomedical on New High-Speed Diagnostic Assay Used with Busulfan Conditioning to Enable Widespread…

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced a new development and commercialization agreement with Saladax Biomedical, Inc. (Saladax), a leading diagnostics provider focused on developing blood tests for personalized dosing, to develop and validate a fully automated nanoparticle immunoassay kit designed to simplify and streamline therapeutic drug monitoring (TDM) for patients treated with the conditioning agent busulfan.

At AVROBIO, we push ourselves to be at the forefront of technologies advancing lentiviral gene therapy, and its in this spirit that were funding the development of this kit, said Geoff MacKay, AVROBIOs president and CEO. Our personalized conditioning approach is already delivering results. We believe this new assay kit will, for the first time, provide convenient busulfan TDM close to the patient, potentially improving both the patient experience and long-term outcomes, as well as enabling many more hospitals and clinics to become TDM-capable sites.

AVROBIOs state-of-the-art plato gene therapy platform incorporates TDM protocols designed to optimize busulfan dosing over four days, with the goal of maximizing stem cell engraftment while minimizing side effects. TDM evaluates how quickly a patient metabolizes busulfan a rate that can vary significantly from patient to patient and even from one day to the next for the same patient. Current assays that inform that dose adjustment can take hours to return results and must be processed at specialized laboratories with trained staff that may not be geographically convenient to the gene therapy dosing site.

The technology used to deliver these rapid test results is based on an extensive intellectual property portfolio developed by Saladax in the field of TDM. The new assay kit under development by Saladax, which collects a small blood sample, is able to return results on patient metabolization of busulfan in minutes using hospitals standard analytical devices, greatly expanding access to personalized conditioning with busulfan.

Personalized Gene Therapy to Optimize Durable Protein Expression including in Brain, Muscle and Bone

AVROBIOs investigational gene therapies start with collecting the patients own hematopoietic stem cells. In the companys manufacturing process, a lentiviral vector is used to integrate a therapeutic gene designed to produce functional protein essential to cellular health into the patients chromosomes. Prior to dosing, treating clinicians use busulfan, an extensively validated conditioning agent generally considered to be the gold standard for ex vivo lentiviral gene therapy, to create space in the patients bone marrow. Finally, the patient receives the gene therapy and the therapeutic stem cells are expected to engraft in the bone marrow and produce generations of daughter cells, each containing the therapeutic gene. This approach is designed to drive durable production of the functional protein throughout the patients body, including hard-to-reach tissues such as the brain, muscle and bone. A distinguishing feature of this type of gene therapy with busulfan conditioning is that some of the corrected cells are expected to cross the blood-brain barrier and thereby potentially address central nervous system manifestations.

Earlier this year, AVROBIO reported initial clinical results for the first patient conditioned with busulfan using TDM prior to dosing in AVROBIOs Phase 2 clinical trial of its investigational gene therapy, AVR-RD-01, for Fabry disease. The early data from this patient showed increased endogenous enzyme activity at one month following dosing, as compared to other patients in the trial who received a different conditioning agent. Initial data suggest side effects, including nausea, mucositis, fever, rash and hair loss, which were consistent with those expected based on clinical experience of busulfan, developed eight to 10 days after dosing with busulfan and resolved quickly.

About AVROBIO

Our mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato gene therapy platform, our foundation designed to scale gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits of Saladaxs immunoassay kits, including the ability to improve, simplify and streamline therapeutics drug monitoring for patients treated with the conditioning agent busulfan and enable local commercialization of AVROBIOs proprietary platform worldwide, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety profile of our investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that AVROBIO may not realize the intended benefit of Saladaxs immunoassay kits, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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AVROBIO to Collaborate with Saladax Biomedical on New High-Speed Diagnostic Assay Used with Busulfan Conditioning to Enable Widespread...

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COVID-19 Impact On Global Stem Cell Therapy Market 2020 : Key Players, Trends, Share, Industry Size, Growth, Opportunities, Forecast To 2026 - Cole of...