ORLANDO, Fla. – The world’s biggest and certainly most lavish hematology gathering, the 61st American Society of Hematology conference, just ended in Orlando, having brought 30,024 people from 25 countries to glory in Florida sunshine, if they got outside, but mostly to bask in the discipline’s most up-to-the-minute data.  

The amount of research was staggering, with 5,978 abstracts available for review. Key themes included work aimed at overcoming obstacles to CAR T therapy, new progress in preventing and treating venous thromboembolism, moves to address health care disparities and new developments in the care of sickle cell diseases. Late-breakers highlighted new data on Blincyto (blinatumomab, Amgen Inc.), Sanofi SA's sutimlimab, azacitidine and Darzalex (daratumumab, Janssen Biotech Inc.). 

But it was the new findings on CAR T therapies and alternatives to that modality that dominated, alongside ongoing research into the fast-developing field of gene therapy.  

At Sunday’s scientific session on gene editing, Wendell Lim, professor and chair of cellular and molecular pharmacology at the University of California, San Francisco, and the co-founder of Cell Design Labs, discussed his laboratory’s work to use gene editing to improve cell therapies, in particular CAR T cells. To fully capitalize on their strengths, he said, cell therapies will need to be both safer and more powerful – a combination that is inherently challenging. Lim’s synNotch technology addresses that challenge by editing cells to contain multiple sensors, whose combined input controls the “common currency” of gene expression output. The combinatorial possibilities result in a CAR T cell that reacts to its target antigen only when it senses that it is in a tumor microenvironment, which could eliminate off-target activity. 

CAR T cells have proved to be a major advance in treating patients with refractory B-cell malignancies so far. But, often, in approaching those issues, "we solve one and we create another," Stephen Schuster, a doctor at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, said Saturday. Two new CAR T agents targeting CD19 have been approved in the last two years. A third of patients' lymphomas respond to at least one of the two. "However, the two-thirds of patients who don't respond to CAR T-cell therapy are now our new unmet need," he said. 

On Saturday, new phase I/II data from Autolus Therapeutics plc showed that AUTO-3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, was well-tolerated in a phase I/II study. The clinical trial, Alexander, is in patients with relapsed/refractory diffuse large B-cell lymphoma and pediatric acute lymphoblastic leukemia (ALL). The new, preliminary data show 90% of patients had a complete response and 100% had overall survival at 12 months in CAR T-naïve pediatric ALL patients. 

Often less eye-catching, but no less important, were studies that can make both the cells themselves and transplantation procedures safe enough for much wider use of cell and gene therapies. On Tuesday, researchers from Boston Children’s Hospital reported that three adult patients who had received an autologous transplant of gene-edited hematopoietic stem cells lacking BCL11A produced high levels of functional hemoglobin and had reduced disease symptoms for at least eight months after transplantation.  

Two preclinical presentations could pave the way for using hematopoietic stem cell transplants in patients who are currently too sick to tolerate the procedure, as well as in indications where its toxicities preclude its use. Researchers from the NIH presented a primate case study demonstrating that they were able to forego chemotherapy and radiation but still achieve rapid engraftment of hematopoietic stem cells after bone marrow conditioning with Magenta Therapeutics Inc.’s experimental antibody-drug conjugate, CD117-ADC. Also, Forty Seven Inc. reported that a combination of its c-KIT (CD117)-targeting antibody, FSI-174, and its macrophage checkpoint blocker, magrolimab (5F9), could deplete stem cells by inducing phagocytosis. In primates, combination treatment, but not FSI-174 alone, depleted stem cells from the bone marrow.  

In an effort to get sickle cell disease researchers, drug developers, patients and regulators all on the same page, on Saturday ASH and the FDA released new recommendations aimed at establishing uniform global standards for clinical trial endpoints to evaluate new therapies. It's "the first-ever comprehensive look at what endpoints we have knowledge and evidence around and where there still needs to be some research," Julie Panepinto, a professor of pediatric hematology at the Medical College of Wisconsin, told BioWorld. Panepinto is co-chair of ASH’s Guideline Oversight Committee. The hope, she said, is to promote more disease-modifying therapies for sickle cell disease. 

New research on sutimlimab, an investigational complement pathway inhibitor under development by Sanofi SA's Bioverativ unit, was presented and showed substantial benefits for people with the rare autoimmune disorder cold agglutinin disease (CAD). In a phase III trial called Cardinal, people with CAD receiving the drug for 26 weeks had improved hemoglobin levels, required fewer blood transfusions and felt significantly less fatigued, according to new data from a session on late-breaking research. 

Kura Oncology Inc., encouraged by new data on tipifarnib and positive feedback from the FDA, said Sunday that next year it will initiate a single-arm, phase II registration-directed trial of the candidate in angioimmunoblastic T-cell lymphoma, a rare and often aggressive form of peripheral T-cell lymphoma. As designed, the trial could support an NDA seeking accelerated approval, the San Diego-based company said. 

Preliminary data from a phase II test of Constellation Pharmaceuticals Inc.'s CPI-0610 in patients with myelofibrosis, previewed to market adulation in November, got a full airing Monday. Updated data from the trial, called Manifest, showed that at 12 weeks, 12 out of 15 evaluable JAK inhibitor-naïve patients treated with a combination of CPI-0610 and Jakafi (ruxolitinib, Incyte Corp.) had at least a 35% reduction in spleen volume. Investigators also saw evidence of activity in ruxolitinib-resistant or -intolerant patients. 

Janssen Biotech Inc. released upbeat follow-up survivability data on Imbruvica (ibrutinib) from two studies and an integrated analysis evaluating Imbruvica in previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The 48-month follow-up analysis of the phase III E1912 study reported a statistically significant difference in progression-free survival and overall survival for Imbruvica plus rituximab compared to a standard chemoimmunotherapy regimen of fludarabine, cyclophosphamide and rituximab.  

On Monday, the Janssen Pharmaceutical Cos. of Johnson & Johnson released phase III data showing that adding Darzalex (daratumumab) to carfilzomib (Kyprolis from Amgen Inc.) and dexamethasone (DKd), compared to carfilzomib and dexamethasone (Kd) alone, significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma. 

While disparities remain in putting minority and older patients into clinical trials and being treated for blood cancers, there are successes in getting once-ignored patients into the mix so they can receive the same treatments as others. New data presented Saturday showed that while advances are being made to reach those groups with often unmet needs, there are still improvements that can be made.   

For a quick reference guide to BioWorld’s ASH conference data, here is a listing for Dec. 9, Dec. 10 and Dec. 11

The annual conference had its highest attendance ever this year, with the most coming from the U.S., followed by the U.K., Canada, Germany, China, Japan, France and Switzerland. Roughly 40% of attendees come from outside the U.S. 

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