Practice-Changing Data at This Year's ASH Meeting

Roxanne Nelson, RN, BSN

November 30, 2020

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: December 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH's Committee on Communications.

Ruxolitinib in Chronic GvHD

"One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception," said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is "almost certainly a practice changer," he said, is the REACH 3 study (abstract 77) of the JAK-inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

"This has been really hard to treat in patients undergoing allogeneic bone marrow transplants," said Brodsky. "Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don't work that well."

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. 

The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

"This is the first successful phase 3 trial for chronic GvHD," Brodsky commented.  

Transplants for Older Patients With MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It's clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. "The thinking is that bone marrow transplant would be too toxic in this age group," he said. "But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage — 48% versus 27% at 3 years for transplantation — and it was seen across all subgroups."

Subcutaneous Daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

"From previous years we've learned that daratumumab has had a major impact on outcomes in multiple myeloma," said Brodsky. "The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era."  

Negative Data With Tranexamic Acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

"They found absolutely no difference in bleeding or need for transfusion," said Brodsky. "What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia."

'Very Exciting' News About Gene Therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are "very, very exciting," he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy comprised of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. "About 40% of patients have naturally occurring antibodies to AAV5 and they have been excluded from previous trials because it was thought they wouldn't take the vector," said Brodsky. "But only one patient didn't get a response."

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild-to-normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

"This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia," said Brodsky. However, he added that "we will still need to see more patients and have longer follow-up."

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on "off-the-shelf" products is underway. This topic will be explored during the presidential symposium, entitled, "Universal Donor Solutions in Hematology."

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

"We were very impressed with the magnitude of the responses, and also the durability," said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, Massachusetts, in a press release. "I was also struck early on by how favorable the safety profile was compared to what we've been seeing in the fast-growing lymphomas, such as large B cell lymphoma."

Race and Bloods Cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that "self-reported race was the best indicator of survival," noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, "so there was no effect of different treatment, since they were on therapy determined by the trial," said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Thus, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on December 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist's side, she explained, and address questions such as: "What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?" 

COVID-19 and Blood Disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. "This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection," say the authors.

"We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don't have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots," said Lee.

"More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials."

'Fireside Chat' With Fauci

COVID-19 will be on the agenda for a special session billed as a "fireside chat" with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

"This will be kicking off our meeting on Saturday morning," said Lee.

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