Question Relevant to All Oncologists Answered at ASH 2017

Zosia Chustecka

November 30, 2017

A big question relevant to all oncologists that will be answered at the forthcoming American Society of Hematology (ASH) 2017 Annual Meeting concerns the use of newer oral anticoagulants instead of older injectable agents for cancer patients with venous thromboembolism (VTE).

The newer oral drugs have been available for some time, but "hematologists and oncologists have been reluctant to use them in cancer patients, until we have trials done in cancer patients," commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and oncology and the director of the Division of Hematology at Johns Hopkins School of Medicine in Baltimore, Maryland.

Well, data from clinical trials conducted specifically in cancer patients are now going to be presented.

One set of results comes from the large international Hokusai VTE Cancer Study (abstract LBA-6), which investigated the use of the oral agent edoxaban (Savaysa, Daichi Sankyo Inc). Another set of results come from a smaller British study, Select D (abstract 625) which investigated the use of rivaroxaban (Xarelto, Janssen).

In both studies, the oral agents were found to be similar to dalteparin (Fragmin, Pfizer), a low-molecular-weight heparin product that is administered subcutaneously. It is considered standard of care for the extended treatment and prevention of recurrence of acute venous thrombosis (VTE) in cancer patients.

These new results are "showing that oral anticoagulants are safe to use in patients with cancer, and this is big news," Dr Brodsky told journalists listening into a meeting preview.

The ASH meeting will take place in Atlanta, Georgia, from December 8-12 and will feature more than 4500 abstracts, of which 1000 will be presented at oral sessions. Many of the others will be presented as posters.

"It is by far the largest hematology conference on the planet," commented Joseph Mikhael, MD, professor of medicine at Mayo Clinic in Phoenix, Arizona. Dr Mikhael is also deputy director of the Mayo Clinic Cancer Center and is chair of the ASH Committee on Communications. More than 25,000 attendees from around the world are expected.

Practice-Changing Results

Several presentations may result in treatment changes, the experts said.

One such presentation will feature the first results from the MURANO trial (abstract LBA-2), which involved patients with relapsed/refractory chronic lymphocytic leukemia. Standard treatment for this patient population is the chemo/immuno combination of bendamuustine plus rituximab, but these new results ― from the first preplanned interim analysis ― show superior outcomes with a newcomer. The oral agent venetoclax (Venclexta, AbbVie and Genentech) showed a "profound improvement" in progression-free survival (PFS), the authors report. It also beat the standard of care on every other clinical outcome. This new drug "represents an advance in treatment," commented Dr Mikhael.

Another potential practice-changing presentation concerns multiple myeloma, with results from the ALCYONE trial (abstract LBA-4). The patients in this trial, who were not eligible for a transplant, were treated with the triplet of bortezomib (Velcade, Millennium), melphalan, and prednisone (VMP), but half of the patients also received the new monoclonal antibody daratumumab (Darzalex, Janssen). The addition of this novel drug to the triplet doubled PFS. The results were driven by the fact that more patients achieved deep responses, the authors report. The four-drug regimen, as used in this trial, is a potential new standard of care, said Dr Mikhael.

More Details on CAR T-Cell Therapy

"Very promising data" will be presented for the novel products with chimeric antigen receptor (CAR) T cells, commented 2017 ASH President Kenneth C. Anderson, MD, of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts.

Two of these agents have been approved in the past year ― tisagenlecleucel-T (Kymriah, Novartis), which is approved for use in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) was approved in August 2017, and axicabtagene ciloleucel (Yescarta, Kite Pharma) was approved in October 2017 for patients with relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The new long-term data come from two large international trials ― the ZUMA trial of axicabtagene ciloleucel in refractory/relapsed NHL (abstract 578) and the JULIET trial of tisagenlecleucel-T in patients with refractory/relapsed diffuse large B cell lymphoma (abstract 577 ). The updated results from these trials show complete responses in patients who had no other therapeutic options. "These are remarkable data...and they show that novel therapies can be used in the real world," Dr Anderson commented.

New Targeted Agents

Two new targeted agents will make their debut at the meeting.

Mogamulizumab is a monoclonal antibody directed against chemokine receptor 4, which is overexpressed on malignant T cells. Meeting attendees will hear about the first phase 3 trial conducted specifically in patients with cutaneous T-cell lymphoma (CTCL), a rare form of NHL that causes intractable itching and leaves patients prone to infections. Results from this trial, known as MAVORIC (abstract 817), show that mogamulizumab is a valuable new therapeutic option for these patients, say the trialists.

The other new agent, BLU-285, has shown considerable clinical activity in patients with advanced systemic mastocytosis, which are a group of mast cell neoplasms that are associated with poor prognosis. This drug was designed as a highly potent and highly specific oral inhibitor of KIT activation loop mutants, including D816V, and KIT D816V is a key oncogenic driver in these cancers. Although the results come from a small phase 1 study (abstract 2), this drug showed marked clinical efficacy, and it targets a known defect, commented Dr Brodsky. "This is so exciting, as it is reminiscent of the Gleevec [imatinib] story in chronic myeloid leukemia from 20 years ago," he said.

For patients with acquired or immune-mediated thrombotic thrombocytopenic purpura (aTTP), a new drug, caplacizumab, looks to be a "potential game changer," said Dr Brodsky. The results with this new drug come from the placebo-controlled phase 3 Hercules study (abstract LBA-1), which show that it achieved a highly clinically meaningful reduction in aTTP-related death and recurrence of aTTP or a major thromboembolic event during study drug treatment, the authors report. They conclude that caplacizumab, which is under development by Ablynx, represents a novel treatment option for patients with aTTP.

Another abstract to look out for, he said, shows further clinical data with emicizumab (Hemlibra, Roche) in pediatric patients with hemophilia A who have developed inhibitors. This agent was recently approved in the United States on the basis of results from the HAVEN-1 and HAVEN-2 trials. It has "been a game changer" for this patient population, Dr Brodsky commented. Now results from HAVEN-2 (abstract 85), which included 57 pediatric patients and is the largest such study to date, show that emicizumab prevented or substantially reduced bleeding episodes and was well tolerated.

Also for hemophilia A patients, there are results from early research on a gene therapy (abstract 650) that is "very exciting," commented Dr Brodsky, because it offers "a potential cure," he said.

Details on all these presentations at the ASH meeting will be reported by a team of medical journalists heading to Atlanta, so check back to read the news as it breaks.

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