In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.
In, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.
The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.
In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.
In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.
“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.
Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase IIIresults, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.
In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.
Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”
Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.
With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.
The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.
This year’s late-breaking abstracts at ASH are:
Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.
Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.
Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.
Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).
Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.
A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study