Recent Breakthroughs in Blood Diseases Advance Myeloma and DOAC Therapies

New research shows promise in improving outcomes for patients with myeloma and in helping physicians better identify patients who need anticoagulation drug reversal therapy. 

The studies, involving physicians from UT Southwestern Medical Center and its Harold C. Simmons Comprehensive Cancer Center, will be presented at the American Society of Hematology (ASH) Annual Meeting & Exposition, Dec. 7–10, in Orlando, Florida. 

Advancing myeloma therapy options

Larry Anderson Jr., M.D., Ph.D., is an Associate Professor in UT Southwestern’s Department of Internal Medicine, Division of Hematology/Oncology. He is an author of two multi-institutional, pharma-led studies related to myeloma that will be presented during the poster session at the ASH Annual Meeting.

“The landscape of myeloma therapy is rapidly advancing, and clinical trials at UT Southwestern are helping to advance the field,” Dr. Anderson says. “If we can move the needle forward and add immunotherapy up front, we can see if we can get better, longer-lasting remissions.”

The phase 2 GRIFFIN study found that adding Darzalex® (daratumumab) to bortezomib, lenalidomide, and dexamethasone in front-line therapy brought on higher response rates in myeloma patients, compared with patients who did not receive Darzalex.

“So far, the data shows a higher percentage of patients are in remission, and the ones in remission are in significantly deeper remissions called molecular remissions.” Dr. Anderson says “It’s too early to know if they will live longer, but so far the responses are better when adding this therapy to standard treatments.”

The phase 3 OPTIMISMM study found that myeloma patients who added pomalidomide to bortezomib and low-dose dexamethasone did better in long-term follow-up than patients who had only bortezomib and dexamethasone therapy.

“We participated in these trials at UT Southwestern, so we have patients seeing benefits from these therapies,” Dr. Anderson says. “They are still coming in every month getting treatments.”

Tests for monitoring direct-acting oral anticoagulants

Ravi Sarode, M.D., is a Professor of Pathology and Internal Medicine (Hematology/Oncology), Chief of Pathology, and the Medical Director of Clinical Laboratory Services at UT Southwestern. At the ASH Annual Meeting, he will chair the education session on direct-acting oral anticoagulants (DOACs) in real life and give a presentation entitled “DOAC monitoring: What tests are available to guide us?”

Dr. Sarode explains that new oral anticoagulants are replacing the traditional, familiar anticoagulant warfarin in patients being treated for thromboembolism. “Warfarin needs to be monitored on a regular basis,” he says. “That’s because warfarin has a relatively high risk of bleeding.” 

These new oral anticoagulants have a much lower risk of bleeding, but there is still risk, Dr. Sarode notes. Patients who develop bleeding need access to a lab test that can determine their level of oral anticoagulant so doctors can decide if reversal treatment is appropriate. 

“It’s possible to assess whether there’s a significant enough amount of the drug in a patient’s blood to give a reversal agent or not,” Dr. Sarode says. He adds that it’s important to appropriately administer these reversal agents, such as andexanet, for three reasons:

1. It’s expensive ­– about $26,000 for a low dose and $52,000 for a high dose.
   
2. It could cause a clotting tendency in a patient who doesn’t need a reversal agent. “That’s the risk-benefit ratio we have to assess,” Dr. Sarode says. “We have to be cautious.”
   
3. They are new. “It’s a very new drug, and we don’t know much about it,” he says. 

“We have to have rapid assays available to guide us in using reversal agents appropriately to prevent harm and reduce costs,” Dr. Sarode says. “We need to be judicious about using it indiscriminately.”

Compared with Warfarin, which has a half-life of three to five days, the new oral anticoagulants have much shorter half-lives. “In the next few hours [after a patient presents], drug levels will be significantly lower, so should we be using these expensive reversal agents?” Dr. Sarode asks.

His talk will focus on the fact that tests are now available to assess the level of oral anticoagulant. “Within about 30 minutes you can know whether a patient needs a reversal agent or not,” he says. 

Most U.S. labs are reluctant to provide the tests. Dr. Sarode says that with tests costing only $500 to $1,000 per year, it makes sense to provide them. Sparing just three patients from a reversal agent could save at least $75,000, he adds. He stresses that a universal assay is needed that can assess effects of many commonly used anticoagulants.