Blood cancer cures aren’t here yet — but incremental combinations bring the field closer

A conference like the annual meeting of the American Society of Hematology, which concluded last week, is home to the most cutting-edge advances in treatments for blood diseases. And while game-changing studies are certainly a big part of the narrative, scientists following the field’s progress look to small, incremental successes and drug combinations to drive the future of treatment for the direst patients.

“This year was a sort of maturation of incremental advances,” said Lee Greenberger, chief scientific officer of the Leukemia and Lymphoma Society. “What you’re seeing is improvements in something like progression-free survival, but we’re not really curing people — and the question is, can we cure people with these therapies, and what is holding them back?”

One of the limitations is the sheer complexity of the microenvironment for tumor cells in the blood, presenting so many targets that may or may not work for different patients. In the future of blood cancer, combination therapies that attack multiple targets or spur the immune system to take action will likely be the way to reach a cure, Greenberger said.

As we look back at the advances both large and small from a week of scientific indulgence, these potential combinations are what stand out as a means to change the course of blood cancer down the road.

A blockbuster gets some help

For pharma giant Merck & Co., drug combinations are a particular area of expertise due to the not-so-secret weapon that is the blockbuster cancer drug Keytruda. A standard of care in dozens of different types of tumors, the immunotherapy turns off the switch that keeps the patient’s body from fighting off deadly disease.

And in results presented at the conference, Keytruda got a helping hand from favezelimab, a cancer treatment that also turns off cancer’s ability to hide from the immune system but via a different switch called LAG-3. The one-two punch was able to give patients with classic Hodgkin lymphoma a more robust response in a phase 1/2 trial.

Drug combinations are often a trial proposition — putting together a mainstay like Keytruda and a newer drug like favezelimab, for instance, gives each treatment a better shot at getting the job done, said Gregory Lubiniecki, vice president of oncology clinical research at Merck.

“We have been fortunate that (Keytruda) ended up having such a prominent role in reinvigorating the immune system and the immune response against tumors — I don’t know that anyone necessarily would have predicted that the PD-1/PD-L1 axis had such a prominent role,” Lubiniecki said. “We’re still conducting a number of experiments with TIGIT and LAG-3 to determine how prominent a role they play together in reinvigorating the immune system to attack tumors.”

And with so much still unknown about the myriad diseases that comprise blood cancers, a trial is the only way to understand just how they might work. For a big company like Merck, the number of opportunities available — even incrementally — can add to the cadre of treatments available for patients.

“The benefit of having such a broad pipeline will be that we’re able to explore the activity of these agents where they’re primarily designed for benefit, and secondly to easily combine agents in certain tumors where they might have activity,” Lubiniecki said. “I certainly look forward to seeing how treatment of B cell malignancies such as non-Hodgkin’s lymphoma or chronic lymphocytic leukemia have progressed as there are many agents and mechanisms of action that are being explored.”

Lubiniecki pointed out that data showing a successful treatment doesn’t develop overnight, and that a series of incremental successes are what lead to better outcomes for patients.

New targets, together

Companies smaller than Merck also have their hands in developing important treatments for blood cancers that could be combined with standards of care, including one called an MLL-menin inhibitor that the LLS’s Greenberger said is particularly exciting for the field.