Insight

Vincent Rajkumar: Great post by David Steensma highlighting the difficulties of treating neoplastic conditions

Collage photo of Vincent Rajkumar and David Steensma

Jun 20, 2025, 05:57

Vincent Rajkumar: Great post by David Steensma highlighting the difficulties of treating neoplastic conditions

Vincent Rajkumar, Professor of Medicine at the Mayo Clinic in Rochester, Minnesota, and Chair for the Mayo Clinic, shared a post by David Steensma, Chief Medical Officer at Ajax Therapeutics, adding:

“Great post by David Steensma highlighting the difficulties of treating neoplastic conditions. When a trial is “negative” it’s not the fault of the drug, the trial design, the investigators, or patients.

Some cancers and pre cancers are just inherently hard to tackle: biologically hard to eradicate, or difficult to target safely without affecting other normal cells, or the neoplastic cells find a way around our treatments, or their survival mechanisms are just so strong or evolutionarily preserved that they can overwhelm anything we throw at them. Eventually we will find a solution. But it’s a long and hard struggle.”

Quoting David Steensma‘s post:

“With the disappointing announcement today by AbbVie of the negative result of the VERONA venetoclax/azacitidine trial, that brings the tally to (by my count) 17 consecutive negative randomized drug trials in higher-risk MDSsm. This is a slide I made summarizing them.

Vincent Rajkumar

Here is the press release about the VERONA result. I imagine more detailed information will be presented at an upcoming medical conference.

There are many reasons why MDS has been an area with multiple trial failures. Patients tend to be older, often frail and with comorbidities, and with limited access to trials. Pre-clinical models have poorly predicted clinical behavior. Difficult targets (eg TP53) are common. Approaches like immune checkpoint inhibition that work well in other disease settings have not been successful in MDS. Targets like mutant IDH for which there are effective therapies are uncommon in MDS. Too many trials have taken similar approaches (eg HDAC inhibitors.)

There are few biomarkers of early response (or lack thereof) in MDS. Our understanding of disease biology has improved greatly since 2005 but is still incomplete. Response criteria may have focused on the wrong priorities. Management of cytopenias is not standardized. Some trial designs have been flawed. Investigational agents have moved from small phase 1 datasets to large randomized trials quickly, perhaps too quickly. There’s just been some bad luck.

I could go on – there are many other factors contributing to higher-risk MDS being such a “long row to hoe”. It’s just really frustrating. I hope there will be genuine progress for patients soon.”