Medical progress this week
9 - 15 June
Here are my picks for the most important advances in medicine this week.
1. Improving leukemia treatment
Chronic lymphocytic leukemia (CLL) is a B cell cancer partially driven by a tyrosine kinase, BTK, and an anti-apoptotic protein, BCL-2.
This phase 3 trial tests a combination of a BTK inhibitor (Ibrutinib) and a BCL-2 inhibitor (Venetoclax).
Ibrutinib-Venetoclax improved progression-free and overall survival vs. previous standards of care.
Ibrutinib causes cardiovascular off-target effects in some patients, so cardio-safer versions are now being tested - and already have approval (with Venetoclax) in some countries.
https://nejm.org/doi/full/10.1056/NEJMoa2504341
2. Long-term follow-up for a haemophilia B gene therapy
Haemophilia B causes bleeding due to deficiency in clotting factor IX - it usually affects males.
This is a therapy that delivers a functional copy of the factor IX gene to the liver via an adeno-associated virus (AAV).
There's only 10 patients but, with a follow-up of 12 years, patients had fewer bleeds and most no longer needed factor IX infusions.
It was safe, too - there was no increased clotting risk or chronic liver disease.
This gene therapy used a wildtype factor IX, but newer therapies use a variant of factor IX that's more active - so the outcomes might get better yet.
https://nejm.org/doi/full/10.1056/NEJMoa2414783
3. An answer to an age-old question
Which is the better fluid for hospitalized patients: normal saline or Ringer’s lactate (Hartmann’s)?
This is the first hospital-wide trial to test the question: the stock fluid in hospitals was the intervention.
It’s a massive cluster-randomized trial, with 7 hospitals and 43,626 patients.
There was a trend towards Ringer’s lactate - but no significant difference (in 90-day death/readmission).
The main limitations are that the trial wasn’t powered to detect small differences, that there’s no data on biochemistry (e.g. hyperchloremic acidosis), and that adherence to assigned fluid wasn't 100%.
https://nejm.org/doi/full/10.1056/NEJMoa2416761
4. Approval of a new ROS1 inhibitor for lung cancer
~1–3 % of non-small cell lung cancers are driven by a fusion of the ROS1 tyrosine kinase that activates it continuously - this usually affects younger patients and never-smokers.
These are two pooled single-arm, phase 2 trials that tested Taletrectinib, a ROS1-selective, brain-penetrant tyrosine kinase inhibitor, and led to its FDA-approval this week.
It was more effective against ROS1 mutants and brain metastases than some previous ROS1 inhibitors, with a gentler neurologic safety profile.
Ongoing head-to-head trials vs. earlier-generation ROS1 inhibitors will determine whether taletrectinib becomes the first-line standard.
https://ascopubs.org/doi/pdf/10.1200/JCO-25-00275
5. Towards fluent speech with brain implants
Conditions like motor neuron disease can cause loss of speech.
Early devices aim to restore this speech by reading and decoding the signals from speech-producing neurons and converting them to speech - via a computer.
This new device has lower latency than previous methods, restores the rhythm of speech, allows emphasis on individual words - and even singing.
It’s still slower and less clear than natural speech, and it’s an invasive approach that requires neurosurgery, but, with further improvements, this could help restore speech to patients who've lost it due to conditions like motor neuron disease.