ESH CML/MPN 2025 | Updates in the management of CMML: a case-based presentation

I gave a case-based presentation where I chose two real-world cases from my own clinical practice, both of them were selected because they allowed me to showcase some of the newer developments and some of the current treatment algorithms in CMML, so I used them as a framework for that. 

The first case was of a relatively younger patient, a 63-year-old gentleman, who had higher risk CMML with some high-risk mutations and a blast count of 10%, a fit guy. This allowed me to discuss the current role of transplant, particularly in CMML, and discuss various aspects of that, including some of the more recent publications and guidelines. So some of the sort of key messages of that were some recent retrospective data, large 1,000-plus patient studies from international registries that have shown that transplanting CMML, certainly for lower-risk patients, is not recommended. And even amongst higher-risk patients, the results were still rather circumspect. The take-home message of that particular study that I discussed was that if you’re higher risk disease, according to some of the prognostic scoring systems, if you live for two years after your transplant, then you’re going to do much better with a transplant. But if not, then you would have been better off not being transplanted, which is a bit of a conundrum. And so it’s still quite challenging to know which patients to select. 

I went on to discuss some recent expert consensus guidelines published last year. And a couple of the interesting messages from that set of recommendations are that, whereas we have traditionally given induction treatment, whether it be chemotherapy or hypomethylating agents beforehand in CMML, probably because of the age and the comorbidities of these patients, very often they have real difficulties with that treatment. And so many patients don’t make it to transplant. And so actually the recommendations are to try and take people to transplant as quickly as possible if you’re going to transplant them, which is a bit of a departure from previous, especially as they recommend doing so irrespective of blast count. My case was quite a good one to showcase that because it was a case that didn’t go well. It was an example of this very fit gentleman who we did give chemotherapy to, and he had a torrid course, a very prolonged aplasia, multiple infections, fungal infection, liver and kidney failure, and ultimately was unable to go and proceed with the transplant and sadly died four or five months after being admitted for treatment. So I think it was a useful showcase as to sort of why those recommendations are out there. 

So that was the first case. It also allowed me to discuss a little more about the latest prognostic scoring systems. A headline that I think is worth mentioning was some data from ASH last year, which showed that the IPSS molecular, designed for MDS not CMML, but the outcome of that study was that it was as good, if not perhaps slightly better in CMML than the CPSS mol scoring system. I think the jury is still out on that, but I think that’s interesting as it certainly includes more molecular information. And it also allowed me to discuss the latest classification changes from 2022, notably that the monocyte threshold has been reduced from 1 to 0.5, which many viewers will be aware of. There was another study at ASH that I discussed that actually looked back at a large database of MDS and CMML patients and showed that as many as 25% of MDS patients would now technically fall into the CMML diagnostic category, significantly increasing the frequency of the disease. So that was the first case. 

The second case was slightly different. An older patient, 75, with some modest comorbidities but generally fit, who had proliferative type CMML, not a transplant candidate. So again, we discussed the risk scoring of this patient, but transplant not being an option, it allowed me to then introduce the current management algorithm for these patients, whereby the standard of care for proliferative CMML in most countries would still be considered hydroxycarbamide, and the importance of clinical trials. 

So I introduced the AMMO clinical trial, which is one that we’ve been running in the UK. It’s a Phase II study comparing a novel oral hypomethylating agent, ASTX727, which is now FDA-licensed, FDA-approved, and widely used in the US, not available in the UK. It’s comparing that against best supportive care with or without hydroxycarbamide. The trial recruited extremely well. We completed recruitment of 77 patients seven months ahead of schedule, which I think shows the appetite for trials amongst these patients, and we’re hoping to get the results in May. Now, this patient I presented was someone who went on the study, and I explained how well she did. She had a dramatic response. Her white count, which had been shooting up, returned to normal very quickly. Her renal function, which was deranged, also normalized, which allowed me to discuss some of the ways in which CMML causes renal dysfunction, and that can resolve with successful treatment. She stopped needing blood transfusions, and her quality of life massively improved. She hasn’t spent a day in hospital through 17 cycles of treatment. And then I finished really by going on a whistle-stop tour through some of the newer treatments and trials that are coming along for this disease.

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