The topic I covered at IACH is stem cell mobilization and novelties in the field of stem cell mobilization. I’ve assessed that in terms of medicinal products used to induce and improve stem cell mobilization, there has been little novelty since the marketing approval for plerixafor more than 10 years ago. So, we pretty much still have the same tools in our toolbox: GCSF, acutely myelosuppressive chemotherapy, and plerixafor as a rescue for patients who behave as poor mobilizers to induce and improve stem cell mobilization...
The topic I covered at IACH is stem cell mobilization and novelties in the field of stem cell mobilization. I’ve assessed that in terms of medicinal products used to induce and improve stem cell mobilization, there has been little novelty since the marketing approval for plerixafor more than 10 years ago. So, we pretty much still have the same tools in our toolbox: GCSF, acutely myelosuppressive chemotherapy, and plerixafor as a rescue for patients who behave as poor mobilizers to induce and improve stem cell mobilization.
So, stem cell mobilization and collection is used both in the autologous setting, mostly for autologous cell transplantation that is being used as a supportive care for high dose chemotherapy. And in more rare instances, autologous peripheral blood CD44-positive cells will be collected in view of manufacturing of some innovative gene therapies. Stem cell mobilization is also used for healthy donors in view of allogeneic hematopoietic stem cell transplantation, whether donors are related or unrelated to the recipient.
In donors, obviously we cannot use chemotherapy. That’s an obvious statement. We cannot use, theoretically, plerixafor since the marketing approval for this drug does not include healthy donors. However, and recently, there has been several reports of the use of plerixafor either in the context of clinical trials or on the basis of compassionate use, if I can say so. And in particular, I guess, during the COVID-19 pandemic we faced some difficult situations where dealing with poor mobilizers the usual way was not possible and plerixafor was introduced to improve mobilization in healthy donors.
What we learned from this experience is basically that it works. It works in healthy donors as it works in patients, candidates for autologous transplantation. It is safe for donors and it appears to be safe in recipients with apparently no increase in GvHD. But again, let’s remain cautious. No marketing approval in the context of healthy donor mobilization. So, in principle, use it in the context of clinical trials or use it in exceptional and documented circumstances where no other option is available.
In autologous patients, we already know a lot about the introduction of plerixafor. On time introduction based on immediate counts of CD44-positive cells, circulating CD44-positive cells immediately prior to the planned. And in case this figure is quite low, usually below 10 or 15 per microliter, although the marketing approval allows for up to 20. But then, you can introduce plerixafor on rescue most patients. The availability of these drugs has made mobilization failures quite exceptional. We still face a few patients, but very few cannot be collected. So, not having a graft has became a rather rare instance in which we cannot offer high-dose chemotherapy supported with autologous transplantation in patients.
To conclude this comment and presentation, there are obviously many agents that mobilize stem cells and that has been proven in preclinical models using these individual assay or animal assays. Some of these drugs have moved to early phase clinical trials, Phase I or Phase II, but none of them has reached the market, and probably one of the reasons that this is a niche market, if I can say so, relatively small number of patients and it’s expected to decrease significantly in the near future as the new generation of cellular therapies come to the market and may replace autologous transplantation in some instances.
So, no new drug to optimally mobilize and collect patients and donors and anticipation is key, and taking advantage of all the existing technologies for apheresis including somewhat improved cell processors, optimizing the parameters of the procedure allows to collect properly most of the candidate patients and candidate donors for collection.
