EBMT 2026 | Optimizing the gene therapy journey in SCD and thalassemia using learnings from clinical experience

This is a really exciting time in the area where we provide transformative care for patients with sickle cell and thalassemia. But now going beyond just the clinical trial to real-world evidence, I wanted to share the lessons we learned at Cleveland Clinic with the rest of the community where they are starting a new program for gene therapy. So in my talk, I provided lessons from different aspects and phases of therapy. 

First, it is selection. I think this is really important to be able to partner with the classical hematology team. They’re hematologists who provided care for this patient for many years or decades, their social work, their RN. So what we learned at Cleveland Clinic, we did a monthly committee, not only a BMT physician, but also the hematology team, so we can discuss the patients, select them based on their morbidities, but also their psychosocial. And that was really helpful for us to sign in and also sign out because we want this patient to go back to their primary team. Number two within the selection, is the chronic pain. It is many of the adult patients with sickle cells specifically, they suffer from chronic pain. And we initially were restrictive and we were not allowing patients to have more than 10 pain admissions per year, but then we felt patients who may have vascular necrosis, why we are not trying to treat them? So we added a layer of psychosocial assessment to enable us to really detect if any patient has any mental health disorder that could contribute to the chronic pain and help us select patients who could benefit from this. 

In the second phase, which is the stem cell mobilization and collection – this is critical. We learned, because I think in real world, we don’t have the optimum patients that they may be in real world. So instead of the average being or the mean two cycles, we are seeing actually three cycles or more as the mean number of cycles for stem cell collection. So critical is to set up the expectation for patients that they may take up to six cycles. And also, maybe we don’t collect enough for this patient. So counseling them appropriately, and I call this the GVHD of gene therapy, because it’s the uncertain, it is the unknown part of how long it will take. We know, we have learned and shared data, so age is a good prognostic. If you are younger than 18, usually one or two cycles is enough, but older than that, they can really have challenges in that. Within this phase also, it’s so important to optimize mobilization. So currently in sickle cell, plerixafor has been the agent that we use. But there is exciting data that was shared from the kingdom of Saudi Arabia, where they have done GCSF plus plerixafor. I do want to provide word of caution. This really needs to be careful because GCSF is associated with mortality and morbidity, so it has to be done carefully and in a very well-established setting. But we shared our data with using a newer agent called motixafortide in 15 patients, and this is exciting because it is similar to plerixafor but seems to be more potent and more data to come because we provide that about collection we need to see how this will perform during infusion.

The third phase which is the chemotherapy we shared our real world data from using busulfan and how from once-a-day dosing to Q6 to decrease the risk of veno-occlusive disease, how to manage the neutropenia that it seems to be late, but it’s prolonged, but also exciting, there is newer gene therapy, like the one that used base editing, as in the study with BEAM, that shortened the duration of neutropenia significantly. So it’s more exciting and I want people to look forward to the future. 

And finally, it was about the fertility and some of the long-term data. It is so important to be able to gather information about the long-term data for this patient, not only from a pain crisis, but how’s their end organ function? Lung, kidney, liver. So we establish in collaboration with many other centers, the region consortium where we are collecting information from our patient that can help us guide for the future. If a patient has vasculopathy, pulmonary hypertension, how do they do? So that’s really exciting time now. And I hope we see more centers collaborating with us in this consortium.

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