General Updates | Safety considerations and clinical factors to assess when initiating thalidomide for thalassemia

So when, you know, when we started using thalidomide, it was a part of a clinical trial, right? So that’s how there was a kind of a protocol inbuilt in which in a proper way, how are we supposed to monitor the patients while they are on thalidomide. So every time a child was or a patient was started on thalidomide, we were supposed to monitor clinical parameters and the lab parameters. 

The clinical parameters included all kinds of adverse effects like somnolence, constipation. We would ask them about any new onset tremors, any, you know, any neurological problems, like any tingling of hands and feet, any difficulty in, you know, wearing slippers or combing your hair,any subtle thing, edema, ask for peripheral edema. So there’s a whole set of, you know, history questions that we included in our trial visit that had to be asked about. I think the most important part was to stress to ask for and look for early features of peripheral neuropathy because that was a concern and as patients started taking thalidomide, how it was affecting their quality of life, right? Some of our patients did complain of difficulty in sticking to their school activities or to their job, getting up early in the morning, having difficulties in getting up early in the morning to go to go to their school or job, whatever, right? So these were certain things which were there in the history part of it. Menstrual irregularities in women, because that, especially those who are sexually active, then that creates a lot of confusion. We ended up doing a urinary pregnancy test every now and then because thalidomide caused menstrual irregularities, and then every time a period was delayed, we had to get a urine pregnancy test, right? So this was the history part of it. 

Lab examination-wise, a complete CBC with a peripheral blood film done at every visit to look for neutropenia and thrombocytopenia, which was discovered in about 10 to 15 percent of patients. Nothing, I mean, none of our patients required any transfusion, but we had to stop the drug in a few patients because of severe neutropenia, which could have predisposed them to, you know, different febrile neutropenic episodes or sepsis, so that is something that we need to be careful about. And also the patients and parents have to be informed that, you know, in case the child develops fever, then it’s important to get a CBC done immediately and get in touch with the treating team because you never know whether that episode is a simple fever or is it a febrile neutropenia. Apart from that, we looked at liver and renal function tests. Something that we noticed was, because, you know, the transfusion requirement was going down, most patients developed a slight unconjugated hyperbilirubinemia while they were on thalidomide, but that was not concerning as such. And transaminitis was not a major issue. Out of about 180 patients, we stopped the drug because of transaminitis in just one patient. And it didn’t really affect administration of chelators as well, because most of our chelators can also cause transaminitis. So that was not really an issue. Then creatinine, as one patient during the trial, we had to stop the drug because of an AKI, which developed in association with a dengue fever. So these are certain things that we would do. And if we had any clinical evidence or history evidence of peripheral neuropathy, then we went ahead and did a NCV, a nerve conduction study, to confirm whether there is any evidence of peripheral neuropathy or not. 

Something very interesting that came up during discussion about luspatercept actually, we had a meeting recently where we discussed about doing your MRI spines before starting luspatercept and, you know, following it up, whether it leads to any increased extramedullary hematopoiesis. However, we’ve not done that with thalidomide, but that’s an interesting concept that probably if somebody is working on a trial to work on thalidomide, probably that can be done in future. 

And of course, I think I missed on the liver and spleen size when I said clinical examination that needs to be, because if you have, if a patient is on thalidomide and spleen is increasing, then you may want to go back to transfusions rather than putting the patient only on thalidomide and, you know, dealing with problems later on with extramedullary hematopoiesis, hypersplenism, and stuff. 

One major, you know, adverse effect that has been stated with thalidomide is a hypercoagulable state and hyperthromboembolic phenomena. Thankfully, in our cohort of about 180 patients who were followed up for almost one and a half to two years, there was no episode of thromboembolism, but we need to screen the patients, you know, if you feel your patient has a thromboembolism risk or has undergone splenectomy has a high platelet count, then it is worth considering adding aspirin to the therapy along with thalidomide, and a lot of studies that we mentioned earlier have actually put aspirin prophylaxis in place whenever patients were started on thalidomide, so depending on your patient’s profile and risk of thromboembolism, that’s something to be looked into.

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