A patient-reported questionnaire may eliminate the need for an ophthalmic exam before belantamab mafodotin dosing in TI NDMM
Prof Evangelos Terpos - University of Athens, School of Medicine, Athens, Greece
This is a very interesting study also. For example, two years now we are investigating the role of belantamab mafodotin at the first line in patients who are transplant ineligible, especially those who are intermediate fit and frail and who have a phase I/II study with a combination with belantamab, lenalidomide and dexamethasone. We have now three different doses of belantamab: 1.4mg/kg, 1.9mg/kg and 2.5mg/kg given every 8 weeks, which is a totally different schedule compared to the relapsed/refractory setting in the DREAMM-7 and in the DREAMM-8. Belantamab is given at the dose of 2.5mg/kg every 3 weeks in the DREAMM-7 and in the DREAMM-8 it is every 4 weeks but 2.5mg/kg for the first cycle and then it goes to 1.9mg/kg every 4 weeks.
So we go out of this schedule, a maximum monthly schedule, and we go to once every 2 months and if we have any ocular problem then we may go to up to 12 months. So we give belantamab mafodotin once in 2-3 months in the majority of the patients in combination with the standard doses of lenalidomide and dexamethasone.
The study had two important questions to answer. The first is what is the best dose of belantamab in order to remain the efficacy and having low ocular toxicity. From the first part of the study we found that the dose of 1.9mg/kg given every 8 weeks had a very good response rate of almost 100% and the ocular toxicity is very low. Grade 3 or more keratopathy, for example, was only less than 5% of the patients.
So at the second part of the study we wanted also to see if we can avoid the ophthalmology. So what we did, we randomised the other 30 patients to two groups. First of all both groups had an ophthalmology examination before each dose of belantamab mafodotin but also they had a questionnaire that we have the OSDI, as we call it, questionnaire that includes symptoms from the eyes and also if the symptoms can affect the daily living. For example, there were questions like how painful or gritty or sore are your eyes or do you have any blurred vision? This is the symptom part of the question and you have the second part which is how the symptoms can affect your quality of life. There are questions, for example, if you can read, if you can go to work, if you can read your smartphone or your laptop or your computer, if you can watch television. So these are very important.
According to that, we had two schedules. In the first group the reductions either in the dose, which was to give 1.9mg/kg every 3 months, or every 12 weeks, is driven by the ophthalmology examination. In the second group where we had the ophthalmology examination it was driven by the effects of the symptoms in the everyday living activities. So in order to know if these can go together or if we have definitely to have the ophthalmology examination in order to drive us to reduce the dose of belantamab or to increase the length of the administration.
What was the important thing is that the two groups had similar findings. The ophthalmology examination and the questionnaire had similar results. There was discordance only in one patient. So this means that possibly if we are having this tool, this anamnestic tool, as we call it, in a bigger study, a phase III study for example, then we may be able to reduce dramatically the ophthalmology examination, to have it only in the first two or three cycles of treatment and then the doctors, based on this questionnaire, would be able to see how often we will give the belantamab mafodotin and at what dose.
This is extremely important because we know that the burden of the ophthalmology examination in each cycle of belantamab mafodotin administration is very heavy for several centres. We are very near to finding how to give belantamab mafodotin in our patients in the absence of an ophthalmologist, at least after the first two or three cycles
