OPTIMISMM Trial for Myeloma | Meral Beksac, MD | IMS 2023

Hi, my name is Meray Beksac. I'm a professor of hematology in Ankara University, Turkey. Here I am at the International Lylo-Mal Society meeting 2023, and I will be presenting an abstract on the value of adding polendomide to the backbone of portisome and dexamethasone. This study named Optimism was published a couple of years ago, and the results were focusing on the level of the efficacy, which means the effects and the productivity and the response rates achieved with this triple combination, the combination of three drugs, polendomide, portisome and dexamethasone, comparing to a doublet, a two-drug regimen, which is portisome and dexamethasone. In that earlier report, it was possible to say that using three drugs is better than two drugs. The study population consisted of patients who are diagnosed with myeloma, but who have received earlier multiple treatments up to three lines of therapy. These patients are such that they all had a history of using polendomide, and more than 70% of patients were already refractory to polendomide. So this is a patient profile who is still sensitive to portisome, but have become refractory, who are not anymore responding to polendomide. The same class of agent with polendomide. Polendomide is a more effective drug that can be used in this combination, and we today very well know that using more drugs is most of the time more efficient. And this triple drug combination of polendomide, portisome and dexamethasone, was shown earlier to be more efficient. And today we are proving for the first time the impact of efficiency not only on the depth of response, but also on the survival advantage. When authorities are giving approval, they prefer to have a survival advantage. And for the patients, the depth of response is of importance. They want to see the bigger, the deeper the response, it is better. This is very well recognized by the community, by patients, by physicians, by reimbursement authorities, but moreover, having a survival advantage is something which comes later. So the importance of this study is that we are able to show the overall survival advantage here, and we are showing that the patients who were not able to get polendomide at the first randomization because of the treatments were chosen three-drug versus two-drug, and the patients who were in the two-drug arm, after a while, when they progressed, they had to get a subsequent therapy. And like 58% of those patients in the control arm eventually received polendomide. So this is kind of a study where you receive polendomide early on or later, and in the end it shows that having a drug such as polendomide will have an impact on your overall survival. And it is true that the ratio of treatment with a three-drug regimen is double the duration that you can achieve with a two-drug regimen. So for patients who are in the relapse situation, it's better to have more drugs, and in that case, the question arises where if this kind of approach is tolerable, are the toxicity is also increasing, and here we are providing answers that it is tolerable and the toxicity is related to the decrease in the counts of platelets is comparable in the three versus two-drug regimen. We see more neutropenia, which means the white cell counts are lower with the three-drug regimen. This can be manipulated easier by the physicians, either reducing the dose or trying to add growth factors. And the other side effects such as the impairment on the neurological functions, the neuropathy, which is an important issue for patients who are on long-term bortism, it was not of high frequency, only four versus eight percent in the two arms. But this was the number one leading cause of discontinuation of therapy. So for future, there is a space to improve the bortism abuse because when the trial was designed, the drug was given intravenously and then it was converted to subcutaneous. Today, if we use this triple combination, the toxicity we expect will be less.