Luca Bertamini, MD, hematologist at Erasmus University Medical Center in Rotterdam, Netherlands, sat down for an interview with _Pharmacy Times®_ to discuss new data from the PERSEUS trial he presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego. In the trial, Bertamini and his colleagues found that circulating tumor cells (CTC) could serve as a biomarker for poor outcomes in patients with newly diagnosed multiple myeloma (MM) who are transplant eligible. Furthermore, in these patients, treatment with daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd) led to sustained and durable survival and minimum residual disease (MRD-negativity after being deemed high-risk.
Bertamini highlights how pharmacists can use biomarkers such as these to better predict patient response to treatment and create more optimized treatment plans, tailored to their condition and disease status. Additionally, Bertamini discusses future steps in evaluating CTC and MRD, including better curation of treatment depending on patient resistant to therapy.
**_Pharmacy Times:_** Can you discuss the implications of the observed correlation between high circulating tumor cell levels and inferior PFS in the PERSEUS trial?
**1\. Circulating Tumor Cells (CTCs) as a Prognostic Biomarker:** The presence of CTCs in myeloma patients is strongly associated with inferior progression-free survival (PFS), independent of other risk factors. This simple biomarker could be a valuable tool for identifying high-risk patients who may benefit from more intensive treatment.
**2\. D-VRd Regimen Improves Outcomes:** The addition of daratumumab to the VRd regimen (bortezomib, lenalidomide, and dexamethasone) has shown improved PFS and deeper, more durable MRD negativity in myeloma patients. This is particularly beneficial for high-risk patients with elevated CTC levels.
**3\. Future Directions for CTC Research:** Ongoing research aims to further explore the role of CTCs as a prognostic factor in different patient settings, including transplant-ineligible patients and those receiving various treatment modalities. The goal is to integrate CTC testing into clinical practice and real-world settings to optimize patient care.
**Luca Bertamini:** One of the most important findings that we had when we investigated the prognostic impact of circulating tumor cells (CTC), which are myeloma cells that can be found in the blood of patients before receiving treatment in the context of the PERSEUS study, is that this biomarker, which is very simple to test in a clinical practice, is strongly associated with an inferior progression free survival (PFS), and this is also independent of other risk factors. This is really important, because when we want to implement a new biomarker for certified patients, the first thing we want to know is if this is going to add something on top of what we already know as an important risk factor. This is really a key, important finding that we found.
**_Pharmacy Times:_** How can pharmacists and health care providers utilize the knowledge of which patients are particularly high-risk of poor outcomes to optimize their care?
**Bertamini:** That's a really great question. At the moment, what we do for myeloma is we treat all patients with exactly the same treatment approaches, whether they are high risk or low risk. What is important is also knowing new treatment approaches, like the one that was tested in the PERSEUS study—daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd)**,** transplant, followed by daratumumab maintenance—also benefits this subset of patients. The important information here is that, even though patients with high levels of CTC perform worse, they still benefit from receiving this optimal therapy.
**_Pharmacy Times:_** Could you elaborate on how adding daratumumab to VRd led to better patient outcomes?
**Bertamini:** The addition of daratumumab to VRd, and also to our maintenance in this transparent-eligible setting, really improved PFS. But not only that, there's a very important end point which now we are very interested in, which is minimal residual disease (MRD) negativity. In this study, and also in this sub-study that we did looking at the impact of CTC, patients receiving the optimal treatment—D-VRd—achieved a deeper and more durable MRD negativity. This is really important for predicting which patients will have a longer PFS and better prognosis.
**_Pharmacy Times:_** How can the role of CTC as a prognostic factor for outcomes in myeloma be studied further in the future?
**Bertamini:** That's a great question. I'm really working on trying to bring this biomarker into the next step forward, into clinical trials and also in clinical practice. I think what is really important is achieving an agreement with other experts on how to implement this biomarker and it’s risk stratification, and also understand it's prognostic impact in other patient settings—patients that don't receive transplant, that are older, transplant ineligible, and that receive different type of therapies. And not only patients enrolled in trials, because in the end, what we want to really know is, what is the impact of a biomarker in the clinical practice and the real world? But we are doing this in a big collaboration in Europe, so I hope I can show you this data soon.
**_Pharmacy Times:_** How can pharmacists incorporate better monitoring and management of CTC into their treatment protocols and practices?
The **66th ASH Annual Meeting and Exposition** takes place from Saturday, December 7 to Tuesday, December 10 in San Diego, California. You can follow our [continuing coverage here](https://www.pharmacytimes.com/conference/ash).
**Bertamini:** At the moment, the evidence that we are bringing is testing CTC before treatment. It will be also interesting to see if we could monitor disease and response to therapy with just a blood sample instead of using what we now use, which is bone marrow spirit, and minimal residuals in the bone marrow. I think it's really important for future studies to really investigate methods that could look at the decreased levels and the residual CTC levels, that could also address which patients are resistant to therapy and which patients are really responding well.
**_Pharmacy Times:_** Is there anything else you would like to add?
**Bertamini:** I'm really happy to be here and present this data. I think this biomarker is really, really strong, as has been shown—that it's prognostic across different centers and in different type of treatment settings. I think it will be really important for us to have it tested in the future, in the practice, for our patients.