SCOPE Score Validated as Predictive Tool for Outcomes With BCMA CAR T-Cell Therapy in R/R Multiple Myeloma

The development and validation of the Stratification of CAR-T Outcomes at Pre-Apheresis Evaluation (SCOPE) score introduces a clinically meaningful tool to predict response and toxicity outcomes in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR T-cell therapy, according to Yi Lin, MD, PhD.

Patients with a low-risk score (0 points) achieved superior outcomes compared with intermediate-risk (1–2 points) and high-risk (3–7 points) groups, including higher complete response or stringent complete response rates (58% vs 48% vs 35%; P < .001), improved 1-year progression-free survival (71% vs 52% vs 27%; P < .001), and longer 1-year overall survival (93% vs 80% vs 58%; P < .001).1 Toxicity risk was also strongly associated with higher SCOPE scores.

The prognostic capacity of the SCOPE model was externally validated in two independent cohorts, including a real-world dataset (n = 135; progression-free survival, P < .001) and the idecabtagene vicleucel arm of the phase 3 KarMMa-3 trial (NCT03651128; n = 212; progression-free survival, P < .001).

In an interview with OncLiv on-site at the 22nd Annual International Myeloma Society (IMS) Meeting and Exposition Lin shared that, “It's been a great collaboration with the many centers we work with, including pharmaceutical partners. I think this is a great example of how we can all work together more globally, especially in the context of the IMWG Immunotherapy Working Committee, to really ask time-sensitive and relevant questions for the practical applications of these therapies.”

Lin is a professor of medicine in the Divisions of Hematology and Experimental Pathology and Laboratory Medicine at Mayo Clinic in Rochester, Minnesota.

OncLive: What was the rationale and primary objective of this study?

Lin: At IMS 2025, David Cordas dos Santos, MD, of [Dana-Farber Cancer Institute] presented on the SCOPE Myeloma study. That's a project that he and I worked on, along with Kai Rejeski, MD, of [Memorial Sloan Kettering Cancer Center] and Doris Hansen, MD, [of Moffitt Cancer Center].

[This represents] the largest dataset to date of [close to] 1200 patients with multiple myeloma who were treated with CAR T-cell therapy, either idecabtagene vicleucel (ide-cel; Abecma) or ciltacabtagene autoleucel (cilta-cel; Carvykti). It includes [real-world patients] from many sites in the US and Germany, along with the registration trial data from [the phase ½ CARTITUDE-1 (NCT03548207) and phase 2 KarMMa-3 (NCT0365112) trials].

With this very large dataset, we're able to do both [internal and external] validation to ensure the relevance of this model. The biggest concept shift [with this study] is that we have prognostic models right now, predictive tools for nonrealapsed mortality, cytopenia, infections, survival. However, these are all scores using clinical information at the time of [lymphodepleting] chemotherapy, so at the time that you're ready to start CAR T-cell therapy treatment.

By that time, the CAR T cells [have] already [been manufactured]. A big part of that decision [has] already [been] made, right? We [have] committed the patient to collect the cells to make this very expensive CAR T-cell therapy.

We've already tried to manage patients’ active myeloma during the CAR T-cell therapy manufacturing time, and that may be in the context of choosing not to give them a different therapy with the intent of controlling the disease [using CAR T-cell therapy]. The most relevant decision point is really before leukapheresis, at the time that we're evaluating patients for CAR T-cell therapy eligibility. That is the time where we're talking about the relevance of CAR T therapy compared to other therapy options, and the time when you could potentially modulate some of the risk factors even during CAR T-cell therapy manufacturing.

That's the concept for SCOPE Myeloma; [we were] looking at what clinical information at the time of CAR T-cell evaluation before the cells are collected for manufacturing—can predict for [progression-free survival, overall survival, non-relapse mortality, cytokine release syndrome, infections, and other outcomes].

What clinical factors were identified as most predictive of response or early relapse risk in patients being evaluated for CAR T-cell therapy?

What we found is that we can identify some readily available clinical information, such as the HEMATOTOX score, but taken at [the pre-apheresis timepoint], and other myeloma risk features like plasma cell burden, LDH, and prior BCMA exposure. When combined, this information can already give us a good idea if this patient could be an excellent responder, or potentially at very high risk of relapsing early, and everywhere in between.

How might these findings influence future clinical practice?

Because this large dataset is already validated, the International Myeloma Working Group Immunotherapy Committee is formally recommending the use of the score prospectively for patients receiving CAR T-cell therapy, whether on clinical trial or in real-world practice, so that we can uniformly describe this risk feature for patients going into their treatment.

What we're hoping to see, of course, is that by using something like SCOPE Myeloma more consistently, we will understand the risk features of patients in the real world who are getting treatment, or of patients in clinical trials with next-generation CAR T-cell therapy moves into earlier lines of therapy.

What's most interesting as the next step is really to look at whether risk stratification at that time point can be used in targeted, prospective interventional studies. For example, if [we have a patient who is] higher risk, is that a modifiable risk where we can improve the outcome of CAR T-cell therapy, or is it such a high risk that we should be studying whether there are better ways to intervene beyond current CAR T-cell therapeutic modalities?

References

1. Dos Santos D, Rejeski K, Lin Y, Development and Validation of the SCOPE-MM Score: A Pre-Apheresis Risk Model Predicting Response and Toxicity in RRMM Patients Receiving BCMA-Directed CAR-T Therapy. Presented at the 22nd International Myeloma Society Annual Meeting; Toronto, Canada; September 17-20, 2025. Abstract OA-03.
2. Rejeski K, Hansen DK, Cordas Dos Santos DM, et al. Pre-Apheresis Prediction of Toxicity and Response in Patients Receiving BCMA-Directed CAR-T for Relapsed/Refractory Multiple Myeloma. Blood. 2024;144(Supplement 1):895-895. doi: doi.org/10.1182/blood-2024-208376