Blood test may predict response to CAR T-cell therapy in relapsed multiple myeloma
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A simple blood test that measures lymphocyte count may accurately predict response to chimeric antigen receptor T-cell therapy among patients with relapsed multiple myeloma, according to study results.
Nearly all patients with multiple myeloma eventually relapse. CAR T-cell therapy that targets B-cell maturation antigen (BCMA) — a protein expressed at high levels on the surface of multiple myeloma cells — is one potential treatment option for patients whose disease progressed on other therapies.
Mark Bustoros, MD, assistant professor of medicine at Weill Cornell Medicine, and colleagues analyzed data from 156 patients with relapsed multiple myeloma who received anti-BCMA CAR T-cell therapy at one of three centers between 2017 and 2013.
Investigators obtained absolute lymphocyte count (ALC) 5 days prior to CAR-T infusion and for the first 15 days of BCMA CAR-T.
Results showed patients with higher ALC at day 15 achieved significantly better response to CAR-T than those with lower counts.
For example, patients with maximum ALC higher than 1 x 103/L exhibited more than a fivefold improvement in PFS compared with those who had maximum ALC below that threshold (median, 33.1 months vs. 6 months). Patients who had maximum ALC of 0.5 x 103/L or lower achieved significantly shorter PFS than those with higher maximum ALC (HR = 3.4; 95% CI, 2-5.8).
“This could be important to clinical practice because it could help guide physicians in making treatment decisions for these patients,” Bustoros told Healio. “This information helps physicians determine which patients are more likely not to respond or to relapse sooner.”
Healio spoke with Bustoros about the findings and how they may help guide patient selection for CAR T-cell therapy.
Healio: Why did you conduct this study?
Bustoros: CAR T-cell therapy has been revolutionary for multiple myeloma and other B-cell malignancies and blood cancers. However, not all patients respond well to CAR-T. It’s also an expensive therapy. We wanted to understand whether there are biomarkers that could guide physicians as to which patients would respond well and who would not, or who might be most likely to relapse after CAR-T.
Healio: How did you conduct this study?
Bustoros: We started with a cohort of patients with relapsed or refractory myeloma who underwent BCMA CAR-T. The analysis included patients treated with ciltacabtagene autoleucel (Carvykti; Janssen, Legend Biotech) or idecabtagene vicleucel (Abecma, Bristol Myers Squibb).
Healio: What did you find?
Bustoros: ALC is predictive of deeper response. Patients with higher ALCMAX — the highest value for any patient in the first 15 days after infusion — tended to have deeper response. Then we assessed a more important question: How does this affect PFS? We found a strong signal that patients who had higher ALCMAX tended to have longer PFS.
This was reassuring, but we wanted to be sure our observation was strong and could be generalized. In collaboration with another academic center, the signals or observations we found in our initial cohorts were replicated and even amplified when we had a larger number of cases.
We tried to account for confounders like patient age, number of prior lines of therapy, high-risk cytogenetics and other high-risk characteristics. We did this to be sure that ALC would still be an independent prognostic factor for disease progression and relapse after CAR-T. After accounting for these confounders, we still found that ALC as a continuous variable but also that the cutoff we established was associated with better PFS and depth of response.
Healio: How might this finding help guide treatment decision-making in multiple myeloma or patient selection for CAR-T?
Bustoros: We now know that patients who have very low ALC counts in the first 15 days after infusion are likely to progress faster. Then we can prepare or try to look for other therapies for when the patient does eventually relapse. Those who relapse after CAR-T will not have a lot of other options. If we know from this biomarker that these patients won’t respond as well, we can plan our next strategy for their treatment.
Healio: What are your next steps in research?
Bustoros: We want understand the factors that contribute to low ALC count vs. higher ALC counts. We’re digging deeper into the biology itself, collecting patient samples and doing more sophisticated analysis to understand the factors that contribute to this phenomenon. We found a clinical correlation, but we want to understand the biological differences and how we can use those to make an even earlier determination about whether the collection of the patient’s T cells and the subsequent treatment would be successful.
Reference:
For more information:
Mark Bustoros, MD, can be reached at mab4033@med.cornell.edu.
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