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CD49d-Positivity Is the Strongest Flow Cytometry–Based Predictor of Overall Survival in CLL

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Key Points

  • CD49d-positive patients had significantly poorer overall survival and treatment-free survival.
  • CD49d status was the sole flow cytometry–based marker that was an independent predictor of overall survival.

In a study reported in the Journal of Clinical Oncology, Bulian et al found that CD49d-positive chronic lymphocytic leukemia (CLL) patients have significantly poorer overall survival and treatment-free survival and that CD49d status is the strongest flow cytometry–based predictor of overall survival in CLL.

Study Details

The study was a worldwide multicenter analysis using data on 2,972 cases of CLL from published and unpublished series to evaluate the impact of CD49d as a predictor of overall survival and treatment-free survival. In training and validation sets, the optimal cutoff for CD49d-positivity was found to be ≥ 30% of neoplastic cells expressing CD49d. In total, 37% of patients were CD49d-positive.

Poorer Overall Survival and Treatment-Free Survival

In a pooled analysis of training and validation sets, CD49d-positive patients had a significantly increased risk of death (hazard ratio [HR] = 2.5, 95% confidence interval [CI] = 2.1–3.0), with significantly lower 5-year (87% vs 94%) and 10-year overall survival (62% vs 84%) compared with CD49d-negative patients (P < .001). CD49d-positive patients had significantly increased risk of receiving treatment (HR = 2.3, 95% CI = 2.0–2.6), with significantly lower 5-year (42% vs 68%) and 10-year treatment-free survival (24% vs 50%) compared with CD49d-negative patients (P < .001).

Independent Predictor

In a multivariate model including 1,117 cases with all prognostic information available and adjusting for disease stage, sex, age, and other clinical and biologic prognostic factors, including absolute lymphocyte count, β2-microglobulin, del11q and del17p, IGHV mutation status, and expression of the flow cytometry–based indicators CD38 and ZAP-70, CD49d-positive patients had a twofold increased risk of death (HR = 2.0, 95% CI =1.4–3.0) and CD49d-positivity was the only flow cytometry based–marker that independently predicted overall survival.

Other independent predictors of overall survival were age, sex, IGHV mutation status, del17p, and absolute lymphocyte count. In a model excluding CD49d, both ZAP-70 (HR = 1.60, 95% CI = 1.06–2.41) and CD38 (HR = 1.56, 95% CI = 1.08–2.26) regained independent prognostic value.

Hierarchic tree models including all patients, only those with early-stage disease, or only those aged ≤ 65 years always selected CD49d as the most important flow cytometry–based biomarker, with CD38 and ZAP-70 providing negligible additional prognostic information. Consistent with the hierarchic tree models, bivariate analysis showed that CD49d reliably identified patient subgroups with poorer overall survival and treatment-free survival independent of CD38 and ZAP-70 status.

As stated by the investigators, “Overall, these data show that among CLL phenotypic markers, CD49d has a greater prognostic importance than CD38 or ZAP-70 and demonstrate the additional value of CD49d testing when CD38 and ZAP-70 information is available.”

They concluded, “In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry–based predictor of [overall survival and treatment-free survival] in CLL.”

Pietro Bulian, MD, of the Istituti di Ricovero e Cura a Carattere Scientifico, Centro di Riferimento Oncologico, Aviano, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by the Ministero Della Salute, Fondazione Internazionale di Ricerca in Medicina Sperimentale, Associazione Italiana Contro le Leucemie, Linfomi e Mielomi, and others. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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