Factors Impacting DFS in B-Cell Malignancy After CAR-T Administration

05/18/18

A recent study sought to determine the factors associated with durable remission after a complete response to CD19-targeting chimeric antigen receptor T-cell (CAR-T) therapy in adult patients with B-cell acute lymphoblastic leukemia (B-ALL).

The study will be presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting (June 1-5, 2018; Chicago, IL).

CD19-targeting CAR-T therapy has shown the ability to produce high complete remission rates in adult patients with B-ALL. However, factors associated with durable remission are not fully understood.

Kevin Anthony Hay, MD, MSc, Fred Hutchinson Cancer Research Center (Seattle, WA), and colleagues conducted a study to help better understand the factors associated with durable remission in this setting. A total of 56 patients who received CD19-targeting CAR-T therapy at or below the maximum tolerated dose with at least 6 months of follow-up data were included.

Researchers assessed for factors impacting disease-free survival (DFS) and overall survival (OS).

After a median follow-up of 27.4 months, researchers reported that 89% (n = 50) of patients achieved morphologic complete remission and 80% (n = 45) achieved complete remission without minimal residual disease by flow cytometry.

Patients who achieved complete remission without minimal residual disease demonstrated better median OS compared with those with morphologic disease (16.8 vs 2.7 months, respectively; P = .03). Univariate analyses also showed longer DFS with lower LDH (P = .0007), no extramedullary disease (P = .005), lower marrow blasts (P = .013), cyclophosphamide/fludarabine lymphodepletion (P = .004), and higher CAR-T dosage (P = .033).

A stepwise multivariable model confirmed the associations between cyclophosphamide/fludarabine lymphodepletion, low LDH, and absence of extramedullary disease before CAR-T infusion with more durable DFS.

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Dr Hay and colleagues noted that 18 of the patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) after achieving complete remission without minimal residual disease. Results showed that those with morphologic disease before CAR-T infusion may benefit from allogeneic HSCT.

“More durable DFS after achieving complete remission without minimal residual disease was found in patients with low DFS, no extramedullary disease, and cyclophosphamide/fludarabine lymphodepletion before CAR-T cells,” authors of the study concluded.—Zachary Bessette