CD5 CAR-T Cells Induce Responses in Relapsed/Refractory T-Cell Lymphomas

CD5-directed chimeric antigen receptor (CAR) T cells can produce responses in patients with relapsed or refractory T-cell lymphoma, according to research published in Blood.

Researchers tested CD5-directed CAR T-cell therapy in patients with relapsed or refractory T-cell lymphoma in a phase 1 trial (ClinicalTrials.gov identifier: NCT03081910).

The trial enrolled 17 patients who had more than 50% CD5 tumor expression, and 13 patients had CAR-T cells manufactured.  

Ultimately, 9 patients received CD5 CAR-T cells. Their median age was 63 (range, 29-71) years. The patients had peripheral T-cell lymphoma (n=4), cutaneous T-cell lymphoma (n=2), angioimmunoblastic T-cell lymphoma (n=2), and adult T-cell leukemia/lymphoma (n=1).

The patients had previously received a median of 5 prior lines of therapy (range, 2-18). Three patients had received an autologous hematopoietic stem cell transplant (HSCT), and 2 had received an allogeneic HSCT.

On study, patients received CAR-T cells after lymphodepleting chemotherapy (fludarabine and cyclophosphamide). Patients received 1 dose of CAR-T cells (n=7) or 2 doses (n=2) at 1 of 3 dose levels: 1 x 10⁷, 5 x 10⁷, or 1 x 10⁸ CAR+ cells/m².

Four patients (44%) achieved a response to this therapy, 4 patients had progressive disease, and 1 patient had stable disease.

Two patients — 1 with AITL and 1 with PTCL — achieved a complete response (CR) after a single CAR T-cell infusion. Both patients declined consolidative HSCT. The AITL patient had a recurrence, received salvage therapy, and was still alive at last follow-up. The PTCL patient had a relapse and went on to receive radiation and HSCT but ultimately died from transplant-related complications.

One patient with ATLL had a partial response after the first CAR T-cell infusion but had progressive disease after a second infusion and went on to receive salvage therapy.

One patient with AITL had a mixed radiographic response after the first CAR T-cell infusion, received a second infusion, went on to HSCT, and remains in CR at 41 months after transplant.

Four patients — 2 with CTCL and 2 with PTCL — had progressive disease after the first CAR T-cell infusion and ultimately died. One patient with PTCL had stable disease after CAR T-cell infusion but later died in CR after receiving salvage therapy.

Four patients had cytokine release syndrome (CRS), and 5 had a neurologic event (headache [n=3], confusion, and delirium). All of these events were grade 1-2 in nature.

Other common adverse events of any grade were decreased platelet count (n=4), febrile neutropenia (n=4), and AST increase (n=4).

“These results demonstrate that CD5.CAR-T cells are safe and can induce clinical responses in patients with r/r [relapsed/refractory] CD5-expressing TCLs [T-cell lymphomas] without eliminating endogenous T cells or increasing infectious complications,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor