Therapeutic CAR T cells administered to leukemia patients in a clinical trial offer long remissions associated with T cells that persist out to at least 4 years
In the adult population, chronic lymphocytic leukemia (CLL) is the most common type of leukemia. Although numerous effective treatment options are available, CLL remains incurable in the general population using conventional therapies. Disease progression is inevitable, and overall survival can range from 2 to 20 years.
Patients with refractory CLL (not responsive to therapy) have an especially poor prognosis. Whereas some patients can be cured with allogeneic stem cell transplantation, the procedure is associated with extensive morbidity and mortality (discussed here). Furthermore, not all patients meet the criteria for the procedure and are therefore not eligible for transplant therapies.
We previously discussed early results from a clinical trial utilizing therapeutic “CTL019” CAR T cells in acute lymphoblastic leukemia patients (discussed here). Now, a research team evaluated CTL019 CAR T cells for therapeutic intervention in CLL patients who had relapsed or were refractory. The overall response rate was 57% (8 out of 14 patients), with 4 complete responses and 4 partial responses.
This team demonstrated that the expansion of CAR T cells in the patients correlated with clinical response. Moreover, CAR T cells persisted and remained functional beyond 4 years in 2 patients who achieved complete response.
We have previously discussed minimal residual disease (discussed here), whereby cancer stem cells are left behind following therapy. These remaining cancer stem cells can give rise to the disease years later. However, the CLL patients who achieved complete response following treatment with CTL019 CAR T cells had no detectable minimal residual disease, even out to 4 years.
Could there finally be a safe alternative to stem cell transplantation for CLL patients who have no other recourse? One has to admit, there is potential. The next step will be to define the criteria for the patient population who will respond to CTL019 CAR T cells. This approach will eliminate an involved therapeutic intervention in patients who may not benefit.
1. Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015 Sep 2;7(303):303ra139