Nonviral gene transfer of CARs tested in humans
The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.
Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).
All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.
Five patients received a CAR T-cell dose of 106, 6 patients received 107, 5 received 5x107, and 3 received 5x108 cells/m2 based on recipient body surface area.
Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.
Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.
“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.
And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.
Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.
Persistence of infused T cells
The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.
“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.
He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center. 
