Preliminary data suggest UCART19 is safe, effective

Thirteen patients had prior allogeneic stem cell transplants.

Nine patients had a bone marrow tumor burden of more than 25% blasts prior to lymphodepletion.

As of the cutoff date of October 23, all patients had been treated with UCART19.

Four of the pediatric patients are still on the trial. Two are in remission, one has relapsed, and one is refractory.

Eight adult patients are still on trial. Three are in remission, three are relapsed, and two are refractory.

Safety

“UCART19 appears to show an acceptable safety profile based on the adverse events reported so far,” Dr. Benjamin said.

Nineteen patients experienced cytokine release syndrome (CRS), primarily grades 1 and 2. Eight patients had grade 1 and 2 neurotoxicity events, and two patients had grade 1 acute skin GVHD.

“In keeping with what is seen in some of the autologous CAR T-cell trials,” Dr. Benjamin explained, “prolonged cytopenias were seen, which we defined in these studies as grade 4 neutropenia or thrombocytopenia occurring at 42 days post-UCART infusion.”

Six of 21 patients developed prolonged cytopenia.

There was also an increased incidence of viral infections occurring in eight patients, including cytomegalovirus, adenovirus, BK virus, and metapneumovirus.

“Most of these infections, however, were manageable,” Dr. Benjamin said.

Two patients developed neutropenic sepsis, one grade 5, which was one of the treatment-related deaths in the CALM trial.

No treatment-related deaths occurred in the PALL study, but there were two in the CALM study—one from pulmonary hemorrhage and the other from neutropenic sepsis and grade 4 CRS.

Twelve patients are still alive, five of whom are in CR.

Efficacy

Of the patients who received FCA lymphodepletion, 82% (14/17) achieved CR/CR with incomplete hematologic recovery (CRi), and 71% (10/14) achieved MRD negativity.

An additional patient gained MRD-negative status after the second dose of UCART19.

Of the 14 patients who achieved a CR/CRi, 78% (n=11) went on to receive an allogeneic transplant.

In the entire pooled population, 67% (14/21) achieved CR/CRi.

Three patients received a second UCART19 dose, and five patients remain in CR/CRi.

UCART19 expansion

UCART19 expansion, as measured by quantitative polymerase chain reaction in PALL and flow-based methods in CALM, occurred primarily in the first 28 days in the FCA-treated population.

Investigators observed expansion in 15 of 17 patients treated with FCA. None of the patients who received FC alone (n=4) had expansion detectable in blood or bone marrow, Dr. Benjamin noted.

“The response we’ve seen in the study so far,” Dr. Benjamin clarified, “is linked to the expansion observed within the first 28-day period.”

UCART cells persisted in three patients beyond day 42. In one patient, they persisted up to day 120.

“Of interest is the T-cell recovery seen in the study,” Dr. Benjamin elaborated. “We only have data from the adult study here—14 patients. And you’ll see that, in the FCA-treated arm (n=11), you have a deeper and more sustained lymphodepletion compared to the FC-treated patients (n=3). And this may play a role in the subsequent UCART19 expansion and disease response.”

Re-dosing

Of the three patients who were re-dosed, two achieved MRD negativity.

One patient achieved MRD-negative status at day 28 but relapsed and received a second infusion 3 months after the first dose. The second expansion was not as deep as the first, but the patient nevertheless achieved MRD negativity after the second dose.

The second patient received FC lymphodepletion and was refractory at day 28.

“The second time around, he received FCA, had a slightly better expansion, and achieved molecular remission,” Dr. Benjamin said.