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T cells
Image from NIAID

LISBON—Preliminary data from a phase 1 trial suggest UCART19 can serve as a bridge to transplant in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).

This “universal,” donor-derived, chimeric antigen receptor (CAR) T-cell therapy produced complete responses (CRs) in 6 of 9 patients treated.

Five of the patients who were negative for minimal residual disease (MRD) proceeded to allogeneic hematopoietic stem cell transplant (allo-HSCT).

Two of the 5 patients were still alive and in MRD-negative remission at last follow-up, but 1 had relapsed and 2 died.

A total of 4 patients died in this trial—1 from a dose-limiting toxicity (DLT), 1 from progressive disease, 1 from infection, and 1 from pulmonary hemorrhage.

“These early results for UCART19 are very encouraging, both in terms of manageable safety and the impressive complete molecular remission rate in these hard-to-treat adult patients with R/R B-ALL,” said principal investigator Reuben Benjamin, MBBS, PhD, a consultant hematologist at King’s College London in the UK.

Dr Benjamin presented these results, from the CALM trial, at the 44th Annual Meeting of the EBMT (abstract OS10-4*).

The CALM trial is sponsored by Servier. In 2015, Servier acquired exclusive rights from Cellectis for UCART19, which is being co-developed by Servier and Pfizer.

Patients and treatment

Dr Benjamin presented results in 9 patients with R/R B-ALL who had a median age of 23 (range, 18-49).

All patients had morphological disease or an MRD level of at least 1 x 10-3 (via flow cytometry and/or qPCR) at baseline. The median disease burden was 8% (range, 0-95).

Four patients had received 1 to 3 prior therapies, and 5 had received 4 or more prior treatments. Six patients had prior inotuzumab ozogamicin, 2 had prior blinatumomab, and 7 had prior allo-HSCT. The median time to relapse after allo-HSCT was 5.9 months (range, 4.1-11).

Patients underwent lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab (n=8) or fludarabine and cyclophosphamide (n=1).

They received UCART19 at 2 dose levels—6 x 106 total cells (n=6) or 6 to 8 x 107 total cells (n=3).

Toxicity

There were 2 DLTs, 1 at each dose level. At the lower dose, the DLT was grade 4 cytokine release syndrome (CRS) associated with grade 5 neutropenic sepsis. The patient with this DLT died at day 15 post-infusion.

At the higher dose level, the DLT was grade 4 prolonged cytopenia associated with infection and pulmonary hemorrhage. This patient died at day 82 post-infusion, 19 days after undergoing allo-HSCT.

In all, 8 patients had CRS. One patient had grade 1, 6 had grade 2, and 1 had grade 4 CRS. Seven patients had complete resolution of CRS.

Two patients had neurotoxic events, both grade 1.

Three patients had prolonged cytopenia, all grade 4. This was defined as persistent neutropenia and/or thrombocytopenia beyond day 42 after UCART19 infusion, except if the patient had >5% bone marrow blasts.

Two patients had neutropenic sepsis, grade 4 and grade 5.

Three patients had cytomegalovirus infection, all grade 2. Two patients had adenovirus infection, grade 1 and grade 3.

One patient had grade 1 acute cutaneous graft-versus-host disease.

Efficacy

Six of 9 patients achieved a CR, and 5 were MRD-negative by flow cytometry or qPCR. All 5 patients proceeded to allo-HSCT.

After transplant, 2 patients were still MRD-negative at 8 months, 1 patient relapsed after 6 months, and 2 patients died while MRD-negative. The deaths were due to infection and pulmonary hemorrhage.

Two other deaths were due to a DLT (neutropenic sepsis associated with CRS) and progressive disease.

Of the 5 patients who are alive, 2 are still MRD-negative after allo-HSCT. One of these patients relapsed after the first UCART19 infusion, received a second infusion, and achieved an MRD-negative CR that enabled transplant.

The remaining 3 patients who are still alive did not undergo transplant. One of these patients relapsed after achieving MRD-positive remission, and 1 relapsed after MRD-negative remission. The third patient relapsed and received a second UCART19 infusion. This patient has yet to respond to the second infusion but has minimal follow-up.

Recruitment in this study is ongoing at the higher dose level—6 to 8 x 107 total cells.

*Data in the abstract were updated in the presentation.


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