CD19-targeted CAR T-cell treatment for CNS and other extramedullary disease

Active CNS disease at relapse and/or infusion.

Active CNS disease at relapse and/or infusion.

A single-center report analyzed 195 sequential patients treated with 4-1BB CD19-targeted CAR T cells, 66 of whom had CNS disease (43 with isolated CNS disease, 23 with combined bone marrow/CNS disease).[186]

Active CNS disease at relapse and/or infusion. › A single-center report analyzed 195 sequential patients treated with 4-1BB CD19-targeted CAR T cells, 66 of whom had CNS disease (43 with isolated CNS disease, 23 with combined bone marrow/CNS disease).[186]

Overall, there was no difference in remission rates and progression-free survival rates with or without CNS disease.

Active CNS disease at relapse and/or infusion. › A single-center report analyzed 195 sequential patients treated with 4-1BB CD19-targeted CAR T cells, 66 of whom had CNS disease (43 with isolated CNS disease, 23 with combined bone marrow/CNS disease).[186]

Patients with isolated CNS involvement had an RFS rate at 2 years of 66% (95% CI, 52%–82%), compared with 58% (95% CI, 50%–68%) for patients with bone marrow involvement (P = .15).

Active CNS disease at relapse and/or infusion. › A single-center report analyzed 195 sequential patients treated with 4-1BB CD19-targeted CAR T cells, 66 of whom had CNS disease (43 with isolated CNS disease, 23 with combined bone marrow/CNS disease).[186]

Ninety-eight percent of patients were treated before their infusion for their CNS disease and reached CNS1 or CNS2 status at the time of CAR T-cell treatment. Patients with symptomatic/progressive CNS disease were not treated until the disease was controlled and stable.

Active CNS disease at relapse and/or infusion.

A retrospective report examined the outcomes of 184 patients who were treated with tisagenlecleucel at 15 U.S. institutions. In this series, patients were referred for CAR T-cell infusion for marrow-only disease (n = 129), CNS disease (n = 40; either isolated [n = 23] or combined marrow/CNS disease [n = 17]), and non-CNS EMD (n = 15; 6 patients with isolated EMD and 9 with marrow involvement). All but one patient with CNS disease received tisagenlecleucel after one or more relapses (none had previously underwent transplant), whereas 29 of the marrow-only patients (22%) received infusions in first CR, 10 of whom (7.8%) had previously underwent transplant.[187]

Active CNS disease at relapse and/or infusion. › A retrospective report examined the outcomes of 184 patients who were treated with tisagenlecleucel at 15 U.S. institutions. In this series, patients were referred for CAR T-cell infusion for marrow-only disease (n = 129), CNS disease (n = 40; either isolated [n = 23] or combined marrow/CNS disease [n = 17]), and non-CNS EMD (n = 15; 6 patients with isolated EMD and 9 with marrow involvement). All but one patient with CNS disease received tisagenlecleucel after one or more relapses (none had previously underwent transplant), whereas 29 of the marrow-only patients (22%) received infusions in first CR, 10 of whom (7.8%) had previously underwent transplant.[187]

In patients referred to receive tisagenlecleucel for CNS disease (n = 40), 31 (78%) were already CNS-negative at the time of infusion, and 88% (35 of 40) were in CR at day 28 after infusion. For patients with non-CNS EMD, 10 of 15 (66%) were in CR at day 28.

Active CNS disease at relapse and/or infusion. › A retrospective report examined the outcomes of 184 patients who were treated with tisagenlecleucel at 15 U.S. institutions. In this series, patients were referred for CAR T-cell infusion for marrow-only disease (n = 129), CNS disease (n = 40; either isolated [n = 23] or combined marrow/CNS disease [n = 17]), and non-CNS EMD (n = 15; 6 patients with isolated EMD and 9 with marrow involvement). All but one patient with CNS disease received tisagenlecleucel after one or more relapses (none had previously underwent transplant), whereas 29 of the marrow-only patients (22%) received infusions in first CR, 10 of whom (7.8%) had previously underwent transplant.[187]

The 12-month RFS rate was 59.4% for patients with marrow-only disease, 59.4% for patients with CNS disease (isolated or combined), and 50% for those with non-CNS EMD (isolated or combined) (P = .92).

Active CNS disease at relapse and/or infusion. › A retrospective report examined the outcomes of 184 patients who were treated with tisagenlecleucel at 15 U.S. institutions. In this series, patients were referred for CAR T-cell infusion for marrow-only disease (n = 129), CNS disease (n = 40; either isolated [n = 23] or combined marrow/CNS disease [n = 17]), and non-CNS EMD (n = 15; 6 patients with isolated EMD and 9 with marrow involvement). All but one patient with CNS disease received tisagenlecleucel after one or more relapses (none had previously underwent transplant), whereas 29 of the marrow-only patients (22%) received infusions in first CR, 10 of whom (7.8%) had previously underwent transplant.[187]

In the CNS-disease cohort, there was no significant difference in 12-month RFS between patients with isolated CNS disease and those with combined CNS and marrow disease (P = .63).

Active CNS disease at relapse and/or infusion. › A retrospective report examined the outcomes of 184 patients who were treated with tisagenlecleucel at 15 U.S. institutions. In this series, patients were referred for CAR T-cell infusion for marrow-only disease (n = 129), CNS disease (n = 40; either isolated [n = 23] or combined marrow/CNS disease [n = 17]), and non-CNS EMD (n = 15; 6 patients with isolated EMD and 9 with marrow involvement). All but one patient with CNS disease received tisagenlecleucel after one or more relapses (none had previously underwent transplant), whereas 29 of the marrow-only patients (22%) received infusions in first CR, 10 of whom (7.8%) had previously underwent transplant.[187]

Grade 3 or 4 neurotoxicity was observed in 3 of 40 patients (7.5%) in the CNS-disease cohort, compared with 9 of 129 patients (7%) with marrow-only disease. None of the patients with active CNS disease at the time of infusion experienced grade 3 or 4 neurotoxicity.

Active CNS disease at relapse and/or infusion.

A second multicenter report reviewed 55 patients with relapses involving the CNS (isolated or combined with bone marrow) who were treated with either a CD28-based institutional CAR (n = 12) or tisagenlecleucel (4-1BB vector, n = 43).[188]

Active CNS disease at relapse and/or infusion. › A second multicenter report reviewed 55 patients with relapses involving the CNS (isolated or combined with bone marrow) who were treated with either a CD28-based institutional CAR (n = 12) or tisagenlecleucel (4-1BB vector, n = 43).[188]

Remission was achieved in 92% of children who received CD28-based CAR T cells and 93% of children who received 4-1BB–based CAR T cells.

Active CNS disease at relapse and/or infusion. › A second multicenter report reviewed 55 patients with relapses involving the CNS (isolated or combined with bone marrow) who were treated with either a CD28-based institutional CAR (n = 12) or tisagenlecleucel (4-1BB vector, n = 43).[188]

Of 11 children who received CD28-based CAR T cells and achieved a CR, 9 underwent HSCT. Seven of these nine patients survived relapse free.

Active CNS disease at relapse and/or infusion. › A second multicenter report reviewed 55 patients with relapses involving the CNS (isolated or combined with bone marrow) who were treated with either a CD28-based institutional CAR (n = 12) or tisagenlecleucel (4-1BB vector, n = 43).[188]

None of the 40 patients who were treated with the 4-1BB–based CAR T cells (tisagenlecleucel) and achieved a CR had a planned HSCT. Nineteen of these patients experienced relapses, 12 of whom had CNS relapses.

Active CNS disease at relapse and/or infusion. › A second multicenter report reviewed 55 patients with relapses involving the CNS (isolated or combined with bone marrow) who were treated with either a CD28-based institutional CAR (n = 12) or tisagenlecleucel (4-1BB vector, n = 43).[188]

Patients who received tisagenlecleucel for an isolated CNS relapse had a high incidence of subsequent CNS relapse (6 of 8 patients).

For non-CNS EMD, available data are limited.

For non-CNS EMD, available data are limited.

The report of 195 patients above compared CNS EMD, non-CNS EMD, and bone marrow–only disease. No differences in OS and RFS were noted between the groups.[186]

For non-CNS EMD, available data are limited.

In contrast, a large retrospective analysis found that active EMD at infusion was independently associated with worse EFS (HR, 1.9; P = .01).[189]

For non-CNS EMD, available data are limited.

A separate analysis found that in 15 patients with non-CNS EMD, 10 achieved a CR, and 6 of the 10 patients subsequently relapsed. Consequently, only 4 of 15 patients remained event-free during the follow-up period.[187]

For non-CNS EMD, available data are limited.

A retrospective analysis from the NCI identified limitations in eradication of non-CNS EMD with CAR T cells, despite concurrent marrow responses, highlighting the important role of positron emission tomography scans for monitoring.[190]