Characteristics, salvage therapies, and outcomes of patients in the post-CAR19 extramedullary disease relapse cohort
| Case . | CAR19 product . | Pre-CAR19 immunotherapy . | Pre-CAR19 EMD, Y/N; site (diagnostic modality)∗ . | Post-CAR19 relapse sites (diagnostic modality)∗ . | CD19 immunophenotype of post-CAR19 relapse . | B-cell aplasia status at post-CAR relapse . | First salvage therapy . | Response to first salvage therapy . | Successfully bridged to definitive therapy (Y/N, outcome) . | Status at last follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|
| Isolated CNS | ||||||||||
| 1 | CTL019 | HCT | Y; CNS | CNS | + | B-cell aplasia | IT | NR | N; palliation only (PD) | Expired |
| 2 | CTL019 | None | Y; CNS | CNS | + | B-cell aplasia† | Cytotoxic chemotherapy + dasatinib | MRD-negative CR | Y; HCT‡ (CR) | Alive without disease |
| 3 | CTL019 | HCT | Y; CNS | CNS | + | B-cell aplasia | Rituximab, temozolomide with IT | NR | N; palliation only (PD) | Expired |
| 4 | Tisa-cel | None | Y; CNS | CNS with lymphomatous disease/(biopsy) | + | B-cell aplasia | Dexamethasone, IT, RT | NR | Y; HCT‡ (CR) | Alive without disease |
| 5 | huCART19 | HCT, CTL019 | N | CNS | + | B-cell aplasia | IT + RT | MRD-negative CR | N (PD)§ | Alive without disease |
| 6 | Tisa-cel | HCT, InO, Blina | Y; testicular, facial, scalp|| (biopsy) | CNS | Unk | Unk | Unk | Unk | Unk | Expired |
| 7 | CTL019 | HCT | Y; CNS + uterus|| (biopsy) | CNS | + | B-cell aplasia | CTL019 reinfusion | MRD-negative CR | Y; HCT¶ (CR, relapsed 5 mo later) | Expired |
| Combined BM and CNS | ||||||||||
| 8 | CTL019 | HCT | Y; CNS, ocular, scalp (Unk) | BM + CNS3 | + | B-cell aplasia | Cytotoxic chemotherapy | Unk | Unk | Expired |
| 9 | huCART19 | HCT | N | BM + CNS3 | – | B-cell aplasia | InO | MRD-negative CR | Y; HCT¶ (PD) | Expired |
| 10 | huCART19 | Tisa-cel | Y; CNS | BM + CNS3 | + | B-cell recovery | Ven, cytotoxic chemotherapy with IT | MRD-negative CR | Y; HCT‡ (CR, relapsed 9 mo later) | Alive without disease |
| 11 | Tisa-cel | None | Y; CNS | BM + CNS3 | + | B-cell recovery | huCART19 | NR | N (PD, NRM) | Expired |
| Non-CNS EMD | ||||||||||
| 12 | huCART19 | None | N | Breast (biopsy) | +/−# | B-cell aplasia | RT | MRD-negative CR | Y; HCT‡ (CR) | Alive without disease |
| 13 | huCART19 | None | N | Periorbital (biopsy) | + | B-cell recovery | Palliative RT | N/A | N; palliation only (PD) | Expired |
| 14 | huCART19 | HCT | Y; CNS + testicular, eyelid chloroma, sinus (biopsy) | Orbital (biopsy) | + | B-cell aplasia | Cytotoxic chemotherapy | NR | Y; huCART19 reinfusion with pembro (CR, relapse 11 mo later) | Expired |
| 15 | huCART19 | HCT, Blina | Y; axilla, epidural|| (biopsy) | Breast (biopsy) | + | B-cell recovery | RT | NR | Y; HCT¶ (NRM) | Expired |
| 16 | CTL019 | HCT | Y; CNS | Breast (biopsy) | + | B-cell aplasia | RT + CTL019 reinfusion | MRD-negative CR | Y; CTL019 reinfusion with pembro (CR, NRM 36 mo later) | Expired |
| 17 | CTL019 | HCT | Y - forehead (Unk) | Scalp, forehead (biopsy) | + | B-cell recovery | RT | MRD-negative CR | Y; HCT¶ (CR, relapse 15 mo later) | Expired |
| 18 | CTL019 | HCT | Y; CNS | Mediastinum (biopsy) | + | B-cell aplasia | CTL019 reinfusion | NR | N (PD) | Expired |
| 19 | CTL019 | HCT | N | Breast (biopsy) | Unk | B-cell aplasia | Unk | Unk | Unk | Expired |
| 20 | CTL019 | HCT | N | Forehead (imaging) | + | B-cell aplasia | CTL019 reinfusion | MRD-negative CR | Y; CTL019 reinfusion (same as salvage) (CR, relapse 1 mo later) | Expired |
| 21 | Tisa-cel | InO | N | Kidney (biopsy) | +∗∗ | B-cell aplasia | Aza/ven/GO | MRD-positive CR | N (PD) | Expired |
| Combined BM and non-CNS EMD | ||||||||||
| 22 | CTL019 | HCT | Y; CNS + parietal and occipital gyri chloromas (imaging) | BM + maxillary bones, sinus (biopsy) | – | B-cell aplasia | InO | MRD-negative CR | Y; HCT¶ (NRM) | Expired |
| 23 | CTL019 | HCT | Y; femur (Unk) | BM + iliac bones, spine/(imaging) | – | B-cell aplasia | CART22 | MRD-negative CR | Y; CART22 (CR) | Alive without disease |
| 24 | Tisa-cel | None | N | BM + periorbital mass/(imaging) | + | B-cell recovery | huCART19 | MRD-negative CR | Y; huCART19 and HCT‡ (CR) | Alive without disease |
| Case . | CAR19 product . | Pre-CAR19 immunotherapy . | Pre-CAR19 EMD, Y/N; site (diagnostic modality)∗ . | Post-CAR19 relapse sites (diagnostic modality)∗ . | CD19 immunophenotype of post-CAR19 relapse . | B-cell aplasia status at post-CAR relapse . | First salvage therapy . | Response to first salvage therapy . | Successfully bridged to definitive therapy (Y/N, outcome) . | Status at last follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|
| Isolated CNS | ||||||||||
| 1 | CTL019 | HCT | Y; CNS | CNS | + | B-cell aplasia | IT | NR | N; palliation only (PD) | Expired |
| 2 | CTL019 | None | Y; CNS | CNS | + | B-cell aplasia† | Cytotoxic chemotherapy + dasatinib | MRD-negative CR | Y; HCT‡ (CR) | Alive without disease |
| 3 | CTL019 | HCT | Y; CNS | CNS | + | B-cell aplasia | Rituximab, temozolomide with IT | NR | N; palliation only (PD) | Expired |
| 4 | Tisa-cel | None | Y; CNS | CNS with lymphomatous disease/(biopsy) | + | B-cell aplasia | Dexamethasone, IT, RT | NR | Y; HCT‡ (CR) | Alive without disease |
| 5 | huCART19 | HCT, CTL019 | N | CNS | + | B-cell aplasia | IT + RT | MRD-negative CR | N (PD)§ | Alive without disease |
| 6 | Tisa-cel | HCT, InO, Blina | Y; testicular, facial, scalp|| (biopsy) | CNS | Unk | Unk | Unk | Unk | Unk | Expired |
| 7 | CTL019 | HCT | Y; CNS + uterus|| (biopsy) | CNS | + | B-cell aplasia | CTL019 reinfusion | MRD-negative CR | Y; HCT¶ (CR, relapsed 5 mo later) | Expired |
| Combined BM and CNS | ||||||||||
| 8 | CTL019 | HCT | Y; CNS, ocular, scalp (Unk) | BM + CNS3 | + | B-cell aplasia | Cytotoxic chemotherapy | Unk | Unk | Expired |
| 9 | huCART19 | HCT | N | BM + CNS3 | – | B-cell aplasia | InO | MRD-negative CR | Y; HCT¶ (PD) | Expired |
| 10 | huCART19 | Tisa-cel | Y; CNS | BM + CNS3 | + | B-cell recovery | Ven, cytotoxic chemotherapy with IT | MRD-negative CR | Y; HCT‡ (CR, relapsed 9 mo later) | Alive without disease |
| 11 | Tisa-cel | None | Y; CNS | BM + CNS3 | + | B-cell recovery | huCART19 | NR | N (PD, NRM) | Expired |
| Non-CNS EMD | ||||||||||
| 12 | huCART19 | None | N | Breast (biopsy) | +/−# | B-cell aplasia | RT | MRD-negative CR | Y; HCT‡ (CR) | Alive without disease |
| 13 | huCART19 | None | N | Periorbital (biopsy) | + | B-cell recovery | Palliative RT | N/A | N; palliation only (PD) | Expired |
| 14 | huCART19 | HCT | Y; CNS + testicular, eyelid chloroma, sinus (biopsy) | Orbital (biopsy) | + | B-cell aplasia | Cytotoxic chemotherapy | NR | Y; huCART19 reinfusion with pembro (CR, relapse 11 mo later) | Expired |
| 15 | huCART19 | HCT, Blina | Y; axilla, epidural|| (biopsy) | Breast (biopsy) | + | B-cell recovery | RT | NR | Y; HCT¶ (NRM) | Expired |
| 16 | CTL019 | HCT | Y; CNS | Breast (biopsy) | + | B-cell aplasia | RT + CTL019 reinfusion | MRD-negative CR | Y; CTL019 reinfusion with pembro (CR, NRM 36 mo later) | Expired |
| 17 | CTL019 | HCT | Y - forehead (Unk) | Scalp, forehead (biopsy) | + | B-cell recovery | RT | MRD-negative CR | Y; HCT¶ (CR, relapse 15 mo later) | Expired |
| 18 | CTL019 | HCT | Y; CNS | Mediastinum (biopsy) | + | B-cell aplasia | CTL019 reinfusion | NR | N (PD) | Expired |
| 19 | CTL019 | HCT | N | Breast (biopsy) | Unk | B-cell aplasia | Unk | Unk | Unk | Expired |
| 20 | CTL019 | HCT | N | Forehead (imaging) | + | B-cell aplasia | CTL019 reinfusion | MRD-negative CR | Y; CTL019 reinfusion (same as salvage) (CR, relapse 1 mo later) | Expired |
| 21 | Tisa-cel | InO | N | Kidney (biopsy) | +∗∗ | B-cell aplasia | Aza/ven/GO | MRD-positive CR | N (PD) | Expired |
| Combined BM and non-CNS EMD | ||||||||||
| 22 | CTL019 | HCT | Y; CNS + parietal and occipital gyri chloromas (imaging) | BM + maxillary bones, sinus (biopsy) | – | B-cell aplasia | InO | MRD-negative CR | Y; HCT¶ (NRM) | Expired |
| 23 | CTL019 | HCT | Y; femur (Unk) | BM + iliac bones, spine/(imaging) | – | B-cell aplasia | CART22 | MRD-negative CR | Y; CART22 (CR) | Alive without disease |
| 24 | Tisa-cel | None | N | BM + periorbital mass/(imaging) | + | B-cell recovery | huCART19 | MRD-negative CR | Y; huCART19 and HCT‡ (CR) | Alive without disease |
Aza, azacitidine; Blina, blinatumomab; CART22, CD22-targeted CAR T-cell therapy; CR, complete remission; GO, gemtuzumab ozogamicin; huCART19, humanized CD19-targeted CAR T-cell therapy; InO, inotuzumab; IT, intrathecal chemotherapy; MRD, minimal residual disease as measured by multiparameter flow cytometry; N, no; N/A, not applicable; NR, no response; NRM, nonrelapse mortality; PD, progressive disease; pembro, pembrolizumab; RT, radiotherapy; Tisa-cel, tisagenlecleucel; Unk, unknown; ven, venetoclax; Y, yes.
Diagnostic modality for CNS disease was CSF sampling, unless otherwise noted.
Four percent to 5% hematogones present.
Represents a first HCT.
After attaining a CR, had PD, but achieved another CR with cytotoxic chemotherapy and has been maintained on blinatumomab since that time.
Active at CAR19 infusion.
Represents a second or later HCT.
CD19+ in most cells but negative in tumor areas with crushed artifact.
Although disease was CD19+, there was also concern for impending lineage switch.