Patient characteristics and response to therapy
. | . | . | . | . | . | . | γδ T-cell Proliferation∥ . | . | . | |
|---|---|---|---|---|---|---|---|---|---|---|
| Patient . | Age, y/sex . | Diagnosis/stage* . | Prior therapy (no. of cycles)† . | Off therapy, mo‡ . | IL-2 dose level (no. of cycles) . | Side effects§ . | In vitro . | In vivo . | Response¶ . | |
| Cohort A | ||||||||||
| 1A | 83/M | MM/III | MP (15) | 2 | 0.25-0.5 × 106 IU/m2 (2) | − | − | − | PD | |
| 2A | 79/M | CLL/IV | CLB (10) | 11 | 0.25-3 × 106 IU/m2 (6) | F(1), T(3) | +♯ | − | SD | |
| 3A | 67/F | CLL/IV | PM (10), CLB (5) | 2 | 0.25-0.5 × 106 IU/m2 (2) | I(1), F(1), T(2) | − | − | PD | |
| 4A | 57/M | IC/IV | CLB/P (24), LR (30 Gy) | 14 | 0.5 × 106 IU/m2 (1) | T(2) | − | − | PD | |
| 5A | 76/F | MM/III | MP (9) | 10 | 0.5 × 106 IU/m2 (1) | I(2), F(2), T(2) | − | ND | NE | |
| 6A | 63/F | CLL/IV | CLB/P (25), MCP (6), F (12), R (4) | 5 | 0.5 × 106 IU/m2 (1) | F(2), I(2) | ND | − | PD | |
| 7A | 68/M | CLL/IV | CLB/P (4), COP (6), CLB (12) | 2 | 1-2 × 106 IU/m2 (2) | I(2), F(2), T(3) | ND | − | PD | |
| 8A | 66/M | MM/III | MP (15), VID (6) | 2 | 1 × 106 IU/m2 (1) | − | ND | − | PD | |
| 9A | 58/M | MZL/III | MCP (6), TBI/CY + PBSCT (1) | 29 | 1 × 106 IU/m2 (1) | F(2), T(2) | ND | − | PD | |
| 10A | 79/F | MM/III | CHOP (2), LR (50 Gy) | 10 | 2-3 × 106 IU/m2 (2) | F(1), T(2) | ND | − | PD | |
| Cohort B | ||||||||||
| 1B | 73/M | MM/III | MP (2), VID (6) | 3 | 0.25 × 106 IU/m2 (1) | − | + | − | PD | |
| 2B | 59/M | MM/III | MP (16), VID (6), HD-M + PBSCT (1), IFN | 2 | 0.25 × 106 IU/m2 (2) | T(2) | + | − | PD | |
| 3B | 52/M | FCL/IV | MCP (4), CHOP (2), Dexa-BEAM (2), IFN, LR (44 Gy), I131-R | 4 | 0.25 × 106 IU/m2 (1) | F(1), T(2) | + + | − | PD | |
| 4B | 43/F | FCL/III | TNI (49 Gy) | 24 | 0.5-1 × 106 IU/m2 (4) | F(2), T(2) | + + + | + + + | SD | |
| 5B | 57/M | MM/II | VID (4) | 2 | 0.5-2 × 106 IU/m2 (9) | F(1), T(2) | + + + | + | PR | |
| 6B | 36/F | MM/II | LR (30 Gy) | 3 | 0.5 × 106 IU/m2 (1) | F(1), S(1) | + | + + | PD | |
| 7B | 46/M | MZL/IV | TNI (44 Gy) | 29 | 1 × 106 IU/m2 (4) | F(2), T(2) | + + + | − | SD | |
| 8B | 51/F | FCL/IV | COP (10), LR (30 Gy), MCP (4) | 48 | 2 × 106 IU/m2 (4) | F(1), T(2), S(2) | + + + | + | PR | |
| 9B | 55/M | FCL/III | CHOP (4), Dexa-BEAM (2), TBI/CY + PBSCT (1), LR (30 Gy) | 6 | 1-2 × 106 IU/m2 (8) | F(1) | + | + | PR | |
. | . | . | . | . | . | . | γδ T-cell Proliferation∥ . | . | . | |
|---|---|---|---|---|---|---|---|---|---|---|
| Patient . | Age, y/sex . | Diagnosis/stage* . | Prior therapy (no. of cycles)† . | Off therapy, mo‡ . | IL-2 dose level (no. of cycles) . | Side effects§ . | In vitro . | In vivo . | Response¶ . | |
| Cohort A | ||||||||||
| 1A | 83/M | MM/III | MP (15) | 2 | 0.25-0.5 × 106 IU/m2 (2) | − | − | − | PD | |
| 2A | 79/M | CLL/IV | CLB (10) | 11 | 0.25-3 × 106 IU/m2 (6) | F(1), T(3) | +♯ | − | SD | |
| 3A | 67/F | CLL/IV | PM (10), CLB (5) | 2 | 0.25-0.5 × 106 IU/m2 (2) | I(1), F(1), T(2) | − | − | PD | |
| 4A | 57/M | IC/IV | CLB/P (24), LR (30 Gy) | 14 | 0.5 × 106 IU/m2 (1) | T(2) | − | − | PD | |
| 5A | 76/F | MM/III | MP (9) | 10 | 0.5 × 106 IU/m2 (1) | I(2), F(2), T(2) | − | ND | NE | |
| 6A | 63/F | CLL/IV | CLB/P (25), MCP (6), F (12), R (4) | 5 | 0.5 × 106 IU/m2 (1) | F(2), I(2) | ND | − | PD | |
| 7A | 68/M | CLL/IV | CLB/P (4), COP (6), CLB (12) | 2 | 1-2 × 106 IU/m2 (2) | I(2), F(2), T(3) | ND | − | PD | |
| 8A | 66/M | MM/III | MP (15), VID (6) | 2 | 1 × 106 IU/m2 (1) | − | ND | − | PD | |
| 9A | 58/M | MZL/III | MCP (6), TBI/CY + PBSCT (1) | 29 | 1 × 106 IU/m2 (1) | F(2), T(2) | ND | − | PD | |
| 10A | 79/F | MM/III | CHOP (2), LR (50 Gy) | 10 | 2-3 × 106 IU/m2 (2) | F(1), T(2) | ND | − | PD | |
| Cohort B | ||||||||||
| 1B | 73/M | MM/III | MP (2), VID (6) | 3 | 0.25 × 106 IU/m2 (1) | − | + | − | PD | |
| 2B | 59/M | MM/III | MP (16), VID (6), HD-M + PBSCT (1), IFN | 2 | 0.25 × 106 IU/m2 (2) | T(2) | + | − | PD | |
| 3B | 52/M | FCL/IV | MCP (4), CHOP (2), Dexa-BEAM (2), IFN, LR (44 Gy), I131-R | 4 | 0.25 × 106 IU/m2 (1) | F(1), T(2) | + + | − | PD | |
| 4B | 43/F | FCL/III | TNI (49 Gy) | 24 | 0.5-1 × 106 IU/m2 (4) | F(2), T(2) | + + + | + + + | SD | |
| 5B | 57/M | MM/II | VID (4) | 2 | 0.5-2 × 106 IU/m2 (9) | F(1), T(2) | + + + | + | PR | |
| 6B | 36/F | MM/II | LR (30 Gy) | 3 | 0.5 × 106 IU/m2 (1) | F(1), S(1) | + | + + | PD | |
| 7B | 46/M | MZL/IV | TNI (44 Gy) | 29 | 1 × 106 IU/m2 (4) | F(2), T(2) | + + + | − | SD | |
| 8B | 51/F | FCL/IV | COP (10), LR (30 Gy), MCP (4) | 48 | 2 × 106 IU/m2 (4) | F(1), T(2), S(2) | + + + | + | PR | |
| 9B | 55/M | FCL/III | CHOP (4), Dexa-BEAM (2), TBI/CY + PBSCT (1), LR (30 Gy) | 6 | 1-2 × 106 IU/m2 (8) | F(1) | + | + | PR | |
MM indicates multiple myeloma; CLL, chronic lymphocytic leukemia; IC, immunocytoma; MZL, mantle zone lymphoma. Staging according to Durie and Salmon (MM), Rai (CLL), Ann-Arbor (IC; MZL).
MP indicates melphalan/prednisone; CLB, chlorambucil; PM, prednimustine; COP, cyclophosphamide/vincristine/prednisone; VID, vincristine/idarubicin/dexamethasone; MCP, mitoxantrone/chlorambucil/prednisone; CHOP, cyclophosphamide/vincristine/prednisone; F, fludarabine; R, rituximab; TBI/CY, total body irradiation/high-dose cyclophosphamide followed by peripheral blood stem cell transplantation (PBSCT); LR, local radiotherapy (dose); I131-R; radioimmunotherapy with iodine131-rituximab; Dexa-BEAM, dexamethasone/carmustine/etoposide/cytarabine/melphalan; HD-M, high-dose melphalan followed by PBSCT; TNI, total nodal irradiation (dose); and IFN, INF-α (maintenance therapy).
Months between last chemotherapy/radiotherapy and first pamidronate/IL-2 treatment.
T indicates thrombophlebitis; F, fever; S, skin-erythema; I, infection; (2) WHO grade 2.
In vitro results represent percentages of control culture according to the following calculation: (γδ T-cell number in pamidronate/IL-2 culture)−(γδ T-cell number in medium/IL-2)/(γδ T-cell number in medium/IL-2) × 100. In vivo results represent percentage of increase according to the following calculation: (Vy9δ2 T-cell number on day 8 after pamidronate/IL-2 infusion)−(Vγ9δ2 T-cell number before treatment)/(Vγ9δ2 T-cell number before treatment) × 100. − Indicates <20%; +, 20% to 100%; + +, >100% to 200%; + + +, >200% increase of γδ T-cell number; ND, not done.
SD indicates stable disease; PR, partial remission; PD, progressive disease; NE, not evaluable.
No absolute counts are available; however, percentage of γδ T cells increased from 7% to 19.5%.