Contributions
Abstract: S860
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 16:45 - 17:00
Location: Room A2
Background
Standard induction chemotherapy (7+3) for AML results in prolonged neutropenia with a high risk of infection. CLT-008 is an off-the-shelf human allogeneic myeloid progenitor cell (MPC) preparation manufactured by ex vivo culture expansion of CD34+ cells. Following infusion, MPCs are expected to home to bone marrow (BM) and produce neutrophils.
Aims
Study the effect of CLT-008 on the reduction of infections during AML induction therapy.
Methods
94 de novo AML subjects (age ≥55) receiving 7+3 induction therapy were randomized on Day 0 (first day of induction) to receive a regimen of CLT-008 (7.5x106 cells/Kg) on Day 9 + GCSF daily starting on Day 14 (intervention) or GCSF alone daily starting on Day 14 (control) until ANC recovery to ≥500/µL. The primary endpoint was days in a febrile episode (DFE) and secondary endpoints included clinically diagnosed (CDI) and microbiologically diagnosed (MDI) bacterial or fungal infection (adjudicated by a blinded independent committee), use of antimicrobials, and days in hospital (to Day 42). Data are reported for 2 periods: From infusion of CLT-008 on Day 9-28 and from 6 days after infusion of CLT-008 (1 day after start of GCSF) – Day 28 (denoted as Day 15-28). This is the period when CLT-008 derived neutrophils are likely to be circulating. Intervention and control subjects were evaluable if they received respectively CLT-008 or GCSF alone, were on study ≥28 days, and did not receive additional chemotherapy before Day 28. One-sided p-values are reported.
Results
The baseline characteristics, including mean age, mean WBC, and ECOG status were balanced between the intervention and control groups. The mean DFE during Day 9-28 in the intervention and control was 7.37 and 9.11 days respectively (p=0.099). The mean DFE for Day 15-28 was 3.24 and 4.77 days in the intervention vs. control respectively (p=0.057). The incidence of MDI or CDI during Day 9-28 was 33% vs 51% in the intervention vs. control, a decrease of 35% (p=0.058) and during Day 15-28 was 7.6% vs 28% in the intervention vs. control, a decrease of 73% (p=0.010).
Incidence of Subjects Receiving Antibacterial Agents
| Empiric therapy with IDSA Group 2a Intervention (N = 39) vs Controls (N = 39) | Antibacterial treatment of MDI/CDI Intervention (N=39) vs Control (N=39) |
Days 9-28 | 38% vs 54% p=0.084 | 38% vs 67% p=0.007 |
Days 15-28 | 31% vs 54% p=0.021 | 36% vs 64% p=0.007 |
a IDSA2: antimicrobials added to initial treatment of neutropenic fever due to suboptimal response to initial treatment.
Mean number of days in hospital were 27.1 vs 30.6 days in intervention vs. control groups (p=0.003). Remission rates and days to ANC recovery were similar in the two groups. Eleven subjects assessed for chimerism had CLT‑008 cells detected in peripheral blood (PB) on the day of infusion. Post infusion, chimerism was observed on day 13 or 14 in bone marrow in 5/6 subjects and in PB in 5/11 subjects between days 13 and 21 prior to ANC recovery. No infectious deaths were observed in the intervention group; there were two deaths attributed to pneumonia in the control group. CLT-008 was generally tolerated well.
Conclusion
The incidence of infections, use of antibacterial agents and days in hospital were decreased in subjects receiving CLT-008. Myeloid progenitors may provide a new option to reduce infections in AML patients undergoing induction therapy.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): AML, Induction, Infection, neutropenia
Abstract: S860
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 16:45 - 17:00
Location: Room A2
Background
Standard induction chemotherapy (7+3) for AML results in prolonged neutropenia with a high risk of infection. CLT-008 is an off-the-shelf human allogeneic myeloid progenitor cell (MPC) preparation manufactured by ex vivo culture expansion of CD34+ cells. Following infusion, MPCs are expected to home to bone marrow (BM) and produce neutrophils.
Aims
Study the effect of CLT-008 on the reduction of infections during AML induction therapy.
Methods
94 de novo AML subjects (age ≥55) receiving 7+3 induction therapy were randomized on Day 0 (first day of induction) to receive a regimen of CLT-008 (7.5x106 cells/Kg) on Day 9 + GCSF daily starting on Day 14 (intervention) or GCSF alone daily starting on Day 14 (control) until ANC recovery to ≥500/µL. The primary endpoint was days in a febrile episode (DFE) and secondary endpoints included clinically diagnosed (CDI) and microbiologically diagnosed (MDI) bacterial or fungal infection (adjudicated by a blinded independent committee), use of antimicrobials, and days in hospital (to Day 42). Data are reported for 2 periods: From infusion of CLT-008 on Day 9-28 and from 6 days after infusion of CLT-008 (1 day after start of GCSF) – Day 28 (denoted as Day 15-28). This is the period when CLT-008 derived neutrophils are likely to be circulating. Intervention and control subjects were evaluable if they received respectively CLT-008 or GCSF alone, were on study ≥28 days, and did not receive additional chemotherapy before Day 28. One-sided p-values are reported.
Results
The baseline characteristics, including mean age, mean WBC, and ECOG status were balanced between the intervention and control groups. The mean DFE during Day 9-28 in the intervention and control was 7.37 and 9.11 days respectively (p=0.099). The mean DFE for Day 15-28 was 3.24 and 4.77 days in the intervention vs. control respectively (p=0.057). The incidence of MDI or CDI during Day 9-28 was 33% vs 51% in the intervention vs. control, a decrease of 35% (p=0.058) and during Day 15-28 was 7.6% vs 28% in the intervention vs. control, a decrease of 73% (p=0.010).
Incidence of Subjects Receiving Antibacterial Agents
| Empiric therapy with IDSA Group 2a Intervention (N = 39) vs Controls (N = 39) | Antibacterial treatment of MDI/CDI Intervention (N=39) vs Control (N=39) |
Days 9-28 | 38% vs 54% p=0.084 | 38% vs 67% p=0.007 |
Days 15-28 | 31% vs 54% p=0.021 | 36% vs 64% p=0.007 |
a IDSA2: antimicrobials added to initial treatment of neutropenic fever due to suboptimal response to initial treatment.
Mean number of days in hospital were 27.1 vs 30.6 days in intervention vs. control groups (p=0.003). Remission rates and days to ANC recovery were similar in the two groups. Eleven subjects assessed for chimerism had CLT‑008 cells detected in peripheral blood (PB) on the day of infusion. Post infusion, chimerism was observed on day 13 or 14 in bone marrow in 5/6 subjects and in PB in 5/11 subjects between days 13 and 21 prior to ANC recovery. No infectious deaths were observed in the intervention group; there were two deaths attributed to pneumonia in the control group. CLT-008 was generally tolerated well.
Conclusion
The incidence of infections, use of antibacterial agents and days in hospital were decreased in subjects receiving CLT-008. Myeloid progenitors may provide a new option to reduce infections in AML patients undergoing induction therapy.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): AML, Induction, Infection, neutropenia