Contributions
Abstract: S834
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 12:00 - 12:15
Location: Room A8
Background
Several pre-clinical and clinical studies revealed the potential of adoptive immunotherapy with alloreactive, natural-Killer (NK) cells in acute myeloid leukemia (AML) patients. Indeed, adoptively transferred NK cells can be successfully expanded in vivo and significantly impact on leukemic cells killing.
Aims
Aim of this work is to establish the impact on long-term survival and relapse rate of adoptive immunotherapy with alloreactive NK cells in a cohort of AML patients, who had been infused with alloreactive NK cells in CR, as post-consolidation therapy.
Methods
Seventeen AML patients, with a median age of 64 years (range 53-73), were enrolled in our study. Patients were in first complete remission (CR) after standard chemotherapy regimens and were unfit for allogeneic stem cell transplantation (ASCT). Patients in morphologic or better CR with an haploidentical KIR-L–mismatched donor, received NK cells after an immunosuppressive chemotherapy regimen based on fludarabine 25 mg/mq from day 7 to 3 and cyclophosphamide 4 g/mq on day 2. Two days after cyclophosphamide administration, patients received the NK cell infusion (day 0), which was followed by subcutaneous administration of IL-2 (10x106 IU/day, 3 times weekly) for 2 weeks (6 doses total). To correlate donor NK cell activity with clinical response, donor NK cells were assessed before and after infusion.
Results
As previously reported, NK cell infusion was well-tolerated and no signs of GVHD were described. The median follow-up is now extended to 55.5 months (range 6-125 months) vs 22.5 (range 6-68 months) in the original publication. Eight out of 16 evaluable patients (50%) are alive disease-free. Among relapsing patients (8 of 16), median time to relapse was 9 months (range 5-51 months). Three of the relapsed patients maintained a prolonged CR for 15, 24 and 51 months, respectively. Among them, the patient relapsing after 51 months received a second NK infusion, thus obtaining a second CR. All patients treated with molecular disease achieved molecular CR. Based on these data, 11 of 16 (69%) patients were considered as responders, whereas 5 of 16 (31%) were non-responders. These long-term clinical results were compared with the outcome of patients from a historical control cohort, treated with standard chemotherapy regimen and who did not receive NK immunotherapy. In the latter group, 14 out of 15 patients (93%) relapsed, with a median time to relapse of 11 months (range 3-79). Due to the low numbers of evaluable patients, the difference in terms of DFS between the two groups of patients is not statistically significant, although a trend toward an increase of DFS for patients who received NK infusion may be observed. In agreement with our previous work, the predictive impact of higher alloreactive NK donor repertoire on clinical outcome was confirmed also when a longer-follow up was evaluated.
Conclusion
In conclusion, adoptively transferred alloreactive NK cells have the potential to induce prolonged control of AML in the non transplant setting. Moreover, the composition of NK graft in terms of frequency of alloreactive NK cells is likely to influence the long-term clinical response.
Session topic: 26. Gene therapy, cellular immunotherapy and vaccination - Clinical
Keyword(s): Acute Myeloid Leukemia, Natural killer, Outcome
Abstract: S834
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 12:00 - 12:15
Location: Room A8
Background
Several pre-clinical and clinical studies revealed the potential of adoptive immunotherapy with alloreactive, natural-Killer (NK) cells in acute myeloid leukemia (AML) patients. Indeed, adoptively transferred NK cells can be successfully expanded in vivo and significantly impact on leukemic cells killing.
Aims
Aim of this work is to establish the impact on long-term survival and relapse rate of adoptive immunotherapy with alloreactive NK cells in a cohort of AML patients, who had been infused with alloreactive NK cells in CR, as post-consolidation therapy.
Methods
Seventeen AML patients, with a median age of 64 years (range 53-73), were enrolled in our study. Patients were in first complete remission (CR) after standard chemotherapy regimens and were unfit for allogeneic stem cell transplantation (ASCT). Patients in morphologic or better CR with an haploidentical KIR-L–mismatched donor, received NK cells after an immunosuppressive chemotherapy regimen based on fludarabine 25 mg/mq from day 7 to 3 and cyclophosphamide 4 g/mq on day 2. Two days after cyclophosphamide administration, patients received the NK cell infusion (day 0), which was followed by subcutaneous administration of IL-2 (10x106 IU/day, 3 times weekly) for 2 weeks (6 doses total). To correlate donor NK cell activity with clinical response, donor NK cells were assessed before and after infusion.
Results
As previously reported, NK cell infusion was well-tolerated and no signs of GVHD were described. The median follow-up is now extended to 55.5 months (range 6-125 months) vs 22.5 (range 6-68 months) in the original publication. Eight out of 16 evaluable patients (50%) are alive disease-free. Among relapsing patients (8 of 16), median time to relapse was 9 months (range 5-51 months). Three of the relapsed patients maintained a prolonged CR for 15, 24 and 51 months, respectively. Among them, the patient relapsing after 51 months received a second NK infusion, thus obtaining a second CR. All patients treated with molecular disease achieved molecular CR. Based on these data, 11 of 16 (69%) patients were considered as responders, whereas 5 of 16 (31%) were non-responders. These long-term clinical results were compared with the outcome of patients from a historical control cohort, treated with standard chemotherapy regimen and who did not receive NK immunotherapy. In the latter group, 14 out of 15 patients (93%) relapsed, with a median time to relapse of 11 months (range 3-79). Due to the low numbers of evaluable patients, the difference in terms of DFS between the two groups of patients is not statistically significant, although a trend toward an increase of DFS for patients who received NK infusion may be observed. In agreement with our previous work, the predictive impact of higher alloreactive NK donor repertoire on clinical outcome was confirmed also when a longer-follow up was evaluated.
Conclusion
In conclusion, adoptively transferred alloreactive NK cells have the potential to induce prolonged control of AML in the non transplant setting. Moreover, the composition of NK graft in terms of frequency of alloreactive NK cells is likely to influence the long-term clinical response.
Session topic: 26. Gene therapy, cellular immunotherapy and vaccination - Clinical
Keyword(s): Acute Myeloid Leukemia, Natural killer, Outcome