Abstract 1054P
Background
Conditioning lymphodepletive chemotherapy is an essential part of adoptive cell therapy (ACT) of cancer. ACT with tumor infiltrating lymphocytes (TILs) is in phase III clinical testing for malignant melanoma (MM) and with the advance into other cancer diagnoses it is important to evaluate the bone marrow (BM) toxicity of this therapy in patients with different therapeutic backgrounds.
Methods
Patients were treated in two clinical ACT trials (ovarian cancer NCT03287674 or across cancer types NCT03296137). All patients received identical regime of lymphodepleting chemotherapy consisting of 2 days of cyclophosphamide (60 mg/kg) followed by 5 days of fludarabine (25 mg/m2) before TILs. In addition, the treatment schedule included a short course of check point inhibitors and low dose interleukin-2.
Results
Thirty-one patients with 14 different cancer diagnoses including 6 patients with MM were treated between 2017 and 2019. All suffered grade 3-4 myelosuppression and the median length of neutropenia, anemia and thrombocytopenia were 8 days (range: 4-15), 12 days (range: 0-28) and 7 days (range: 0-19) respectively. Most patients required multiple blood- and platelet transfusions. All patients recovered from BM suppression without stem cell support, but many suffered from recurrent neutropenia, lymphopenia or thrombocytopenia following discharge. The duration of anemia, but not neutropenia and thrombocytopenia, was significantly related to the intensity of earlier chemotherapy regimens.
Conclusions
In conclusion, the conditioning chemotherapy was safe and tolerated in all melanoma and non-melanoma patients and induced a reversible myelosuppression. Our data show that the treatment history affects the severity of the BM toxicity during conditioning chemotherapy but without rendering it unsafe to use lymphodepleting chemotherapy in connection with ACT.
Clinical trial identification
NCT03287674; NCT03296137.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Knæk Cancer.
Disclosure
All authors have declared no conflicts of interest.