(P 243) MYELOSUPPRESSION FOLLOWING LYMPHODEPLETING CHEMOTHERAPY AS PART OF ADOPTIVE CELL THERAPY FOR PATIENTS WITH PROGRESSIVE SOFT TISSUE SARCOMA AFTER STANDARD CHEMOTHERAPY

Objective: Adoptive cell transfer (ACT) therapies have shown impressive clinical results primarily in patients with melanoma and hematological cancers, but this field is also currently being investigated as a treatment for patients with sarcoma. A potential challenge could be the lymphodepleting chemotherapy that is used as part of ACT to potentiate the efficacy. While melanoma patients are usually naïve to chemotherapy, most sarcoma patients are heavily pretreated when entering ACT trials. It is therefore important to consider both short- and long-term effect on the bone marrow.

We have recently conducted a clinical trial with the combination of ACT using tumor-infiltrating lymphocytes (TILs) and injections of the oncolytic peptide LTX-315 (Lytix Biopharma). Here, we report data on bone marrow restoration both on short and long term.

Methods: Patients with metastatic soft-tissue sarcoma (STS) who had progression on a minimum of one systemic treatment were eligible for inclusion in the trial. Patients received up to five treatments over 2-3 weeks with intratumoral LTX-315 injections before resection of the treated tumor for in vitro TIL expansion. Prior to TIL infusion, patients received preparative lymphodepleting chemotherapy with two days of cyclophosphamide and five days of fludarabine phosphate. Following TIL infusion, patients received 14 days of subcutaneous IL-2.

Results: Four patients received the full treatment with both LTX-315 injections and ACT. Mean progression free survival was 22 weeks (range 10-30 weeks). All four patients had received doxorubicin-based chemotherapy prior to inclusion. One patient had received VIDE/VAI* prior to inclusion. In general, neutropenia lasted until day six, whereafter increasing platelets were seen (figure 1). During admission for ACT, patients received on median 3.5 blood transfusions and 4.5 platelet transfusion which is comparable to melanoma patients receiving similar treatment (table 1). One patient experienced neutropenia and thrombocytopenia following radiotherapy four months after completed ACT which could have been affected by the lymphodepleting chemotherapy six (figure 2).

* vincristine/ifosfamide/doxorubicin/etoposide; vincristine/actinomycin D/ifosfamide

Conclusion: These data demonstrates that bone marrow recovery following lymphodepleting chemotherapy in sarcoma patients is comparable to what is observed in melanoma patients. In one case, however, a patient experienced prolonged myelosuppression four months after treatment most likely due to the lymphodepleting chemotherapy.