Abstract 164P
Background
Lurbinectedin (Lur) is currently investigated in pre-treated patients (pts) with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). According to pre-clinical models, lur has the ability to induce anticancer immune responses. The immune-modulatory functions of lur in thoracic cancer pts have not been investigated yet.
Methods
SCLC and MPM pts treated with lurbinectedin in the context of a named patient program at the Erasmus Medical Center, Rotterdam, NL were prospectively included. Comprehensive immune cell profiling by multicolor flow-cytometry was performed on screening and on treatment (after 2 cycles) peripheral blood samples.
Results
In total, 95 pts (43 SCLC and 52 MPM) were treated, mainly as ≥3-line of therapy. In the SCLC cohort, median (m) PFS was 1.5 months (95% CI: 1.4–3.0), and mOS was 7.0 months (95% CI: 4.7–not reached). In the MPM cohort, mPFS was 2.8 months (95% CI: 1.4–4.2), and mOS was 7.2 months (95% CI: 5.9–not reached). Immunological phenotyping was performed on 39 pts. Lur significantly reduced HLADR+CD56-CD14+CD16- cell frequencies, the classical monocyte subset, in both SCLC and MPM pts. SCLC pts with lower frequencies of classical monocytes before treatment also had a longer PFS. Lur significantly increased proliferation of CD4+, CD8+ T-cells (SCLC), and NK- and NKT-cells (SCLC and MPM). Treatment increased the proliferation of CD4+ central memory (TCM) and effector memory (TEM) T-cells and of CD8+ TEM cells among SCLC. In MPM, treatment increased more specifically the proliferation of CD4+ TEM cells, while CD8+ T-cells were not affected. Finally, lur induced a two-side alteration of the circulating T-cell phenotype, with upregulation of co-stimulatory receptors being counterbalanced by upregulation of co-inhibitory markers.
Conclusions
Lur confirms clinical activity in pre-treated SCLC and MPM pts. Our exploratory immunomonitoring study also shows that lur might have immune-modulatory functions through depletion of the classical monocyte subset, promotion of proliferation and phenotype shifting of anti-tumor immune cell populations. Therefore, lur might represent an interesting chemotherapy backbone for future immunotherapy combinations in SCLC and MPM.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.