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.
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.
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.
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.
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All authors have declared no conflicts of interest.