Lebanese Real-World Experience in Treating Multiple Myeloma: A Multicenter Retrospective Study.

OBJECTIVE: The present retrospective multicenter study aims at documenting characteristics of multiple myeloma (MM) patients and the effect of autologous stem cell transplant (ASCT) on survival. METHODS: A total of 134 adult patients initiating any new MM therapy from January 2002 till December 2019 were included. Enrollment was stratified by disease subtype, induction protocol and transplant status. The characteristics and survival outcomes were recorded. RESULTS: Mean age at diagnosis was 61.91 ± 10.83 years, with 62.7% male patients. Regarding the prognostic MM International Staging System (ISS), stage 3 was the most common at diagnosis with 50.8% of patients followed by stage 1 (25.4%) and stage 2 (23.8%). Maintenance treatment was given in 88.5% of the patients. 24.6% patients were transplanted, 41% were not and the remaining were unknown or still in induction. 86.1% of patients were alive at data cut off. A significantly higher mean progression free survival (PFS) was found in transplant patients (p=0.016). Using cox regression, creatinine >2 mg/dl (HR3.78) and hypercalcemia >11 mg/dl (HR=6.48) were significantly associated with a shorter PFS1. A significantly shorter overall survival (OS) was associated with hypercalcemia (HR=6.58), as well as male gender though not statistically significant in the latter. Difference in survival distributions by treatment was not statistically significant (bortezomib thalidomide dexamethasone (VTD) (p=0.211), bortezomib cyclophosphamide dexamethasone (VCD) (p=0.111) or bortezomib Revlimid dexamethasone (VRD) (p=0.312)). The interaction between ISS stage on diagnosis and transplant was not significantly associated with the overall survival. CONCLUSION: The results of our retrospective study are in conformity with international data emphasizing the role of transplant in the treatment algorithm of newly diagnosed transplant-eligible multiple myeloma patients.

Negativation of PD-L1 Postoperatively in Initially Inoperable Stage III Non-Small Cell Lung Cancer Treated with Pembrolizumab: Two Case Reports.

Stage III non-small cell lung cancer is a border line stage between localized and metastatic disease. PDL-1 is gaining an important role in the therapeutic arsenal of lung cancer, the most frequent cancer worldwide. We report for the first time a negativation of PDL-1 status in 2 cases of stage IIIA NSCLC with conversion to operable disease after using immunotherapy. The first patient was a 59-year old female diagnosed incidentally to have stage IIIA inoperable NSCLC that was treated with combination chemo-immunotherapy, and converted to operable disease with a negative PD-L1 in the postoperative setting. The second case is that of a 56-year old male that also had an inoperable stage IIIA NSCLC treated with chemotherapy first line followed by pembrolizumab at progression, then operated after surgical conversion, with negative PD-L1 postoperatively. In front of these findings, further work should be done to elucidate if the reverse of the PDL-1 status and the conversion to operability were due to the use of immunotherapy or to an incidental finding. If confirmed, it may have a therapeutic impact.

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis.

The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX­2 (HEL cell line) or not (K562 cell line). Moreover, we made use of COX­2 cDNA to overexpress COX­2 in K562 cells. In light of the reported chemopreventive and chemosensitive effects of natural products on various tumor cells and animal models, we postulated that our Bl extract may mediate their effects through apoptosis induction with suppression of cell survival pathways. Our study is the first report on the specific examination of intrinsic apoptosis and Akt/NF-κB/COX­2 pathways in human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl extract treatment on K562 cells was observed resulting in activation of the late markers of apoptosis with caspase-3 activation, PARP cleavage and DNA fragmentation. Whereas, we showed that Bl extract reduced significantly expression of COX­2 by a dose-dependent manner in HEL and K562 (COX­2+) cells. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of Bl extract in human erythroleukemia cells. We observed that the Bl extract is clearly more active than the berberine alone on the induction of DNA fragmentation in human erythro-leukemia cells.