Low incidence of hepatitis B virus reactivation in patients with hematological malignancies receiving novel anticancer drugs: A report from a high epidemic area and literature review.

BACKGROUND: More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. METHODS: HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. RESULTS: Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. CONCLUSION: Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.

L-Type Cav 1.2 Calcium Channel-α-1C Regulates Response to Rituximab in Diffuse Large B-Cell Lymphoma.

PURPOSE: One third of patients with diffuse large B-cell lymphoma (DLBCL) succumb to the disease partly due to rituximab resistance. Rituximab-induced calcium flux is an important inducer of apoptotic cell death, and we investigated the potential role of calcium channels in rituximab resistance. EXPERIMENTAL DESIGN: The distinctive expression of calcium channel members was compared between patients sensitive and resistant to rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone (RCHOP) regimen. The observation was further validated through mechanistic in vitro and in vivo studies using cell lines and patient-derived xenograft mouse models. RESULTS: A significant inverse correlation was observed between CACNA1C expression and RCHOP resistance in two independent DLBCL cohorts, and CACNA1C expression was an independent prognostic factor for RCHOP resistance after adjusting for International Prognostic Index, cell-of-origin classification, and MYC/BCL2 double expression. Loss of CACNA1C expression reduced rituximab-induced apoptosis and tumor shrinkage. We further demonstrated direct interaction of CACNA1C with CD20 and its role in CD20 stabilization. Functional modulators of L-type calcium channel showed expected alteration in rituximab-induced apoptosis and tumor suppression. Furthermore, we demonstrated that CACNA1C expression was directly regulated by miR-363 whose high expression is associated with worse prognosis in DLBCL. CONCLUSIONS: We identified the role of CACNA1C in rituximab resistance, and modulating its expression or activity may alter rituximab sensitivity in DLBCL.