Efficacy of host-dendritic cell vaccinations with or without minor histocompatibility antigen loading, combined with donor lymphocyte infusion in multiple myeloma patients.

Donor lymphocyte infusions (DLI) can induce durable remissions in multiple myeloma (MM) patients, but this occurs rather infrequently. As the graft-versus-tumor (GvT) effect of DLI depends on the presence of host-dendritic cells (DCs), we tested in a phase I/II trial whether the efficacy of DLI could be improved by simultaneous vaccination with host-DCs. We also analyzed the possibility of further improving the GvT effect by loading the DCs with peptides of mismatched hematopoietic cell-specific minor histocompatibility antigens (mHags). Fifteen MM patients not responding to a first DLI were included. Eleven patients could be treated with a second equivalent dose DLI combined with DC vaccinations, generated from host monocytes (moDC). For four patients, the DC products did not meet the quality criteria. In four of the treated patients the DCs were loaded with host mHag peptides. Toxicity was limited and no acute GvHD occurred. Most patients developed objective anti-host T-cell responses and in one patient a distinct mHag-specific T-cell response accompanied a temporary clinical response. These findings confirm that DLI combined with host-DC vaccination, either unloaded or loaded with mHag peptides, is feasible, safe and capable of inducing host-specific T-cell responses. The limited clinical effects may be improved by developing more immunogenic DC products or by combining this therapy with immune potentiating modalities like checkpoint inhibitors.

Carcinomatous meningitis in cancer of the uterine cervix.

Carcinomatous meningitis is extremely rare in cervical cancer. The diagnosis of carcinomatous meningitis is a difficult one when clinical symptoms are limited and radiographic imaging is normal. Demonstration of malignant cells in the cerebrospinal fluid remains the gold standard to establish the diagnosis. For patients without bulky disease who can be treated with radiotherapy, standard treatment for carcinomatous meningitis is chemotherapy, which may be administered intrathecally. Despite the poor prognosis, treatment may result in effective palliation. We describe a 54-year-old patient who was diagnosed with carcinomatous meningitis in the course of metastatic cervical cancer and who responded to administration of intrathecal methotrexate.