Supplemental Digital Content is available in the text

Background. Daratumumab is an IgG kappa monoclonal antibody (mAB) against CD38 which is expressed on myeloma cells. It has recently been approved for treatment of patients with relapsed refractory multiple myeloma. Our objective was to identify the potential infectious complications associated with daratumumab use.Methods. We conducted a retrospective analysis of myeloma patients who received daratumumab at our institution from October 2015 to December 2016. Patients were divided into four groups based on administration regimen of daratumumab: (1) single agent with dexamethasone; (2) triple therapy with proteasome inhibitor (PI), immune-modulating drug (IMiD), mitogen-activated protein kinase (MEK) inhibitor or mAB; (3) quadruple therapy with IMiD + PI ± mAB or cyclophosphamide; (4) with high-dose chemotherapy. For each group, we evaluated the incidence of infection, neutropenia (defined as ANC <1,000), hospitalization, and 90-day survival.Results. A total of 171 patients (63% male, 37% female) were included in the study and received a total of 343 cycles of daratumumab. Median age was 68 years. A total of 151 infections occurred in 121 of the 343 cycles (40% bacterial; 52% viral). There was a significant association between development of infection and chemotherapy regimen used (χ 2 = 17, P ≤ 0.001). Patients developed neutropenia in 129 of 254 cycles (51%). There was a significant association between the development of neutropenia and chemotherapy regimen used (χ 2 = 43.51, P < 0.00001). Discontinuation of chemotherapy occurred in 65 cycles (19%), mainly due to progression of disease (54%). Eighty subjects (23%) required hospitalization, infection being the main cause (51%). Ninety-day survival was 91.8%.Conclusion. Infection is common among myeloma patients who receive daratumumab. Myeloma patients who receive daratumumab in conjunction with multidrug chemotherapy regimens have an increased risk of infection and neutropenia. Because daratumumab is given predominantly as outpatient therapy, a greater understanding of the potential immunomodulatory effects of daratumumab will lead to increased vigilance in identifying and treating clinically significant infections.

Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM). We measured serum Gal-1 levels in samples from patients with treatment demanding MM at the time of diagnosis (n=102) and after treatment (n=24) and examined associations of serum Gal-1 with clinicopathological information obtained from patient medical records, as well as data on bone marrow angiogenesis and the macrophage activation biomarkers soluble CD163 (sCD163) and soluble mannose receptor. Serum Gal-1 levels were not elevated in patients with MM at diagnosis compared with healthy donors (median values 8.48 vs 11.93 ng/mL, P=0.05), which is in contrast to results in cHL and CLL. Furthermore, Gal-1 levels did not show association with bone marrow angiogenesis, clinicopathological parameters, overall survival, or response to treatment. There was a statically significant association between Gal-1 and sCD163 levels (R=0.24, P=0.02), but not with soluble mannose receptor (P=0.92). In conclusion, our results indicate that Gal-1 is not an important serum biomarker in MM, which is in contrast to data from patients with cHL and CLL. However, the association with sCD163 is in line with previous data showing that Gal-1 may be involved in alternative (M2-like) activation of macrophages.

No abstract

Treatment of early relapses of T lymphoblastic leukemia/lymphoma is often unsuccessful. We tested an experimental regimen containing daratumumab and nelarabine in two young patients with early relapses of T lymphoblastic lymphoma and T-ALL, respectively. Both patients achieved a deep complete remission. Combining daratumumab with chemotherapy may have a role in relapsing T lymphoblastic leukemia/lymphoma.