Cytomegalovirus infection during daratumumab therapy in patients with newly diagnosed multiple myeloma.

The introduction of daratumumab has improved treatment outcomes for multiple myeloma (MM). However, infectious complications are a concern in patients receiving daratumumab. Although some reports have explored the association between daratumumab and cytomegalovirus (CMV) infection, most of these have focused on relapsed or refractory cases, and few describe patients with newly diagnosed MM (NDMM). In this study, we retrospectively analyzed CMV infections in 53 patients with NDMM who received daratumumab as induction therapy. CMV infection was defined as CMV antigenemia positivity. The median age at treatment initiation was 71 years (range, 50-82 years), and 50.9% of the patients were female. The median duration of daratumumab administration was 10.0 months (range, 0.3-63.8 months). Nine patients developed CMV infection, and the cumulative incidence rate at six months was 18.1% (95% confidence interval: 8.9-30.1%). One patient experienced CMV retinitis and required antiviral therapy, while the remaining eight patients did not require treatment and could be managed through observation. Few cases of CMV infection during daratumumab treatment for NDMM required treatment. However, the incidence of CMV infection was not negligible, suggesting that regular monitoring for CMV is worth considering to ensure more appropriate management during daratumumab treatment.

Cytomegalovirus Reactivation During Elotuzumab Therapy in Patients with Multiple Myeloma.

INTRODUCTION: Some treatments are associated with cytomegalovirus (CMV) reactivation (CMVRA) in patients with multiple myeloma (MM). However, no reports exist on the association between elotuzumab and CMVRA. Therefore, we assessed the incidence of CMVRA in patients with MM who received elotuzumab therapy. METHODS: The medical records of 85 patients who underwent elotuzumab therapy were included in the retrospective analysis for CMV positivity. RESULTS: Thirty patients were tested for CMV antigenemia during elotuzumab therapy, and 16 were positive for CMV antigenemia; the cumulative incidence rate of CMVRA six months after elotuzumab initiation was 18.4%. A history of allogeneic stem cell transplantation (allo-HSCT) was significantly more common in the CMVRA group (31.2%) than that of the group without CMVRA (8.7%). However, even among patients who did not undergo allo-HSCT, the cumulative incidence rate of CMVRA at six months was 15.1%. During CMVRA, the symptoms included fever in seven cases, while retinitis and septic shock were observed in one case each. Five patients required antiviral therapy and CMV antigenemia resolved in all but one case. CONCLUSION: Although the patient population was heterogeneous, CMVRA cannot be underestimated during elotuzumab therapy, and evaluation of CMVRA, especially in symptomatic cases, is clinically important.

Real-world clinical outcomes in patients with relapsed and refractory multiple myeloma receiving VTD-PACE treatment in the era of monoclonal antibodies.

Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1 months, during which they received a median of two cycles of VTD-PACE. The overall response rate (ORR) was 66.7%; ORRs of 53.1 and 82.1% were noted in patients with ≥ 4 and ≤ 3 prior lines (P = 0.027), respectively. The median overall survival (OS) was 17 months, with a median progression-free survival (PFS) of 9.8 months. Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and OS of patients who received or did not receive HSCT or CART after VTD-PACE treatment. Patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE showed a trend of longer PFS and OS than those who did not undergo subsequent HSCT or CART. The median OS in patients with and without renal dysfunction was 10.7 months and 21.5 months, respectively (P = 0.0091). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response can be expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use.

[Venetoclax and azacitidine induced cytogenetic response in an elderly patient with IDH2- and DNMT3A-mutated refractory acute myeloid leukemia].

The optimal regimen for refractory acute myeloid leukemia (AML) in the elderly with good performance status has not been established. A 71-year-old man was admitted to our hospital with pancytopenia and 1.0% blasts in the peripheral blood. The patient was diagnosed with AML with DNMT3A (R882H)- and IDH2 (R172K)-positive myeloblasts. He received a reduced dose of idarubicin and cytarabine therapy. However, induction failure with 20% bone marrow blasts and DNMT3A mutations were observed. A reinduction therapy with venetoclax and azacitidine (VEN+AZA) was administered and led to a sustained complete response with significantly reduced DNMT3A-mutated blasts. Even 9 months after starting VEN+AZA, the patient is still alive and healthy without AML recurrence. Thus, VEN+AZA therapy may be highly effective for treating IDH2- and DNMT3A-mutated AML in elderly patients.