International journal of hematology
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Chimeric antigen receptor (CAR) T cell therapy, an immunotherapy using gene-modified T cells, has recently made a big success. CAR T cells targeting CD19 is highly effective against B cell malignancies. ⋯ We are also developing CAR T cells targeting a protein conformation that is preferentially detected in myeloma cells. In this review, I will summarize the state of art in the field of CAR T cell therapy against myeloma, and also present our effort to develop a new CAR T cell therapy.
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Multicenter Study
Bortezomib, lenalidomide, and dexamethasone in transplant-eligible newly diagnosed multiple myeloma patients: a multicenter retrospective comparative analysis.
The combination of bortezomib, lenalidomide, and dexamethasone (VRD) is used as induction treatment in multiple myeloma; however, the optimum schedule for this regimen remains controversial. In this retrospective study, we compared the efficacy and tolerability of twice-weekly VRD (twVRD) and modified VRD-lite in transplant-eligible myeloma patients. Fifty-five patients (median age 61 years) were included; 22 received twVRD (bortezomib [1.3 mg/m2 on days 1, 4, 8, and 11] and lenalidomide [25 mg/body on days 1-14] over 21-day cycles) and 33 received modified VRD-lite (bortezomib [1.3 mg/m2 on days 1, 8, 15, and 22) and lenalidomide [15 mg/body on days 2-7, 9-14, 16-21] over 28-day cycles). ⋯ The response rate and PFS were similar between the groups, regardless of cytogenetic risk and age. The incidence of peripheral neuropathy ≥ grade 2 and thrombocytopenia ≥ grade 3 was higher in the twVRD group (27.2% vs. 0.0%, P = 0.003 and 27.2% vs. 0.0%, P = 0.003). In conclusion, modified VRD-lite had similar efficacy with, but better tolerability than, twVRD in transplant-eligible patients.
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How low-dose anti-thymocyte globulin (ATG) for prophylaxis of graft-versus-host disease (GVHD) influences immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HCT) remains incompletely understood. We prospectively enrolled 41 consecutive adult patients and conducted cytometry-based immunophenotyping for 12 months after allo-HCT. Rabbit ATG (Thymoglobulin) was administered at a median total dose of 1.75 mg/kg in 16 of the 41 patients. ⋯ No significant difference was observed between the two groups in the reconstitution of other T cells (effector, memory, Th1, Th2, Th17, Treg, and Tfh), B cells (transitional, naïve, memory, and plasmablast), NK cells (regulatory and cytolytic), or dendritic cells (myeloid and plasmacytoid). Patients with fewer CD4+ naïve T cells than the median count (7.60 cells/µL) at two months after allo-HCT developed chronic GVHD less frequently than those with CD4+ naïve T cells above the median count (2-year cumulative incidences were 0.31 and 0.53, respectively; p = 0.133). This pilot study suggests low-dose Thymoglobulin suppresses the recovery of naïve T cells after allo-HCT, which may contribute to a lower incidence of chronic GVHD.
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Allogeneic hematopoietic cell transplantation (allo-HSCT) is considered the curative treatment option in patients with aggressive adult T cell leukemia/lymphoma (ATLL), but the treatment of relapse after allo-HSCT remains a major challenge. We report a case of ATLL that was treated with sequential mogamulizumab (MOG) and lenalidomide (LEN) for early relapse after allo-HSCT. A 73-year-old Japanese male with acute-type ATLL underwent haploidentical-HSCT with post-transplant cyclophosphamide. ⋯ Although graft-versus-host disease exacerbated and progressed to TEN, a complete response was achieved after successful treatment of TEN. These agents may thus enhance anti-ATLL activity by immune modulation. Further investigation is necessary to determine the optimal use of MOG and LEN in relapsed ATLL after allo-HSCT.
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Multicenter Study Clinical Trial
Safety and efficacy of intravenous ferric carboxymaltose in Japanese patients with iron-deficiency anemia caused by digestive diseases: an open-label, single-arm study.
Iron-deficiency anemia (IDA) accounts for majority of anemia. Although iron replacement therapy is effective, in Japan, conventional iron formulations have disadvantages such as gastrointestinal side effects for oral formulations and issues of frequent administration for intravenous (IV) formulations. Ferric carboxymaltose (FCM), which overcomes these limitations, is widely used as an IV iron source overseas. ⋯ All events were as expected from the safety profile of IV iron. The mean change from baseline (10.39 g/dL) to the highest observed hemoglobin level was 3.31 g/dL. These results indicate the safety and efficacy of FCM for treating IDA caused by digestive diseases in Japanese patients.