A Promising New Therapy of Oral Ixazomib Without Rituximab for Waldenstrom Macroglobulinemia

摘要

A 73-year-old woman was admitted with complaints of low fever, fatigue, shortness of breath, and edema of the lower extremities. Hemoglobin (Hb) and platelets (PLTs) were 76-93 g/L (normal range: 110-160 g/L) and 75-103x109/L (100-300x109/L), respectively. Serum protein electrophoresis indicated that M protein and immunoglobulin M were elevated to 8.6 g/L and 11.9 g/L (0.4-2.3 g/L). Blood immunofixation electrophoresis also exhibited positive immunoglobulin M (IgM)κ. Computed tomography (CT) scans revealed multiple enlarged lymph nodes in the mediastinum, mesentery, neck, underarms, and groin with pericardial and pleural effusion and splenomegaly (Figures 1A and ​and1C).1C). A bone marrow smear revealed 7.5% lymphocytic plasma cells, whose immune phenotypes were consistent with Waldenstrom macroglobulinemia (WM). Furthermore, L265P mutation in MYD88 was detected in the bone marrow and pleural effusion. Accordingly, WM was diagnosed and the RCD regimen (rituximab, dexamethasone, cyclophosphamide) was given for 2 cycles, but her PLTs quickly decreased to 15x109/L with petechiae during the infusion of rituximab, probably due to rituximab-induced thrombocytopenia [1]. Two weeks later, PLTs gradually increased to 80x109/L, but Hb remained at 54 g/L and M protein did not decrease. A CT scan did not show any reduction of pericardial or pleural effusion. Meanwhile, a new-onset femoral neck fracture prevented her from coming to the hospital for a bortezomib-based regimen and economic status restricted her from usage of ibrutinib and ICD (ixazomib, dexamethasone, cyclophosphamide). Therefore, an oral treatment regimen was given for 1 cycle followed by 5 cycles of ID regimen (ixazomib, dexamethasone) due to neutropenia possibly induced by cyclophosphamide. Strikingly, Hb rose back to 125 g/L and PLTs remained stable at 155x109/L. M protein fell back to 0.6 g/L. A CT scan showed normal size of multiple lymph nodes and absence of pericardial and pleural effusion (Figures 1B and ​and1D).1D). The patient achieved very good partial response (VGPR) after 6 cycles of ixazomib-based regimen and remained in VGPR without maintenance for 1 year.