Comparative Outcomes of Immunochemotherapy with RCD (rituximab, cyclophosphamide, dexamethasone) and BCD (bortezomib, cyclophosphamide, dexamethasone) in Waldenstrom Macroglobulinaemia: NCT02971982

Objective: To compare the outcomes of immunochemotherapy with rituximab based treatment and bortezomib treatment in pantines with Waldenstrom macroglobulinaemia

Method: The randomized study enrolling 11eligible patients at first affiliated hospital of Soochow university aged from 44 years old to 71 years old. All of them were diagnosed by bone marrow biopsy, immunofixed electroresis with IgM-M protein and MYD88L265P mutation, all of them had clinical symptoms such as fever, weak, loss of weigh, hemorrhage and so on. These patients with newly diagnosed WM were randomly to two groups to receive treatment. 4 patients were treated by bortezomib, cyclophosphamide and dexamethasone (PCD), the other 7 patients were treated by rituximab, cyclophosphamide and dexamethasone (RCD), the primary end point was overall response rate (ORR), and major response rate (MRR).

Results: The median age of 11 patients was 63 years old (range: 44-71 years), with a male to female ratio was 4.5. ALL of them had clinical symptoms, most of them had non-specific symptoms such as weak, fever (36.6%, 4/11), and loss of weight (18.2%, 2/11).One of them had coagulation disorder with retroperitoneal hematoma, and one had rashes. 4 patients treated by PCD received 6 cycles and 7 patients treated by RCD received 3 to 6 cycles (average 5 cycles). The response evaluation is arcaded by the symptoms and M-protein in plasma. All of the clinical symptoms were remitted by treatment in each group after one to four cycles. 9 patients with anemia at first and 88.8% (8/9) were remitted. To evaluate the M-protein, the overall response rate (ORR) of Patients who received PCD treatment is 75% (3/4), and major reaction rate (MRR) (1 patient was PR, 1 patient was VGPR, and 1 patient was CR) is 75%. The ORR of patents received RCD treatment is 42.85% (3/7), and the MRR is 14.28(1 patient reached PR). The two group is not statistical significance in ORR (P=0.554), but the MRR is significantly better in the PCD arm compared with RCD arm (95%CI, 75% to 42.85%, P=0.044).The toxicity of the PCD arm was peripheral neuritis (100%), I to II grade, mostly accrued after 4 cycles of bortezomib, and one of them with dosage reduction to 1.0mg/m2 by bortezomib. The severe adverse event was hepatotoxicity by extending interval treatment of each cycle. The major toxicity of RCD arm was infusion reaction of rituximab (37.1%, 4/7), such as fever, chest congestion and hypoxemia, mostly at first to third cycle. All can be relieved by slow infusion and oxygen inhalation. The incidence rate of toxicity was similar in two groups (P=0.125).

Conclusion: Rituximab and Bortezomib are new immunochemotherapy for Waldenstrom macroglobulinaemia, both (combination with other agent) are recommended as a first-line treatment for WM. In our preliminary statistics, both of them had effect, but the MRR is better in PCD group. Bortezomib may can act on the NF-κB cytokine pathway. But our samples were limited, we still need to be confirmed by expanding the samples quantity and extending the time of intervention.