Adam Z, Krejčí M, Pour L, Weinbergerová B, Sandecká V, Štork M, Boichuk I, Řehák Z, Keřkovský M, Koukalová R, Zdražilová-Dubská L, Čechová B, Král Z
Klin Onkol. 2024;37(6):451-462. doi: 10.48095/ccko2024451.
Waldenström's macroglobulinemia (WM) is a very rare disease with an incidence 10times lower than that of multiple myeloma. The incidence of WM is also significantly lower than that of the other CD20+ low-grade lymphomas. The rarity of WM is the reason why registration studies of new drugs used for multiple myeloma or the more common CD20+low-grade lymphomas do not cover WM. Data on the efficacy of proteasome inhibitors in WM can be drawn from case descriptions, small series of patients and a few phase II clinical trials. The aim of this case report and review is to inform about our experience with the treatment of WM with bortezomib and then ixazomib and to present an overview of publications on proteasome inhibitors in WM.
We describe a patient who, after 8 years of asymptomatic course of WM, had the first fulminant progression with severe pancytopenia at the age of 74 years. For the first-line treatment, he was treated with dexamethasone and rituximab, and after alleviation of pancytopenia, with bendamustine. Monoclonal immunoglobulin IgM (M-IgM) dropped from 40 g/L to the level as low as 6.9 g/L, which meant partial remission (PR) accompanied with normal blood count values. After 29 months of PR, the patient experienced a fulminant relapse of WM, accompanied by severe pancytopenia. Rituximab and dexamethasone were the backbone of treatment with addition of bortezomib for its significantly lower myelosuppression compared to alkylating agents. Treatment with the triple combination of bortezomib, rituximab, and dexamethasone was effective, however, after five cycles, bortezomib had to be discontinued for severe neurotoxicity. The sixth cycle contained rituximab and dexamethasone, and from the seventh cycle, ixazomib was started. The patient underwent seven cycles (months) of treatment consisting of ixazomib, rituximab and dexamethasone (14 cycles of treatment in total).
M-IgM decreased from 30 g/L at the beginning of the treatment to 4.0 g/L at the end of treatment and further decreased to a value of 2.8 g/L at the eighth month after the end of the treatment. A deeper decrease in M-IgM than after first-line treatment was achieved and the patient now meets the criteria for a very good partial remission.
According to the described experience and according to the review of publications evaluating proteasome inhibitors in WM, the combination of ixazomib with rituximab and dexamethasone excels with very good tolerance and high efficacy, approaching the efficacy of the combination of rituximab with bendamustine. This combination has its place particularly in patients with WM and cytopenia.
华氏巨球蛋白血症（WM）是一种非常罕见的疾病，其发病率比多发性骨髓瘤低10倍。WM的发病率也显著低于其他CD20+低级别淋巴瘤。WM的罕见性导致用于多发性骨髓瘤或更常见的CD20+低级别淋巴瘤的新药注册研究未涵盖WM。蛋白酶体抑制剂在WM中的疗效数据可从病例描述、小系列患者及少数II期临床试验中获取。本病例报告及综述的目的是介绍我们使用硼替佐米然后伊沙佐米治疗WM的经验，并概述关于蛋白酶体抑制剂治疗WM的出版物。
我们描述了一名患者，其WM无症状病程8年后，在74岁时首次出现暴发性进展并伴有严重全血细胞减少。一线治疗时，他接受了地塞米松和利妥昔单抗治疗，全血细胞减少缓解后，接受了苯达莫司汀治疗。单克隆免疫球蛋白IgM（M-IgM）从40 g/L降至低至6.9 g/L的水平，这意味着部分缓解（PR）且血细胞计数正常。PR持续29个月后，患者经历了WM的暴发性复发，伴有严重全血细胞减少。利妥昔单抗和地塞米松是治疗的基础，加用硼替佐米是因为其骨髓抑制作用明显低于烷化剂。硼替佐米、利妥昔单抗和地塞米松三联组合治疗有效，然而，五个周期后，硼替佐米因严重神经毒性不得不停药。第六个周期包含利妥昔单抗和地塞米松，从第七个周期开始使用伊沙佐米。患者接受了七个周期（月）由伊沙佐米、利妥昔单抗和地塞米松组成的治疗（共14个治疗周期）。
M-IgM从治疗开始时的30 g/L降至治疗结束时的4.0 g/L，并在治疗结束后第八个月进一步降至2.8 g/L。M-IgM的下降程度比一线治疗后更深，患者现在符合非常好的部分缓解标准。
根据所述经验以及对评估蛋白酶体抑制剂治疗WM的出版物的综述，伊沙佐米与利妥昔单抗和地塞米松的联合使用耐受性良好且疗效高，接近利妥昔单抗与苯达莫司汀联合使用的疗效。这种联合尤其适用于患有WM和血细胞减少症的患者。
