Treon S P, Branagan A R, Hunter Z, Santos D, Tournhilac O, Anderson K C
Waldenstrom's Macroglobulinemia Program, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02116, USA.
Ann Oncol. 2004 Oct;15(10):1481-3. doi: 10.1093/annonc/mdh403.
The anti-CD20 monoclonal antibody rituximab is an important therapeutic in Waldenstrom's macroglobulinemia (WM), producing response rates of 50-70%. Responses, which are based on serum IgM levels, have typically been evaluated at 12 weeks. Paradoxically, we have observed that serum IgM levels can abruptly rise following rituximab therapy in patients with WM, and can often lead to morbidity on the basis of hyperviscosity.
Eleven WM patients with CD20+ tumor cells who received rituximab at our Institution and had serum IgM levels measured within a 12-week period following start of therapy were evaluated. Therapy consisted of four weekly infusions of rituximab at 375 mg/m(2). Pre- and post-therapy serum IgM levels were determined by nephelometry and corresponding serum viscosity levels were determined by viscometry.
Ten of the 11 patients demonstrated an abrupt rise in serum IgM levels, with a >25% increase occurring in eight (73%) patients. Mean serum IgM levels for all 10 spiking patients rose from 4370 (range, 655-7940) to a peak of 5865 (range, 872-11 800) mg/dl (P=0.004), which occurred at a mean of 4 (range, 1-8) weeks following initiation of therapy. Mean serum viscosity levels also increased from 3.5 to 5.6 centipoise (CP) (P=0.09) in eight patients for whom pre- and post-therapy studies were obtained. A subdural hemorrhage occurred in one patient when serum IgM levels rose from 7530 to 11 800 mg/dl, and serum viscosity increased from 3.9 to 10.1 CP. Two other spiking patients with pre-therapy IgM levels of >5000 mg/dl experienced worsening headaches and/or epistaxis attributed to increasing serum viscosity.
Abrupt increases in serum IgM levels commonly occur following rituximab therapy in WM. Careful clinical and laboratory monitoring is warranted, particularly if patients have pre-therapy serum IgM levels of >5000 mg/dl. The mechanism of this effect is under active investigation, and may be related to CD20 signaling triggered by rituximab.
抗CD20单克隆抗体利妥昔单抗是治疗华氏巨球蛋白血症（WM）的重要药物，有效率为50%-70%。通常根据血清IgM水平评估疗效，评估时间点为12周。矛盾的是，我们观察到WM患者在接受利妥昔单抗治疗后血清IgM水平会突然升高，且常因血液黏稠度增加而导致发病。
对11例携带CD20+肿瘤细胞的WM患者进行评估，这些患者在我们机构接受了利妥昔单抗治疗，并在治疗开始后的12周内测量了血清IgM水平。治疗方案为每周静脉输注利妥昔单抗4次，剂量为375mg/m²。治疗前后的血清IgM水平通过散射比浊法测定，相应的血清黏度水平通过黏度测定法测定。
11例患者中有10例血清IgM水平突然升高，其中8例（73%）升高超过25%。所有10例血清IgM水平升高的患者，其平均血清IgM水平从4370（范围655-7940）mg/dl升至峰值5865（范围872-11800）mg/dl（P=0.004），出现在治疗开始后的平均4（范围1-8）周。在8例有治疗前后研究数据的患者中，平均血清黏度水平也从3.5厘泊（CP）升至5.6厘泊（P=0.09）。1例患者血清IgM水平从7530mg/dl升至11800mg/dl，血清黏度从3.9CP升至10.1CP时发生了硬膜下出血。另外2例治疗前IgM水平>5000mg/dl且血清IgM水平升高的患者，因血清黏度增加出现了头痛加重和/或鼻出血。
WM患者接受利妥昔单抗治疗后，血清IgM水平通常会突然升高。需要进行仔细的临床和实验室监测，特别是对于治疗前血清IgM水平>5000mg/dl的患者。这种效应的机制正在积极研究中，可能与利妥昔单抗触发的CD20信号传导有关。
