ZR2方案治疗老年难治性弥漫大B细胞淋巴瘤疗效观察

Efficacy of ZR2 regimen in the treatment of refractory diffuse large B-cell lymphoma in the elderly

目的:观察泽布替尼联合来那度胺及利妥昔单抗(ZR2方案)治疗老年难治性弥漫大B细胞淋巴瘤(DLBCL)的近期疗效及不良反应。方法:采用ZR2方案(泽布替尼320mg/d,口服,第1~21天;来那度胺25mg/d,口服,第1~14天;利妥昔单抗375mg/m^(2),静脉滴注,第0天)治疗20例年龄>65岁的难治性DLBCL患者,21d为1个疗程,持续6~8个周期,达完全缓解后给予来那度胺单药维持治疗。结果:20例患者共完成90个疗程,中位疗程数5(2~8)个,总有效率为75.0%(15/20),其中完全缓解率为65.0%(13/20),≥80岁患者的完全缓解率为75.0%(6/8)。乳酸脱氢酶≥245U/L与<245U/L、双表达(DEL、c-Myc≥40%伴Bcl-250%)与无双表达(non-DEL)患者的完全缓解率比较,差异均无统计学意义(P>0.05)。中位随访5.5(3~8)个月,总生存率为90.0%,中位无进展生存期及中位总生存期均未达到。不良反应主要为血液系统不良反应,大多在Ⅱ级及以下水平,经治疗后好转;治疗及随访期间未出现严重的心脏(如心律失常、心房颤动、心力衰竭)毒性及肾脏功能异常等不良反应。结论:ZR2方案治疗老年难治性DLBCL安全、耐受且具有一定疗效,可作为临床合适的治疗选择。

Objective: To observe the short-time effects and adverse events of zanubrutinib combined with lenalidomide and rituximab(ZR2) for elderly patients with refractory diffuse large B-cell lymphoma(DLBCL). Methods: A total of 20 patients(more than 65 years old) with refractory DLBCL who had received R-miniCHOP for at least 2 cycles but did not achieve complete remission or developed rapidly after a brief complete remission were treated with ZR2(zanubrutinib 320 mg/d, oral, day 1-21;lenalidomide 25 mg/d, oral, day 1-14;rituximab 375 mg/m~2, iv drip, day 0). 21 days was a course of treatment, lasting for 6-8 cycles. After achieving complete remission, patients were given lenalidomide single drug for maintenance treatment. Results: The 20 patients completed total of 90 cycles, at the 5 median courses, the overall response rate at the end of induction phase was 75.0%(15/20), 13 patients(65.0%) achieved complete response. The complete response rate was 75.0%(6/8) in patients older than 80 years. There was no significant difference in the complete remission rate between patients with lactate dehydrogenase≥245 U/L and <245 U/L, double expression(DEL, c-Myc≥40% and Bcl-2≥50%) and non-double expression(non-Del)(P>0.05). The median follow-up was 5.5(3-8) months. The overall survival rate was 90.0%. The median progression free survival and median overall survival were not achieved. The main adverse events were hematological adverse events, which were mostly in gradeⅡand below, and improved after treatment. There were no serious adverse events such as cardiac toxicity(arrhythmia, atrial fibrillation, heart failure), abnormal renal function during treatment and follow-up. Conclusion: ZR2 regimen is safe, tolerable and effective in the treatment of senile refractory DLBCL, which can be used a suitable choice for clinical treatment.