套细胞淋巴瘤 Mantel cell lymphoma

Ibrutinib与利妥昔单抗联合作为第一线治疗老年套细胞淋巴瘤 (12/4/2021)

Ibrutinib and rituximab combination as first-line chemotherapy-free regime for elderly mantel cell lymphoma

多数套细胞淋巴瘤（mantel cell lymphoma）患者是老年人。这项II期临床试验（NCT01880567）研究了Ibrutinib与利妥昔单抗联合初治老年患者（年龄≥65岁）的疗效和安全性。

该试验入选50例套细胞淋巴瘤患者。Ki-67％≥50％和母细胞（blastoid）形态的患者被排除。Ibrutinib与利妥昔单抗治疗长达2年，然后,Ibrutinib单独继续治疗。试验主要目的是总响应率和安全性。在可评估的样品中，进行了全外显子组从基线组织样品测序和RNA测序。患者中位年龄为71岁。 16％的患者有高风险的简化套细胞淋巴瘤的国际预后指数。有38位患者（76％）的Ki-67是低的％（<30％）,有12位患者（24％）的Ki-67中度增高（≥30％-50％）。 总响应率为96％（71％完全缓解）。在中位随访45个月后, 28位（56％）患者由于各种原因离开了试验（包括4个疾病进展，21位由于毒性和三个其它原因）。中位无进展生存期和总生存期都没有达到; 3年中位无进展生存率和总生存率分别为87％和94％。

没有患者在研究治疗中死亡。值得注意的是，11个（22％）患者有3级房颤。 3-4级的骨髓抑制患者<5％。与完全缓解者相比,在部分响应者中,CCND1，BIRC3，BANK1，SETBP1，AXIN2和IL2RA有过表达。

结论: Ibrutinib与利妥昔单抗组合是有效的老年患者套细胞淋巴瘤第一线治疗。若使用Ibrutinib,须要心血管风险基线评估。

Most mantel cell lymphoma (MCL) patients are elderly. The phase II clinical trial (NCT01880567) studied the efficacy and safety of Ibrutinib and rituximab combination as first-line therapy for older patients (age ≥ 65 years).

The trial enrolled 50 cases of MCL patients. Patients with Ki-67% ≥ 50% and blastoid cell morphology were excluded. Ibrutinib and rituximab administration were up to 2 years, with continuation of Ibrutinib alone. The primary objective of the trial was overall response rate and safety. In evaluable samples, whole-exome were performed from baseline tissue samples. The median age was 71 years. Sixteen percent of patients had high-risk simplified international MCL prognostic index. The Ki-67% was low (<30%) in 38 patients (76%), and moderately high (> 30%-50%) in 12 patients (24%).

The best overall response rate was 96% (71% complete remission). After a median follow-up of 45 months, 28 (56%) patients came off the trial due to various reasons, including 4 disease progression, 21 toxicity and three other reasons. There is no progressive life and total survival period; 3 years no progressive survival rate and total survival rate are 87% and 94%, respectively.

No patient died on study drugs. Of note, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression occurred in <5% of patients. Compared with those the complete response, differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2 and IL2RA was noted in partial responders.

Conclusion: Ibrutinib and rituximab combination is effective as a first line treatment for older patients with MCL. If Ibrutinib is used in the future, a cardiovascular risk baseline is required.