小柯机器人

美国德克萨斯大学安德森癌症中心Michael L. Wang团队研究了伊鲁替尼联合苯达莫司汀和利妥昔单抗治疗初治套细胞淋巴瘤的疗效。该项研究成果发表在2022年6月3日出版的《新英格兰医学杂志》上。

伊鲁替尼是一种布鲁顿酪氨酸激酶抑制剂，当与苯达莫司汀和利妥昔单抗联合使用治疗初治的套细胞淋巴瘤老年患者，之后再进行利妥昔单抗维持治疗时，可能具有临床益处。

研究组随机分配65岁及以上的患者接受伊鲁替尼（560 mg，每日口服一次，直至疾病进展或出现不可接受的毒性反应）或安慰剂治疗，加上6个周期的苯达莫司汀（90 mg/m²体表面积）和利妥昔单抗（375 mg/m²）。有客观缓解（完全或部分缓解）的患者接受利妥昔单抗维持治疗，每8周一次，最多增加12剂。主要终点是研究者评估的无进展生存。还评估了总体生存和安全性。

523名患者随机分组后，261名接受伊鲁替尼治疗，262名接受安慰剂治疗。在84.7个月的中位随访中，伊鲁替尼组的中位无进展生存期为80.6个月，显著长于安慰剂组的52.9个月，疾病进展或死亡的危险比为0.75。伊鲁替尼组完全缓解的患者百分比为65.5%，安慰剂组为57.6%，差异不显著。两组的总生存率相似。伊鲁替尼组治疗期间3级或4级不良事件的发生率为81.5%，安慰剂组为77.3%。

研究结果表明，伊鲁替尼联合标准化学免疫治疗可显著延长无进展生存期。联合治疗的安全性与已知个别药物的安全性一致。

附：英文原文

Title: Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma | NEJM

Author: Michael L. Wang, M.D.,, Wojciech Jurczak, M.D., Ph.D.,, Mats Jerkeman, M.D., Ph.D.,, Judith Trotman, F.R.A.C.P.,, Pier L. Zinzani, M.D., Ph.D.,, David Belada, M.D., Ph.D.,, Carola Boccomini, M.D.,, Ian W. Flinn, M.D., Ph.D.,, Pratyush Giri, F.R.A.C.P.,, Andre Goy, M.D.,, Paul A. Hamlin, M.D.,, Olivier Hermine, M.D., Ph.D.,, José-ángel Hernández-Rivas, M.D., Ph.D.,, Xiaonan Hong, M.D.,, Seok Jin Kim, M.D., Ph.D.,, David Lewis, F.R.C.Path., Ph.D.,, Yuko Mishima, M.D., Ph.D.,, Muhit zcan, M.D.,, Guilherme F. Perini, M.D.,, Christopher Pocock, M.D., Ph.D.,, Yuqin Song, M.D., Ph.D.,, Stephen E. Spurgeon, M.D.,, John M. Storring, M.D.,, Jan Walewski, M.D.,, Jun Zhu, M.D., Ph.D.,, Rui Qin, Ph.D.,, Todd Henninger, Ph.D.,, Sanjay Deshpande, M.D.,, Angela Howes, Ph.D.,, Steven Le Gouill, M.D., Ph.D.,, and Martin Dreyling, M.D.

Issue&Volume: 2022-06-03

Abstract:

Background

Ibrutinib, a Bruton’s tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma.

Methods

We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed.

Results

Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P=0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group.

Conclusions

Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs.

DOI: 10.1056/NEJMoa2201817

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2201817

The New England Journal of Medicine：《新英格兰医学杂志》，创刊于1812年。隶属于美国麻省医学协会，最新IF：176.079
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