Silkenstedt E, Dreyling M
Department of Medicine III, LMU Hospital, Munich, Germany.
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):42-47. doi: 10.1182/hematology.2024000546.
An Ara-C-containing intensified induction therapy followed by autologous stem cell transplantation (ASCT) is considered a highly effective treatment strategy in younger mantle cell lymphoma (MCL) patients, inducing long-lasting remissions. However, ASCT is also hampered by acute and delayed toxicity. Thus, alternative first-line treatment strategies without ASCT but including novel agents are under investigation. With the recently published results of the TRIANGLE trial, showing superiority of an ibrutinib-containing immunochemotherapy induction followed by ASCT compared with the standard therapy and, more strikingly, a noninferiority of an ibrutinib-containing regimen without ASCT compared with the standard regimen with ASCT, we consider the addition of ibrutinib to first-line therapy in younger MCL patients as a new standard of care. Whether ASCT, with additional toxicity, still adds benefit to ibrutinib-based treatment in subsets of patients is not yet determined. In addition, it remains unclear how effective Bruton's tyrosine kinase inhibitor (BTKi) therapy will be in the relapsed setting for patients who received BTKi as part of first-line therapy. It also remains unclear whether the TRIANGLE data can be extrapolated to other BTKi, which is particularly relevant considering it is no longer FDA approved for MCL. Until then, individual patient characteristics and preferences, disease biology, and estimation of risk of toxicity needs to be taken into account when deciding about the addition of ASCT to an ibrutinib-containing induction therapy. For patients with TP53 aberrations, ASCT should not be recommended due to potential toxicity and limited efficacy in this high-risk subgroup. Large randomized clinical trials such as ECOG-ACRIN 4151 will help to ultimately clarify the role of ASCT.
含阿糖胞苷的强化诱导治疗后进行自体干细胞移植(ASCT)被认为是年轻套细胞淋巴瘤(MCL)患者的一种高效治疗策略,可诱导持久缓解。然而,ASCT也受到急性和延迟毒性的阻碍。因此,正在研究不进行ASCT但包括新型药物的替代一线治疗策略。随着TRIANGLE试验最近公布的结果,显示含伊布替尼的免疫化疗诱导后进行ASCT优于标准疗法,更显著的是,不含ASCT的含伊布替尼方案与含ASCT的标准方案相比不劣效,我们认为在年轻MCL患者的一线治疗中添加伊布替尼是一种新的护理标准。ASCT伴有额外毒性,对于某些患者亚组,它是否仍能为基于伊布替尼的治疗增加益处尚未确定。此外,对于接受BTKi作为一线治疗一部分的患者,布鲁顿酪氨酸激酶抑制剂(BTKi)疗法在复发情况下的效果仍不清楚。TRIANGLE数据是否可以外推到其他BTKi也不清楚,考虑到它不再被FDA批准用于MCL,这一点尤其相关。在此之前,在决定是否在含伊布替尼的诱导治疗中添加ASCT时,需要考虑个体患者特征和偏好、疾病生物学以及毒性风险评估。对于有TP53异常的患者,由于该高危亚组存在潜在毒性且疗效有限,不应推荐ASCT。诸如ECOG-ACRIN 4151这样的大型随机临床试验将有助于最终阐明ASCT的作用。