Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial.
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial.
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DOI：
10.1200/jco.21.02321
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发表时间：
2022-04-10
期刊：
影响因子：
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通讯作者：
López-Guillermo A
中科院分区：
文献类型：
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作者：
Giné E;de la Cruz F;Jiménez Ubieto A;López Jimenez J;Martín García-Sancho A;Terol MJ;González Barca E;Casanova M;de la Fuente A;Marín-Niebla A;Muntañola A;González-López TJ;Aymerich M;Setoain X;Cortés-Romera M;Rotger A;Rodríguez S;Medina Herrera A;García Sanz R;Nadeu F;Beà S;Campo E;López-Guillermo A
对套细胞淋巴瘤（MCL）的惰性临床形式的个体化管理的需要越来越被认识到。我们假设，伊鲁替尼联合利妥昔单抗（IR）的定制治疗可以在这些患者中获得显着的反应。这是一项在12家西班牙GELTAMO研究中心进行的多中心、单组、开放标签、II期研究，采用两阶段设计（ClinicalTrials.gov标识符：NCT 02682641）。符合以下标准的惰性临床形式的既往未接受过治疗的MCL患者符合资格：无疾病相关症状，非胚样变异，Ki-67 <30%，最大肿瘤直径≤ 3 cm。招募了白血病非淋巴结和淋巴结亚型。患者接受了伊鲁替尼560 mg每日一次和共8剂利妥昔单抗375 mg/m2。如果持续检测不到微小残留病（MRD），2年后可停用伊曲替尼。主要终点是根据Lugano标准在12个周期后达到的完全缓解（CR）率。入组了50例MCL患者（男性66%;中位年龄65岁）。12个周期治疗后，42例（84%; 95% CI，74 - 94）患者总体缓解，包括40例（80%; 95% CI，69 - 91）CR。此外，87%（95%CI，77 - 97）的病例在外周血中达到了不可检测的MRD。2年时，35例可评价患者中有24例（69%）可因无法检测到MRD而停用伊鲁替尼。4例患者发生疾病进展; 3例为非淋巴结MCL，在入组时携带高基因组复杂性和TP 53突变。除1例重度再生障碍性贫血患者外，未观察到意外毒性。一线IR联合治疗在惰性临床形式的MCL中实现了高CR率和不可检测的MRD。除了TP 53突变的病例外，在MRD检测不到的病例中停药似乎是合适的。
The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients. This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 12 Spanish GELTAMO sites (ClinicalTrials.gov identifier: NCT02682641). Previously untreated MCL patients with indolent clinical forms defined by the following criteria were eligible: no disease-related symptoms, nonblastoid variants, Ki-67 < 30%, and largest tumor diameter ≤ 3 cm. Both leukemic non-nodal and nodal subtypes were recruited. Patients received ibrutinib 560 mg once daily and a total of eight doses of rituximab 375 mg/m2. Ibrutinib could be discontinued after 2 years in the case of sustained undetectable minimal residual disease (MRD). The primary end point was the complete response (CR) rate achieved after 12 cycles according to Lugano criteria. Fifty patients with MCL (male 66%; median age 65 years) were enrolled. After 12 cycles of treatment, 42 (84%; 95% CI, 74 to 94) patients had an overall response, including 40 (80%; 95% CI, 69 to 91) with CR. Moreover, undetectable MRD in peripheral blood was achieved in 87% (95% CI, 77 to 97) of cases. At 2 years, 24 of 35 evaluable patients (69%) could discontinue ibrutinib because of undetectable MRD. Four patients had disease progression; three were non-nodal MCL and carried high genomic complexity and TP53 mutations at enrollment. No unexpected toxicity was seen except one patient with severe aplastic anemia. Frontline IR combination achieves a high rate of CRs and undetectable MRD in indolent clinical forms of MCL. Discontinuation seems appropriate in cases with undetectable MRD, except for TP53-mutated cases.