Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. Issue 11 (10th April 2022)

• Record Type: Journal Article
• Authors: Giné, Eva; de la Cruz, Fátima; Jiménez Ubieto, Ana; López Jimenez, Javier; Martín García-Sancho, Alejandro; Terol, M. José; González Barca, Eva; Casanova, María; de la Fuente, Adolfo; Marín-Niebla, Ana; Muntañola, Ana; González-López, Tomás José; Aymerich, Marta; Setoain, Xavier; Cortés-Romera, Montserrat; Rotger, Amanda; Rodríguez, Sonia; Medina Herrera, Alejandro; García Sanz, Ramón; Nadeu, Ferran; Beà, Silvia; Campo, Elías; López-Guillermo, Armando
• Is Part Of: Journal of clinical oncology. Volume 40:Issue 11(2022)
• Page Start: 1196
• Page End: 1205
• Publication Date: 2022-04-10
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.02321
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: 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. METHODS: 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/m 2 . 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. RESULTS: 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. CONCLUSION: 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. Abstract :