TY - JOUR
T1 - Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma
AU - Jain, Preetesh
AU - Zhao, Shuangtao
AU - Lee, Hun Ju
AU - Hill, Holly A.
AU - Ok, Chi Young
AU - Kanagal-Shamanna, Rashmi
AU - Hagemeister, Fredrick B.
AU - Fowler, Nathan
AU - Fayad, Luis
AU - Yao, Yixin
AU - Liu, Yang
AU - Moghrabi, Omar B.
AU - Navsaria, Lucy
AU - Feng, Lei
AU - Nogueras Gonzalez, Graciela M.
AU - Xu, Guofan
AU - Thirumurthi, Selvi
AU - Santos, David
AU - Iliescu, Cezar
AU - Tang, Guilin
AU - Medeiros, L. Jeffrey
AU - Vega, Francisco
AU - Avellaneda, Michelle
AU - Badillo, Maria
AU - Flowers, Christopher R.
AU - Wang, Linghua
AU - Wang, Michael L.
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2022/1/10
Y1 - 2022/1/10
N2 - PURPOSE Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years). METHODS We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial (NCT01880567). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed. RESULTS The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was noted in partial responders compared with patients with complete response. CONCLUSION IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.
AB - PURPOSE Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years). METHODS We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial (NCT01880567). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed. RESULTS The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was noted in partial responders compared with patients with complete response. CONCLUSION IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.
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U2 - 10.1200/JCO.21.01797
DO - 10.1200/JCO.21.01797
M3 - Article
C2 - 34797699
AN - SCOPUS:85123388222
SN - 0732-183X
VL - 40
SP - 202
EP - 212
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -