TY - JOUR
T1 - Smart Start
T2 - Rituximab, Lenalidomide, and Ibrutinib in Patients With Newly Diagnosed Large B-Cell Lymphoma
AU - Westin, Jason
AU - Davis, R. Eric
AU - Feng, Lei
AU - Hagemeister, Fredrick
AU - Steiner, Raphael
AU - Lee, Hun Ju
AU - Fayad, Luis
AU - Nastoupil, Loretta
AU - Ahmed, Sairah
AU - Rodriguez, Alma
AU - Fanale, Michelle
AU - Samaniego, Felipe
AU - Iyer, Swaminathan P.
AU - Nair, Ranjit
AU - Oki, Yasuhiro
AU - Fowler, Nathan
AU - Wang, Michael
AU - Ma, Man Chun John
AU - Vega, Francisco
AU - McDonnell, Timothy
AU - Pinnix, Chelsea
AU - Griffith, Donna
AU - Lu, Yang
AU - Tewari, Sanjit
AU - Sun, Ryan
AU - Scott, David W.
AU - Flowers, Christopher R.
AU - Neelapu, Sattva
AU - Green, Michael R.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - PURPOSEChemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.METHODSWe enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m2 intravenous once on day 1, lenalidomide 25 mg once per day on days 1-10, and ibrutinib 560 mg once daily continuously of each 21-day cycle (RLI). After two cycles, standard chemotherapy was added to RLI for six additional cycles. The primary end points were overall response rate (ORR) after two cycles of RLI alone and complete response rate after completion of RLI with chemotherapy. In evaluable samples, circulating tumor DNA and DLBCL90 assays were performed.RESULTSThe median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. The revised international prognostic index identified 42% as high risk, and 62% were double expressor of MYC and BCL2 protein. The ORR after two cycles of RLI was 86.2%, and the complete response rate at the end of RLI-chemotherapy was 94.5%. With a median follow-up of 31 months, the progression-free survival and overall survival were at 91.3% and 96.6% at 2 years, respectively.CONCLUSIONSmart Start is the first study, to our knowledge, to treat newly diagnosed DLBCL with a targeted therapy combination before chemotherapy. RLI produced a high ORR, and RLI with chemotherapy resulted in durable responses. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.
AB - PURPOSEChemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.METHODSWe enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m2 intravenous once on day 1, lenalidomide 25 mg once per day on days 1-10, and ibrutinib 560 mg once daily continuously of each 21-day cycle (RLI). After two cycles, standard chemotherapy was added to RLI for six additional cycles. The primary end points were overall response rate (ORR) after two cycles of RLI alone and complete response rate after completion of RLI with chemotherapy. In evaluable samples, circulating tumor DNA and DLBCL90 assays were performed.RESULTSThe median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. The revised international prognostic index identified 42% as high risk, and 62% were double expressor of MYC and BCL2 protein. The ORR after two cycles of RLI was 86.2%, and the complete response rate at the end of RLI-chemotherapy was 94.5%. With a median follow-up of 31 months, the progression-free survival and overall survival were at 91.3% and 96.6% at 2 years, respectively.CONCLUSIONSmart Start is the first study, to our knowledge, to treat newly diagnosed DLBCL with a targeted therapy combination before chemotherapy. RLI produced a high ORR, and RLI with chemotherapy resulted in durable responses. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.
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U2 - 10.1200/JCO.22.00597
DO - 10.1200/JCO.22.00597
M3 - Article
C2 - 35952327
AN - SCOPUS:85147012994
SN - 0732-183X
VL - 41
SP - 745
EP - 755
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -