In a phase II signal-seeking trial (ECOG-ACRIN E1412) reported in the Journal of Clinical Oncology, Grzegorz S. Nowakowski, MD, and colleagues found that the addition of lenalidomide (R) to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R2CHOP) improved outcomes in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), including those with the activated B-cell–like (ABC) subtype. As stated by the investigators, findings in preclinical studies and single-arm trials indicate that patients with the ABC disease subtype are particularly likely to benefit from the addition of lenalidomide to R-CHOP.
Grzegorz S. Nowakowski, MD
In the multicenter trial, 359 patients with stage II bulky to IV disease and International Prognostic Index (IPI) ≥ 2 were randomly assigned between August 2013 and January 2017 to receive six cycles of R2CHOP or R-CHOP. The efficacy-evaluable population consisted of 280 patients, including 145 in the R2CHOP group vs 135 in the R-CHOP group, including 44 vs 50 patients with the ABC subtype and 66 vs 56 with the germinal center B cell–like (GBC) subtype.
The co-primary endpoints were progression-free survival in all patients and in patients with ABC-DLBCL. One-sided significance levels were 0.1 for comparison among all patients and 0.125 for comparison among patients with ABC-DLBCL.
Median follow-up was 3.0 years. The study met its prespecified co-primary endpoints. Among all patients, R2CHOP vs R-CHOP was associated with improved progression-free survival (hazard ratio [hazard ratio] = 0.66, 95% confidence interval [CI] = 0.43–1.01), with 3-year rates of 73% vs 61% (P =.03). Among patients with ABC-DLBCL, the hazard ratio favoring R2CHOP was 0.64 (one-sided 90% CI upper limit = 1.01, two-sided 95% CI = 0.31–1.29, P = .1). Among patients with GCB-DLBCL, the hazard ratio was 0.82 (one-sided 90% CI upper limit = 1.27, two-sided 95% CI = 0.43–1.59).
Among all patients, R2CHOP was associated with improved overall survival, with 3-year rates of 83% vs 75% (HR = 0.67, P = .05). The objective response and compete response rates were 97% (P = .06) and 73% (P = .43) vs 92% and 68%.
Among the 166 R2CHOP and 171 R-CHOP patients constituting the safety population, the R2CHOP group had higher rates of grade ≥ 3 diarrhea (6% vs 1%, P = .005), anemia (29% vs 20%, P = .03), febrile neutropenia (25% v 14%, P = .003), thrombocytopenia (34% vs 13%, P < .001), and electrolyte abnormalities (5% vs 2%, P = .06). Treatment-related deaths occurred in two patients in the R2CHOP group and seven in the R-CHOP group. At time of analysis, secondary neoplasms had been observed in 12 vs 7 patients.
The investigators concluded, “In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL, including patients with ABC-DLBCL.”
Dr. Nowakowski, of the Division of Hematology, Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.