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
Study Details
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.
Progression-Free Survival
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%.
KEY POINTS
- The addition of lenalidomide to R-CHOP improved progression-free survival among all patients with newly diagnosed DLBCL, including those with the ABC subtype.
- Myelosuppression was more common with lenalidomide plus R-CHOP.
Adverse Events
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.
