Grzegorz S. Nowakowski, MD from the Mayo Clinic speaks about the Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412.
Link To Study –
https://ascopubs.org/doi/full/10.1200/JCO.20.01375
Intent —
In untreated diffuse large B-cell lymphoma (DLBCL), lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) showed promising activity, particularly in the activated B-cell-like (ABC) subtype. A randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL was the Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412.
METHODS AND PATIENTS
Qualified and randomly allocated 1:1 to R2CHOP versus R-CHOP for six cycles were patients with newly diagnosed DLBCL, stage II bulky-IV illness, International Prognostic Index (IPI) ⇠2, and ECOG performance status ⇠2. Using the NanoString Lymph2Cx for cells of origin, tumors were examined. In all patients with co-primary endpoint PFS in ABC-DLBCL, progression-free survival (PFS) was the primary endpoint. Overall response rate (ORR), full response (CR) rate, and overall survival were the secondary endpoints (OS).
OUTCOMES
280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 were germinal center B-cell-like-DLBCL, 18 were unclassifiable, and 46 were unknown. Three hundred and forty-nine patients were enrolled. Baseline features were well-balanced between arms and the median age was 66 (range, 24-92); stage IV disease was present in 70 percent of patients; IPI 2, 3, and 4 or 5 were present in 34 percent, 43 percent, and 24 percent. In the R2CHOP arm, myelo-suppression was more normal. In R-CHOP, the ORR and CR rates were 92 percent and 68 percent and in the R2-CHOP arm, 97 percent (P = .06) and 73 percent (P = .43). R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an increase in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The median follow-up was 3.0 years. For ABC-DLBCL, the PFS HR for R2CHOP was 0.67. One-sided P = .1.
CONCLUSION
The addition of lenalidomide to R-CHOP (R2CHOP) in this signal-seeking research improved results in newly diagnosed DLBCL, including ABC-DLBCL patients.