Grzegorz S. Nowakowski, MD
The addition of lenalidomide (Revlimid) to R-CHOP demonstrated promising efficacy in previously untreated patients with diffuse large B-cell lymphoma (DLBCL) across all subtypes of the disease, according to results from a phase II study published in the Journal of Clinical Oncology
Across 60 evaluable patients in the study, the overall response rate with lenalidomide plus R-CHOP (R2-CHOP) was 98%, with 80% of patients experiencing a complete response. Traditionally, patients with the non-germinal center B-cell-like (GCB) phenotype experience worse outcomes when treated with traditional R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). However, at a 24-month analysis, progression-free survival (PFS) rates in patients treated with R2-CHOP were 60% in non-GCB and 59% in GCB subtypes (P
= .83). The overall survival (OS) rates with the R2-CHOP regimen were 83% in non-GCB and 75% in GCB subtypes (P
“This study demonstrated that the addition of lenalidomide to conventional R-CHOP resulted in similar PFS rates and OS rates between subtypes,” Grzegorz S. Nowakowski, MD, an assistant professor of Medicine at the Mayo Clinic, said in a press release. “This is intriguing as patients with the non-GCB phenotype have traditionally experienced poorer outcomes. The results of this study support further evaluation of this regimen in this subtype of DLBCL.”
The phase II open-label study enrolled 64 patients with untreated stage II-IV CD20-positive DLBCL. Four patients dropped out of the trial prior to evaluation, primarily due to convenience issues. For comparison, 87 patients with DLBCL who had received treatment with conventional R-CHOP were selected from the Mayo Clinic Lymphoma Database. All selected patients were treated during a similar timeframe and met the same inclusion criteria as the 64 patients in the active study.
In the trial, lenalidomide was administered orally at 25 mg on days 1 through 10 of a 21-day cycle in combination with standard dose R-CHOP-21. Additionally, all patients received a 6-mg subcutaneous injection of pegfilgrastim on day 2 and low-dose daily aspirin, unless they were receiving blood thinners.
At a median follow-up of 23.5 months, the median duration of response had not yet been reached. In patients treated with R2-CHOP, the PFS rate was 59% and the OS rate was 78%. In the R-CHOP control, the PFS rate was 52% and the OS rate was 65%.
In the subtype analysis, outcomes were substantially superior for patients with non-GCB DLBCL treated with R2-CHOP compared with standard R-CHOP. For patients with the non-GCB subtype, the 24-month PFS rate was 60% with R2-CHOP compared with 28% with R-CHOP. Similarly, the 24-month OS rate was 83% with R2-CHOP compared with 46% for R-CHOP.
However, for patients with the GCB subtype, outcomes were similar between the two treatments. For this phenotype, the 24-month PFS rate was 59% with R2-CHOP compared with 64% with R-CHOP. Similarly, the 24-month OS rate was 75% with R2-CHOP compared with 74% for R-CHOP.
The most common grade 3/4 toxicities associated with R2-CHOP were neutropenia (88%), leukopenia (80%), and thrombocytopenia (44%). Grade 3 febrile neutropenia occurred in 9.4% of patients treated with R2-CHOP. One patient developed grade 5 sepsis, following the first cycle of therapy. Grade 3 nonhematologic toxicities were seen in 25% of patients.
"R2-CHOP is well tolerated, including in quite elderly patients," Nowakowski explained during a presentation of the study results at the 2014 ASCO Annual Meeting. "The efficacy of this combination appears to be promising when compared to R-CHOP therapy. It appears that the addition of lenalidomide may ameliorate the negative effect of the non-GCB phenotype on outcomes."
Findings from the phase II trial add to several early-stage clinical trials that have explored the addition of lenalidomide to R-CHOP across a variety of dosages. Additionally, studies have highlighted the efficacy and tolerability of the combination in elderly patients with DLBCL.
"Ultimately, randomized studies will be required to evaluate the efficacy of R2CHOP versus R-CHOP in the clinic for non-GCB patients," Nowakowski said during his presentation at ASCO. "One of these studies is ongoing—ECOG 1412—which randomizes patients to R2CHOP or R-CHOP and is open through the ECOG alliance or SWOG in the US."
The phase II ECOG 1412 study is actively recruiting patients with newly diagnosed DLBCL. Additionally, the phase III ROBUST trial that will assess R2-CHOP in patients with DLBCL is expected to begin enrollment in 2015, according to Celgene, the company that manufactures lenalidomide.