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Adding Lenalidomide to R-CHOP Regimen Delivers a Punch to Diffuse Large B-Cell Lymphoma Subtype

Value-Based Care in Myeloma - Multiple Myeloma
Caroline Helwick

Lenalidomide (Revlimid) has changed the outcomes of patients with multiple myeloma, and it is showing promising efficacy as a therapy for another hematologic cancer, diffuse large B-cell lymphoma (DLBCL), especially within a poor-risk phenotype.

In a recent phase 2 study, the addition of lenalidomide to the standard R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) regimen (referred to as R2CHOP) reduced the negative prognostic significance of the non–germinal center B-cell (non-GCB) phenotype, producing progression-free survival (PFS) and overall survival (OS) rates similar to those observed in the GCB subtype (Nowakowski GS, et al. J Clin Oncol. 2014 Aug 18. Epub ahead of print).

Principal investigator Grzegorz S. Nowakowski, MD, of the Mayo Clinic, Rochester, MN, also presented the results of the R2CHOP study at the 2014 American Society of Clinical Oncology annual meeting, where he commented, “The addition of lenalidomide to conventional R-CHOP resulted in similar PFS rates and OS rates between sub-types. 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 sub-type of DLBCL.”

Advances in gene-expression profiling have revealed 2 major DLBCL subtypes—GCB and activated B-cell–like, which is better known as non-GCB. Although R-CHOP is the standard-of-care treatment for patients with advanced newly diagnosed DLBCL, the non-GCB subtype typically has a poor response to this or to any other treatment.

R2CHOP Study
The phase 2 clinical trial of R2CHOP included 64 patients newly diagnosed with stage II to IV DLBCL. The patients’ median age was 65 years, 20% were aged >70 years, 9% were aged >80 years, 60% had stage IV disease, and approximately 50% were considered high risk. “The inclusion criteria were designed to enroll patients similar to those seen in clinical practice,” the study authors indicated.

Among 60 patients who were evaluable for response, the response rate was 98%, with 80% of patients achieving a complete response. At 2 years, the overall event-free survival rate was 59%, and the OS rate was 78%.

A total of 87 patients in the Mayo Clinic lymphoma database met the same inclusion criteria and received R-CHOP alone; these patients served as historical controls for the analysis based on the DLBCL subtypes. The outcomes for the patients with the non-GCB phenotype who received conventional treatment were significantly worse than the outcomes in the GCB phenotype group and worse than the outcomes with R2CHOP, which essentially equalized the outcomes between the 2 subtype groups (Table).

There were no differences in the 24-month outcomes for patients receiving R2CHOP based on the non-GCB and GCB subtypes. The differences according to the 2 subtypes in the conventional arm were significant (P <.001 for both comparisons).

R2CHOP was well tolerated, even in the older patients in the study. Toxicity was mainly hematologic and was similar to the expected toxicity seen with R-CHOP alone. Although neutropenia was common (grade 3 or 4 occurred in 90% of patients), it was transient and was not associated with bleeding complications or with a need for platelet transfusion. Nonhematologic toxicities were uncommon.

“Good tolerability of the R2CHOP regimen was reflected by a large majority of patients who received the intended dose of therapy,” the researchers suggested. They concluded that the addition of lenalidomide to R-CHOP for 10 days of each R-CHOP cycle might overcome the negative prognostic impact that is associated with the non-GCB phenotype.

To validate these findings, the randomized ECOG 1412 clinical trial is currently comparing R2CHOP with R-CHOP for the initial treatment of patients with DLBCL.

Expert Commentary
Nathan Fowler, MD, of the University of Texas M.D. Anderson Cancer Center, who has led other studies of the R2CHOP regimen in lymphoma, commented in an interview with Value-Based Care in Myeloma that the novel regimen with lenalidomide shows “significant activity” in this patient population.

“This study further confirms the mounting preclinical evidence that lenalidomide has preferential antitumor activity in non–germinal center DLBCL cells,” Dr Fowler said, “and emphasizes the concept that adding a biologic agent to a chemotherapy backbone in the correct setting can translate into significantly improved outcomes.”

Table Outcomes for Non-GCB versus GCB Subtypes by Treatment

Outcome R2CHOP R-CHOP (controls)
24-month progression-free survival 60% (non-GCB) vs 59% (GCB) 28% (non-GCB) vs 64% (GCB)
24-month overall survival 83% (non-GCB) vs 75% (GCB) 46% (non-GCB) vs 78% (GCB)

GCB indicates germinal center B-cell; R-CHOP, rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone; R2CHOP, lenalidomide, rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone.

Source: Nowakowski GS, et al. J Clin Oncol. 2014 Aug 18 [Epub ahead of print].

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Last modified: May 20, 2015
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