Combination of Lenalidomide with R-CHOP (R2CHOP) Is Well-Tolerated and Effective As Initial Therapy for Aggressive B-Cell Lymphomas - A Phase II Study

Lenalidomide was demonstrated to have significant single agent activity in relapsed aggressive B cell lymphoma (J Clin Oncol. 2008;26:4952–7, Ann Oncol. 2011;22:1622–7). In a phase I study, we previously demonstrated that Lenalidomide 25 mg day 1–10 of the cycle can be combined with RCHOP21 and this combination does not result in dose delays or increased toxicity (Leukemia 2011;12:1877–81). We now present phase 2 results of R2CHOP in treatment of patients with aggressive B-cell lymphoma.

Eligible patients were adults with newly diagnosed CD20 positive diffuse large B cell (DLBCL) or grade 3 follicular lymphoma (FL). The response was evaluated using PET/CT by standard criteria (J Clin Oncol. 2007;25:579–586). The progression free survival (PFS) was defined as time from diagnosis to disease progression or death.

51 patients - 6 enrolled at the MTD in phase 1 portion of the study and 45 in phase 2 portion were included in the analysis. The median age was 65 years (range, 19–87). 35% of patients were 70 and older. 63% (32/51) were males. 47 patients (92%) had DLBCL and 4 (8%) patients had FL grade 3. The international prognostic index (IPI) was low, low-intermediate, high-intermediate and high in 8 (15%), 18 (35%), 18 (35%) and 7 (14%) patients respectively. 31 patients (60%) had stage 4 disease. Hematological toxicities were: grade 3 and 4 thrombocytopenia (20% and 20% of patients respectively); grade 3 and 4 neutropenia (18% and 71% of patients respectively). Overall 27% of patients experienced a grade 3 or higher non-hematological toxicity at least possibly related to treatment. The most frequent were febrile neutropenia (10%), nausea (4%), urinary tract infection (4%), vascular access complication (4%), and dehydration (4%). 1 patient (2%) developed thrombosis. There was one death (2%) secondary to bowel perforation/sepsis. For 47 patients evaluable for response, the overall response (ORR) and complete response (CR) rates were 98% and 83% respectively. The PFS was 73% at 12 months (Figure). Since the enrolled patients represented a relatively high-risk group (49% intermediate high or high IPI, significant proportion of elderly male patients), the PFS in R2CHOP was compared to PFS in a contemporary cohort of 87 consecutive patients with DLBCL participating in Mayo Clinic Lymphoma Database and treated with standard RCHOP alone. The PFS was 62% at 12 months in this cohort and was inferior to R2CHOP (Figure).

Lenalidomide combined with standard R-CHOP21 chemotherapy (R2CHOP) demonstrates predictable safety profile. The ORR and CR rates and PFS are encouraging in elderly high IPI patients, and compared favorably to the R-CHOP treated historical cohort with similar clinical characteristics. A randomized trial will be needed to confirm the benefits of this novel combination.

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Off Label Use: lenalidomide in treatment of NHL. Reeder:Celgene: Research Funding. Ansell:Seattle Genetics, Inc.: Research Funding; Celgene Corporation: Consultancy.