The authors of a single-center, real-world study in Turkey found that patients with diffuse large B-cell lymphoma (DLBCL) who received the rituximab biosimilar Redditux had similar overall survival as did patients in a historical control group who had received the reference product (Rituxan).

However, progression-free survival was longer in the historical control group, and the authors say pharmacokinetic differences could be responsible.

DLBCL is the most common type of non-Hodgkin lymphoma. According to the authors, the addition of rituximab, a chimeric antibody targeting the B cell surface antigen CD20, to DLBCL therapy has significantly improved response rates.

The rituximab biosimilar Redditux was approved in Turkey in March 2018 for all indications of the reference product. The center investigated effectiveness and safety of Redditux in its patients after switching from the reference product to the biosimilar for cost savings.

According to the investigators, there are “scarce” relevant clinical trials and real-world studies on Redditux in hematological malignancies such as DLBCL. At their center, 51 patients were treated with the rituximab biosimilar and chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The patients were compared to a historical control group of 219 patients who had been treated with the reference product plus CHOP. All patients had been newly diagnosed with DLBCL and were treated with a median of 6 cycles of rituximab plus CHOP.

The median follow-up time was significantly different between groups: 31 months (range 8-39) in the biosimilar and 38 (range 1-106) in the historical control group. The percentage of patients with Eastern Cooperative Oncology Group (ECOG) performance score > 1 was also significantly different, 15 patients (29.4%) in the biosimilar group compared to 30 patients (13.7%) in the historical control group treated with the reference product.

Overall response rates (ORRs) were similar between groups. The ORR in the biosimilar cohort was 86%; 37 patients (72.5%) had a complete response (CR) and 7 (13.5%) had a partial response (PR). In the historical control group, ORR was 84%, with 82% of patients having a CR, and 2% a PR. Fourteen percent of patients in the biosimilar group had refractory disease, compared to 15.6% in the historical control group.

The 24-month progression-free survival (PFS) rates were significantly different between groups, at 74% (95% CI, 0.59-0.84) in the biosimilar group and 85% (95% CI, 0.79-0.90) in the historical control group. Higher PFS rates were also found in the historical control group in subgroup analysis of patients with high revised International Prognostic Index scores and using nearest neighbor matching analysis to match biosimilar and reference product-treated patients based on age range, gender, DLBCL cell type, disease stage, lactate dehydrogenase level, ECOG performance score, and number of extranodal sites. Central nervous system relapse was also higher in the biosimilar group (10% vs 1.83%), with bone involvement at the time of diagnosis a risk factor.

According to the investigators, the observed differences in PFS could be due to pharmacokinetics. In their preliminary analysis of these 2 groups of patients, population pharmacokinetics showed that the volume of the central compartment was approximately 0.95 L in the biosimilar group and between 1.8 L and 3.9 L in the historical control group. They also said other researchers have calculated the half-life of Redditux as much shorter than that of the reference product, 11 days compared with 20-100 days.

Safety results could not be compared between groups, the authors said, due to missing data for the patients in the historical control group. However, in the biosimilar group, the most common adverse event (AE) was neutropenia in 39% of patients. Twenty percent of patients experienced grade 2 infusion reactions requiring medical attention. Grade 3 and 4 AEs included leukopenia in 4% of patients, anemia in 12% of patients, and thrombocytopenia in 6% of patients. The authors added that no serious adverse events resulted in cessation of rituximab therapy.

The authors concluded that the patients treated with the rituximab biosimilar Redditux at their center had similar OS rates compared to those in a historical control group who had been treated with that originator. However, PFS rates were inferior in the biosimilar group, which could be attributable to pharmacokinetic differences. They said head-to-head pharmacokinetic comparisons, as well as large prospective and real-world studies with longer follow-up duration are necessary to confirm similar effectiveness and safety of Redditux compared to the reference product.

Source:- Center For Biosimilar