R-THP-COP demonstrates similar clinical activity to R-CHOP but appears to have a more favorable toxicity profile in elderly newly diagnosed DLBCL patients

In the journal Internal Medicine, Hiroaki Araie from the University of Fukui, Japan, and colleagues published findings from their retrospective single-center study, which aimed to compare the efficacy and toxicity of R-THP-COP (rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone) with R-CHOP in newly diagnosed patients with Diffuse Large B-Cell Lymphoma (DLBCL) who are aged 65 years or older.

Patients who were admitted to the University of Fukui Hospital from 2004 to 2013 were included in this retrospective analysis (n=98). Pathological findings from samples and PET/CT was used to reach diagnoses. The primary outcome measure of the study was response rate after chemotherapy and secondary measures included 2-year OS, 2-year PFS, and AEs.

Key Highlights:

Treatment:

• R-CHOP: 6–8 cycles every 21 days - 375mg/m² rituximab on day 1; 50mg/m² doxorubicin on day 1; 750mg/m² cyclophosphamide on day 1; 1.4mg/m² vincristine on day 1, and 100mg prednisolone on days 1–5
• R-THP-COP: 6–8 cycles every 21 days - 375mg/m² rituximab on day 1; 50mg/m² THP on day 1; 750mg/m² cyclophosphamide on day 1; 1.4 mg/m² vincristine on day 1; and 100mg prednisolone on days 1–5

Patients:

• Median age = 76 years (range, 65–90); male = 39; R-CHOP = 45 (60.1%); R-THP-COP = 29 (39.9%)
• Mean PS was higher in pts treated with R-THP-COP than R-CHOP (1.5 vs 1; P = 0.31)
• Median age was higher in pts treated with R-THP-COP than R-CHOP (77 vs 74; P = 0.01)
• Cardiac dysfunction was more common in pts treated with R-THP-COP (n=3) than R-CHOP (n=0)
• The most common comorbidities in the R-CHOP and R-THP-COP arms were hypertension (n=19) and diabetes mellitus (n=5), respectively
• Both arms had a median number of 6 cycles administered
• Mean Relative Dose Intensity (RDI) for R-THP-COP and R-CHOP was 70.8% and 74.8%, respectively (P = 0.50)

Efficacy:

• Overall: ORR = 94.6%; CR = 86.4%; PR = 8.1%
• R-THP-COP: CR = 79.3%; PR = 13.8%
• R-CHOP: CR = 91.1%; PR = 4.4%
• No difference in ORRs found between the 2 arms (P = 0.64)
• Median follow-up = 38.5 months
• 2-year OS for R-THP-COP and R-CHOP was 77.6% and 79.2%, respectively
• 2-year PFS for R-THP-COP and R-CHOP was 68.5% and 78.9%, respectively
• No significant difference found for OS (P = 0.629) or PFS (P = 0.433)
• In both arms, 2-year OS was significantly improved in RDI≥70% (87.0%) versus RDI<70% (58.2%; P = 0.027)
• In the R-THP-COP arm, 2-year OS in pts with RDI≥70% was higher than in those with RDI<70% (93.3% vs 8%; P < 0.01)
• Univariate analysis identified PS, clinical stage, IPI, LDH, and soluble interleukin 2 receptor level as prognostic factors for OS
• Multivariate analysis identified PS as an independent prognostic factor for OS (HR = 3.9; 95% CI, 1.4–10.8; P < 0.001)

Toxicity:

• Most common AE in R-THP-COP and R-CHOP arms was neutropenia (72.4% and 88.9%, respectively; P = 0.07)
• In R-THP-COP and R-CHOP arms, febrile neutropenia was experienced by 31.0% and 44.4% of pts, respectively
• G-CSF administered to 55.2% (16/29) and 71.1% (32/45) R-THP-COP and R-CHOP pts, respectively (P = 0.16)
• Mean neutropenia grade was 3.6 and 3.3 for R-CHOP and R-THP-COP, respectively (P = 0.08)
• No significant difference observed in incidence of AEs between therapy arms
• No treatment-related deaths reported for either arm

The authors concluded that R-THP-COP demonstrated similar clinical activity to R-CHOP but appears to have a more favorable toxicity profile. The group also state that their findings emphasize the importance of maintaining RDI, even in elderly DLBCL patients. Lastly, they state that swapping adriamicin to THP (which has less cardiotoxicity than adriamicin) can “effectively and safely maintain the RDI, thereby improving the clinical efficacy, even in old patients with DLBCL.” 

Abstract:

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m², day 1) -THP-COP (pirarubicin 50 mg/m² day 1, cyclophosphamide 750 mg/m² day 1, vincristine 1.4 mg/m² day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m² day 1, cyclophosphamide 750 mg/m² day 1, vincristine 1.4 mg/m² day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles. Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen. Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.