Efficacy and Safety of Dose Attenuated CHOP Chemotherapy for Peripheral T-Cell Lymphoma in Elderly Patients

Background

Peripheral T-cell lymphoma (PTCL) is an uncommon disease entity that accounts for 10-15% of all non-Hodgkin lymphomas (NHL). Except for anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the median age of patients ranges between 5^th to 6^thdecades of life. Unfortunately, substantial numbers of the elderly patients are unable to tolerate full dose chemotherapy due to comorbidities or poor functional status. In this respect, we aimed to evaluate the efficacy and safety of the dose attenuated CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy in the elderly PTCL patients.

Methods

We analyzed data from patients with newly diagnosed PTCL aged over 65 years who presented to our institute between April 2001 and December 2014. NK/T cell lymphoma and mycosis fungoides were excluded from the study. Forty three patients were treated with the dose attenuated CHOP, which is a combination of cyclophosphamide (562.5 mg/m² for 1 day, 25% dose reduction from full dose), doxorubicin (37.5 mg/m² for 1 day, 25% dose reduction from full dose), vincristine (1.4 mg/m²for 1 day) and prednisolone (50 mg bid for 5 days).

Results

The median age was 72 years (range 65-86). Among the forty three patients, PTCL-not otherwise specified (NOS) accounted for 62.8% (n=27), AITL for 16.3% (n=7), ALK-negative ALCL for 11.6% (n=5), and enteropathy-associated T cell lymphoma (EATL) for 9.3% (n=4), respectively. Although 79.1% (n=34) of patients had good performance status (Eastern Cooperative Oncology Group (ECOG) performance status <2), 93.0% (n=40) were in advanced stage (> Ann Arbor stage II).

The overall response rate (ORR) and complete response (CR) rate was 77.8% and 52.8%, respectively. With a median follow-up period of 50.1 months (range 16.4-83.8), the 5-year event-free survival (EFS) and overall survival (OS) was 31.1% and 45.1%. The 5-year relapse-free survival (RFS) in those who achieved CR was 57.4%. Involvement of extranodal sites (≥2) (P=0.007 and hazard ratio [HR] 1.76 for OS, P=0.026 and HR 2.09 for EFS) was an independent prognostic factor for both EFS and OS.

The grade 3 and 4 adverse events were consistent with the expected toxic effects of CHOP chemotherapy. Grade 3 or 4 neutropenia and thrombocytopenia was observed in 71.4% and 19.0%, respectively. However, 45.2% experienced febrile neutropenia. In addition, twelve patients died from treatment-related toxicities. Another 10 died from progression of disease, and the other two from unknown causes.

Conclusion

Dose attenuated CHOP with 25% dose reduction of cyclophosphamide and doxorubicin for elderly PTCL doesn’t seem to diminish response or survival rates, which resulted in at least comparable efficacy outcomes to the prior reports (J Clin Oncol 2008;26:4124-4130). However, it is still associated with significant toxicities with high treatment-related mortalities. Novel treatment strategies for these vulnerable elderly patients are urgently needed.