Abstract
Diffuse large-B-cell lymphoma (DLBCL) is the most frequent type of lymphoma which accounts for about 40 percent of new cases of lymphoma and more than 80 percent of aggressive lymphomas. It is reported to represent approximately 60 percent of all B-cell lymphomas in Eastern Asia and more than half of patients with DLBCL were found over 60 years old. The current first-line therapy is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) combined with Rituximab. However, positive effects of Rituximab use in the elderly were not certain before the year 2002 when clinical trials proved that it was more effective with Rituximab. However, the addition of Rituximab has brought more toxicities, thus a better medical care to prevent toxicities and weighing over toxicities and benefits should be carefully done before initiation of the RCHOP regimen in the elderly. It has been recognized now that DLBCL is a heterogeneous disease with different molecular characteristics, such as the germinal center B-cell (GCB) and non-GCB subtypes. Though both commonly seen in both Asia and the West, DLBCL has been reported to differ in some molecular characteristics. Studies revealed differences in the proportion of GCB and non-GCB DLBCL between Asian and Western patients. Whether this difference contributes to clinical treatment and response to the current RCHOP regimen still remains controversial. An overall similar outcome was observed in DLBCL elderly patients from both East Asia and West treated with RCHOP. However, more data is needed to determine the GC proportion, the benefits and toxicity files of RCHOP in Asian population.
A total of 84 elderly DLBCL patients who are 60 years old or older admitted to our center between 2009 and 2013 were included. Among them, 48 received CHOP with Rituximab and 36 received CHOP only chemotherapy due to economic reasons. No significant differences in gender, age distribution were found between the two groups. We stopped follow-up of these patients till May 2013. Overall survival time (OS), progression free survival time (PFS), GCB subtypes and toxicity files after chemotherapy were recorded. To better assess the stratification of IPI, we grouped these patients based on IPI score in two: IPI 0-1; 2; 3; 4-5 and IPI 0-2; 3-5. Cox-regression was performed for GCB subtypes, chemotherapy, different IPI groups, extranodal involvement with OS or PFS using SPSS 16.0 software. Kaplan-Meier survival curves also plotted between different factors with PFS or OS. P value less than 0.05 was considered significant.
In the four-group IPI scoring stratification system, the Cox regression model demonstrated a longer OS and PFS in Chinese elderly DLBCL patients treated with RCHOP than those receiving CHOP alone (p=0.014 and p<0.001). OS did not differ with GCB subtypes, extranodal involvement and the four IPI groups. PFS did not show difference with GCB subtypes, extranodal involvement, however, demonstrated an advantage in IPI group 1 (IPI=0 or 1) and group 2 (IPI=2). In the two-group IPI scoring stratification system, results showed a longer OS and PFS in patients treated with RCHOP (p=0.007 and p<0.001) and in patients with an IPI score less than 3 (p=0.002 and p=0.008). OS and PFS still did not differ with GCB subtypes, extranodal involvement. The estimated OS in these Chinese elderly DLBCL patients were 34.2 and 47.2 months in CHOP only group and RCHOP group while the PFS were 17.1 and 33.8 months respectively. 56% of the patients receiving RCHOP relapsed, but only 33% remission rate in CHOP only patients (p=0.048). Toxicities are more commonly seen in patients receiving RCHOP (p=0.013) including febrile neutropenia, infections, interstitial pneumonia and cardiomyopathy. Two patients receiving RCHOP even died with severe infection.
In the Chinese elderly patients diagnosed with DLBCL, IPI score can predict the OS and PFS when it is stratified into two group (0-2; 3-5). RCHOP use achieved longer OS and PFS than CHOP only regimen. No significant differences were observed in whether the patients have extranodal involvement or GCB subtype. However, Rituximab brought an increased risk of toxicities. In conclusion, Chinese elderly DLBCL patients achieved a longer OS and PFS with RCHOP than CHOP only regimen. However, clinicians should be aware of the toxicities which came along.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
