A New Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Background

Elderly patients with diffuse large B-cell lymphoma (DLBCL) are more likely to face severe adverse events and/or insufficient dose intensity when treated with R-CHOP. The International Prognostic Index (IPI) predicts treatment outcome of patients with DLBCL, but risk stratification for such patients remains uncertain. Thus, we developed a new decision making model, which serves as a guide to the optimal personalized therapy for elderly DLBCL.

Patients and methods

This is a multicenter, retrospective study conducted by Society of Lymphoma Treatment in Japan (SoLT-J). Clinical features and treatment records of patients aged ≥ 65-years old, who had been diagnosed with de novo DLBCL and given at least one cycle of R-CHOP between 2001and 2012, were collected and analyzed for their prognostic significance after receiving approval from each institutional review board. Charlson Comorbidity Index (CCI) (Charlson et al, 1987) was used to access the co-existing medical status. Relative dose intensity (RDI) (i.e. the percentage of actual dose administered per protocol specified dose) for the average of cyclophosphamide and doxorubicin, adjusted by the effect of radiation therapy, was calculated for all patients.

Results

A total of 633 patients with a median 75-years old (range 65–96) treated with a median 6 cycles of R-CHOP (range 1–8) was analyzed. Ninety-six (15%) patients received planned or additional radiation therapy. R-CHOP therapy was discontinued in 129 (20%) patients because of treatment related toxicities, of which 30 (5%) patients died. The advanced age, hypoalbuminemia, and high score of CCI were identified as independent prognostic factors by the backward stepwise analysis for survival. The multivariate Cox regression analysis revealed that age > 75-years, serum albumin concentration < 3.7 g/dl, and CCI score ≥ 3 were significantly associated with worse overall survival (OS), progression free survival (PFS), and treatment related mortality (TRM), independently of IPI score ≥ 3 (Table 1). Regarding the index consisting of these three new risk factors, 135, 270, 184 and 44 patients were scored 0, 1, 2, and 3 point(s), respectively. The elevation of this score was significantly associated with lower average RDI (72% vs 63% vs 48% vs 41%, P < .0001) and more frequent unanticipated discontinuance of the treatment (10% vs 16% vs 31% vs 34%, P < .0001). Accompanied by IPI score ≥ 3, this index discriminated five risk groups with 3-year OS of 88%, 79%, 59%, 38%, and 6% (P < .0001), respectively (Figure 1).

Conclusion

The combination of age, serum albumin concentration, and comorbidities predicts adherence to R-CHOP—and outcome, as well as the IPI—in elderly patients with DLBCL. This prognostic model may help physicians to decide the intensity of the treatment, and needs to be validated further.

Table 1. Multivariate analysis for overall survival, progression free survival, and treatment related mortality.

	OS			PFS			TRM
Prognostic Factor	HR	P		HR	P		HR	P
Age > 75-years	2.16	<.0001*		1.99	<.0001*		2.20	0.0415*
Alb < 3.7 g/dl	2.28	<.0001*		1.88	<.0001*		3.90	0.0015*
CCI score ≥ 3	2.26	<.0001*		1.89	<.0001*		2.67	0.0185*
IPI score ≥ 3	1.72	<.0001*		1.87	<.0001*		1.71	0.1642