Abstract

Background

Therapeutic decision making for patients with low-grade (grade 1 and 2) FL involves deciding whether to treat, when to treat, and which among the numerous treatment modalities to administer. The lack of trials comparing outcomes of these treatment modalities makes it a complex process. This study seeks to examine the evolving treatment paradigm and evaluate the outcomes of first-line management strategies for low-grade FL in adults aged ≥ 66.

Methods

We used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 4,233 low grade FL patients (pts) aged 66 years and older diagnosed between 1995 and 2009. We ascertained first-line management strategies from Medicare claims made within 90 days of diagnosis. We used Kaplan-Meier estimators stratified by stage to evaluate survival functions for first-line management strategies. We used multivariate Cox proportional hazards models—stratified by stage and adjusted for patient demographics, comorbidity index, and year of diagnosis—to compare the impact of first-line management strategies on overall survival (OS).

Results

Of the 4,233 pts, 57% were female, 3% were African American, 93% were White, 51% resided in big metropolitan areas, 70% were diagnosed after 2000, 44% had stage III/IV disease, and 38% had extranodal involvement. The median age at diagnosis was 74 years (interquartile range 70-80). Common first-line management strategies were: observation (obs), 47%; chemotherapy (chemo) plus rituximab (R), 20%; chemo alone, 12%; R alone, 9%; and radiotherapy (XRT) alone, 9%. Among pts receiving chemo plus R (R-chemo), the most commonly used regimens were: R-CHOP (R, cyclophosphamide, doxorubicin, vincristine, and prednisone; 36%), R-CVP (R, cyclophosphamide, vincristine, and prednisone; 47%), R-Fludarabine based (9%), and R-other (7%).

The table displays median survival and hazard ratios (HRs) for first-line management strategies. Among stage I/II cases, most favorable outcomes were observed in cases receiving XRT alone, whereas among stage III/IV cases most favorable outcomes were observed in the group that received R-chemo. In the subset of stage III/IV pts that received R-chemo, R-CHOP was associated with the most favorable outcomes. HRs decreased steadily with increasing years of diagnosis.

Conclusion

First-line R-chemo is commonly used in older adults with low-grade FL in the United States and is associated with most favorable survival outcomes. XRT is associated with very favorable outcomes in stage I/II pts. Outcomes have improved steadily in the past 10 years.

Table

 All stages Stage I/II Stage III/IV 
 Median OS (yrs) HR (95% CI) Median OS (yrs) HR (95% CI) Median OS (yrs) HR (95% CI) 
Obs 7.62 Reference 8.24 Reference 6.85 Reference 
XRT 10.69 0.62 (0.52-0.75) 11.20 0.63 (0.51-0.79) 6.61 0.93 (0.60-1.44) 
Chemo 5.92 0.96 (0.79-1.17) 6.73 0.92 (0.68-1.26) 5.60 0.92 (0.70-1.21) 
R-chemo Not reached 0.71 (0.60-0.85) Not reached 0.64 (0.47-0.87) Not reached 0.71 (0.55-0.90) 
R 7.13 1.06 (0.89-1.30) 7.57 1.10 (0.83-1.45) 6.59 0.96 (0.75-1.24) 
 All stages   Stage I/II Stage III/IV 
Obs 7.62 Reference 8.24 Reference 6.85 Reference 
CVP 5.43 1.14 (0.86-1.5) 5.29 1.21 (0.78-1.90) 5.43 1.02 (0.69-1.52) 
CHOP 9.33 0.63 (0.43-0.92) Not reached 0.54 (0.30-0.96) 9.33 0.63 (0.35-1.13) 
R-CVP 8.65 0.77 (0.59-0.99) 8.06 0.76 (0.49-1.17) Not reached 0.74 (0.52-1.04) 
R-CHOP Not reached 0.52 (0.38-0.70) Not reached 0.42 (0.24-0.74) Not reached 0.56 (0.38-0.84) 
 All stages Stage I/II Stage III/IV 
 Median OS (yrs) HR (95% CI) Median OS (yrs) HR (95% CI) Median OS (yrs) HR (95% CI) 
Obs 7.62 Reference 8.24 Reference 6.85 Reference 
XRT 10.69 0.62 (0.52-0.75) 11.20 0.63 (0.51-0.79) 6.61 0.93 (0.60-1.44) 
Chemo 5.92 0.96 (0.79-1.17) 6.73 0.92 (0.68-1.26) 5.60 0.92 (0.70-1.21) 
R-chemo Not reached 0.71 (0.60-0.85) Not reached 0.64 (0.47-0.87) Not reached 0.71 (0.55-0.90) 
R 7.13 1.06 (0.89-1.30) 7.57 1.10 (0.83-1.45) 6.59 0.96 (0.75-1.24) 
 All stages   Stage I/II Stage III/IV 
Obs 7.62 Reference 8.24 Reference 6.85 Reference 
CVP 5.43 1.14 (0.86-1.5) 5.29 1.21 (0.78-1.90) 5.43 1.02 (0.69-1.52) 
CHOP 9.33 0.63 (0.43-0.92) Not reached 0.54 (0.30-0.96) 9.33 0.63 (0.35-1.13) 
R-CVP 8.65 0.77 (0.59-0.99) 8.06 0.76 (0.49-1.17) Not reached 0.74 (0.52-1.04) 
R-CHOP Not reached 0.52 (0.38-0.70) Not reached 0.42 (0.24-0.74) Not reached 0.56 (0.38-0.84) 

CVP–cyclophosphamide, vincristine, prednisone; CHOP- cyclophosphamide, doxorubicin, vincristine, prednisone

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.