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Racial differences in presentation and management of follicular non-Hodgkin lymphoma in the United States†
Report from the National LymphoCare Study
Article first published online: 20 MAR 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 19, pages 4842–4850, 1 October 2012
How to Cite
Nabhan, C., Byrtek, M., Taylor, M. D., Friedberg, J. W., Cerhan, J. R., Hainsworth, J. D., Miller, T. P., Hirata, J., Link, B. K. and Flowers, C. R. (2012), Racial differences in presentation and management of follicular non-Hodgkin lymphoma in the United States. Cancer, 118: 4842–4850. doi: 10.1002/cncr.27513
Presented in part as an oral session at the 49th Annual Meeting of the American Society of Hematology; December 8-11, 2007; Atlanta, Ga; and as an abstract and a poster at the 51st Annual Meeting of the American Society of Hematology; December 4-8, 2009; New Orleans, La.
- Issue published online: 19 SEP 2012
- Article first published online: 20 MAR 2012
- Manuscript Accepted: 1 FEB 2012
- Manuscript Revised: 25 JAN 2012
- Manuscript Received: 13 SEP 2011
- follicular lymphoma;
- racial disparities;
- African Americans;
- non-Hodgkin lymphoma
Racial differences in follicular lymphoma (FL) in the United States have not been investigated.
The National LymphoCare Study is a multicenter, longitudinal, observational cohort study collecting data on treatment patterns and outcomes for patients with newly diagnosed FL in the United States between 2004 and 2007 without any predefined, study-specific intervention. The authors investigated differences between white (W) patients, African American (AA) patients, and Hispanic (H) patients.
Among 2744 enrolled patients, there were 95 (3%) AA patients, 125 (5%) H patients, and 2476 (90%) W patients. Compared with W patients, more AA and H patients were diagnosed at age <45 years (P < .0001). H patients more commonly were diagnosed with grade 3 FL compared with AA and W patients (29%, 13%, and 18%, respectively; P = .019) and more commonly received rituximab plus chemotherapy as initial therapy compared with W patients (66% vs 50%; P = .036), while AA patients less commonly received anthracyclines (49% vs 64% in W patients; P = .027). H and AA patients who received rituximab plus chemotherapy were less likely than W patients to receive maintenance rituximab (27% vs 31% vs 40%, respectively; P = .031). At a median follow-up of 52 months, progression-free survival was similar between AA and W patients but was longer in H patients, and there was no difference in overall survival.
In the largest prospective cohort to date of AA and H patients with FL in the United States, AA and H patients were younger at presentation. Although racial differences in treatment patterns for FL were noted, additional follow-up is needed to determine the impact of these differences on survival. Cancer 2012. © 2012 American Cancer Society.
Follicular lymphoma (FL) is the second most common lymphoma in the United States, and approximately 14,000 patients are diagnosed annually.1 The disease is more prevalent among individuals of European descent compared with individuals of African, Hispanic, or Asian origin.2 Accordingly, most of our understanding of the presentation, clinical behavior, and outcomes associated with FL is based on Northern European and white American populations, because these patient groups are represented more in clinical trials and observational cohorts.
Patients with FL have a heterogeneous clinical course, but the Follicular Lymphoma International Prognostic Index (FLIPI) has been validated as a risk-stratification tool for predicting outcomes of patients undergoing treatment.3, 4 Choices of therapy often depend on disease stage, patient age, performance status, and therapeutic goals.5 Options include watchful waiting, involved-field radiotherapy, single-agent chemotherapy, monoclonal antibodies, and chemoimmunotherapy. It is noteworthy that several studies have demonstrated that the natural history of FL has improved significantly, especially since the introduction of rituximab.6-8 Rituximab-based combinations have become a recommended initial therapy in most patients when treatment is indicated.9 This approach has been widely adopted by the US oncology community, as described in the initial National LymphoCare Study (NLCS) report.10
Given the variability in behavior and prognosis of FL and the heterogeneity in front-line treatment of this disease, we sought to understand whether there were racial differences in disease presentation, patient characteristics, initial treatment strategies, and outcomes for FL patients in the United States. We specifically investigated whether differences in the use of rituximab, chemoimmunotherapy, or anthracyclines existed among different ethnic groups. We further analyzed whether these treatment variances impacted progression-free survival (PFS) and overall survival (OS). Although racial disparities have been reported in other malignancies,11, 12 disparities in presentation, care, and outcome rarely have been investigated in lymphoid cancers, largely because of the lower incidence in nonwhite populations.13 Recent studies indicate that, although the incidence of non-Hodgkin lymphoma (NHL) and most lymphoma subtypes is lower in individuals of African descent, black Americans with small lymphocytic lymphoma, diffuse large B-cell lymphoma, and Hodgkin lymphoma present more commonly with advanced-stage disease; and black patients in the latter 2 groups have worse survival outcomes.14-16 Another cohort study has suggested that, although African Americans were less likely to receive lymphoma therapy and had inferior all-cause and NHL-specific 5-year survival compared with Caucasians, these differences were best explained by differences in socioeconomic status.17 We sought to determine whether such differences in presentation and outcome were present among Americans diagnosed with FL.
MATERIALS AND METHODS
The NLCS Registry is a prospective cohort database study of patients with FL in the United States that was developed by Genentech, Inc. (South San Francisco, Calif) and Biogen Idec (Cambridge, Mass). The NLCS has an Advisory Board composed of academic investigators; some of whom coauthored this article (J.W.F., J.R.C., J.D.H., T.P.M., B.K.L., and C.R.F.). The Advisory Board participated in all phases of the study, including initial protocol design, prospective determination of data to be collected, and consideration of participating sites. The Advisory Board met quarterly, had full access to data listings, and collaborated with investigators (C.N.) and the sponsor regarding interpretation and publication of the data. This article is written de novo by the investigator and members of the Advisory Board.
Patients were recruited from academic and community oncology practices between March 2004 and March 2007. Final selection of academic and community sites was determined by study sponsors based on responses to a survey assessing a site's capability to participate in an observational study of FL. Questions included the number of patients annually with newly diagnosed FL, logistics, support for clinical research, and previous experience with sponsored clinical research. Data collection occurred as previously described.10 All patients signed a written informed consent for before participation, and the protocol was approved by a designated institutional review board in each institution. All patients who were within 6 months from their initial FL diagnosis and who had no prior history of lymphoma were eligible. There was no central pathology review; the local pathology report defined an FL diagnosis after investigator education on the World Health Organization classification system definitions of FL. Patients were evaluated and treated according to each physician's standard practice without study-specific treatments, visits, or evaluations required either at baseline or during the course of the study. Collected information included: demographics; clinical data (including performance status, disease stage, and the number of lymph node and extranodal sites); routine laboratory studies, including lactate dehydrogenase; serial management strategies; response to treatment as reported by the treating physician report only; and outcomes, including relapse and death.
Patients were assigned the highest documented stage when staging was incomplete. The treating physician documented each treatment program, including observation. Patients who did not receive therapy within 90 days of the diagnosis date were categorized in the observation group. Follow-up data regarding treatment and outcomes (including response, progression, and survival) were actively solicited from providers and collected quarterly. Enrolled patients are to be observed for up to 10 years from enrollment or until death, withdrawal of consent, or loss to follow-up. Enrollment sites were categorized as academic or community practices based on self-report.
Demographics, baseline disease characteristics, and initial treatment strategy, were summarized using descriptive statistics (medians and ranges for continuous variables and frequencies for categorical variables). Univariate associations among and between demographics, baseline disease characteristics, and initial treatment strategy were evaluated using a standard chi-square test or the Fisher exact test if required by sample size. The median PFS, defined as documented disease progression or death from any cause, was estimated using the Kaplan-Meier method, and unstratified log-rank P values are presented. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. All Cox regression models were adjusted for the number of extranodal sites, FLIPI group, histologic diagnosis, and investigator site type (academic vs community), except for models that analyzed anthracycline-treated patients vs nonanthracycline-treated patients, for which the investigator site type was replaced by geographic region. Both adjusted and unadjusted HRs are presented.
Patient Demographics and Disease Characteristics
Of 2744 enrolled patients, 2476 (90%) were white (W), 125 (5%) were Hispanic (H), 95 (3%) were African American (AA), and 48 (2%) either were of other ethnic background or their ethnicity was not recorded (Table 1). Patients were recruited from all US regions without major differences in racial distribution by region. Significantly more AA patients (25%) and H patients (22%) were aged <45 years at diagnosis compared with W patients (9%) (AA vs W, P < .0001; H vs W, P < .0001). H patients more often presented with grade 3 FL (as determined by the treating physician) compared with other racial groups (29% vs 13% for AA patients and 18% for W patients; H vs W, P = .019). Although disease stage did not differ significantly across racial groups, AA patients tended to have higher FLIPI scores at the time of presentation compared with W or H patients, although the difference was not statistically significant (AA vs W, P = .074). In fact, 47% of AA patients, 34% of W patients, and 30% of H patients had a poor-risk FLIPI score (≥3). Higher risk prognostic score was present more frequently in AA patients whether they were aged ≤60 years (29% AA vs 15% W vs 12% H) or aged >60 years (75% AA vs 51% W vs 56% H). No statistically significant differences were observed in other features at presentation. 1
|Characteristic||No. of Patients (%)||P|
|Whites, N = 2476||African Americans, N = 95||Hispanics, N = 125|
|Age, y||<.0001 [W vs AA, W vs H]|
|<45||229 (9.3)||24 (25.3)||28 (22.4)|
|45-59||843 (34.1)||32 (33.7)||40 (32)|
|60-74||911 (36.8)||25 (26.3)||43 (34.4)|
|≥75||493 (19.9)||14 (14.7)||14 (11.2)|
|Sex||.14 [W vs AA]; .17 [W vs H]|
|Men||1215 (49.1)||39 (41)||53 (42.4)|
|Women||1261 (50.9)||56 (59)||72 (57.6)|
|Stage||.78 [W vs AA]; .49 [W vs H]|
|I||431 (17.6)||13 (14)||22 (18)|
|II||379 (15.5)||12 (12.9)||18 (14.8)|
|III||713 (29.1)||28 (30.1)||43 (35.2)|
|IV||930 (37.9)||40 (43)||39 (32)|
|Grade||.06 [W vs AA]; .02 [W vs H]|
|1||1046 (42.3)||50 (53.2)||38 (30.7)|
|2||704 (28.5)||18 (19.2)||35 (28.2)|
|3||444 (18)||12 (12.8)||36 (29)|
|Unknown||232 (9.4)||13 (13.8)||12 (9.7)|
|Mixed||48 (1.9)||1 (1.1)||3 (2.4)|
|FLIPI scorea||.07 [W vs AA]; .70 [W vs H]|
|Good||718 (35.7)||19 (27.1)||31 (36.1)|
|Intermediate||607 (30.2)||18 (25.7)||29 (33.7)|
|Poor||685 (34.1)||33 (47.1)||26 (30.2)|
|>4 Lymph node areas||811 (34.2)||36 (40)||27 (23.1)||.25 [W vs AA]; .01 [W vs H]|
|Elevated LDH||398 (20.8)||17 (25.8)||26 (31.3)||.33 [W vs AA]; .02 [W vs H]|
|Age ≤60 y||1141 (46.1)||57 (60)||73 (58.4)||<.01 [W vs AA]; <.01 [W vs H]|
|Stage III or IV||1643 (67)||68 (73.1)||82 (67.2)||.22 [W vs AA]; .96 [W vs H]|
|Hgb <12 g/dL||457 (19.6)||33 (40.2)||37 (32.2)||<.0001 [W vs AA]; <.01 [W vs H]|
|B-symptoms||.30 [W vs AA]; .43 [W vs H]|
|Yes||621 (25.1)||28 (29.8)||35 (28.2)|
|No||1853 (74.9)||66 (70.2)||89 (71.8)|
Similar percentages of AA patients and W patients received rituximab monotherapy, chemotherapy alone, or rituximab plus chemotherapy (Table 2). H patients were more likely to receive rituximab plus chemotherapy than either AA patients or W patients (66% H vs 54% AA vs 50% W). In the AA group, 51 patients (54%) received rituximab plus chemotherapy, including 15 patients (29%) who received combined rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) and 19 patients (37%) who received the same drugs plus doxorubicin (R-CHOP). In the W group, 1231 patients (50%) received rituximab plus chemotherapy, including 284 patients (23%) who received R-CVP and 653 patients (53%) who received R-CHOP. Although the difference in receipt of R-CHOP/R-CVP was not statistically significant (AA vs W, P = .082), fewer AA patients who received rituximab plus chemotherapy also received anthracyclines compared with their counterparts (49% AA, 64% W; P = .027). The difference in receipt of anthracyclines was more evident in patients aged <60 years (50% AA vs 71% W vs 67% H; P = .049), whereas it was not apparent in those aged ≥60 years (48% AA vs 57% W vs 50% H; P = .48). Furthermore, the difference in receipt of anthracyclines persisted in patients who had poor-risk FLIPI scores (61% W vs 40% AA; P = .056) and in patients who had grade 1 or 2 FL (56% W vs 41% AA; P = .086), but the difference was statistically significant. No significant difference in the receipt of anthracyclines was observed in patients who had grade 3 FL (82% W vs 70% AA; P = .35), although the numbers of patients with grade 3 FL was small (12 AA patients vs 444 W patients). No major differences were noted between H patients and W patients regarding the receipt of anthracyclines (60% W vs 64% H; P = .46).
|Treatment||No. of Patients (%)||P|
|Whites, N = 2476||African Americans, N = 95||Hispanics, N = 125|
|Regimen||2474||94||124||.88 [W vs AA]; .04 [W vs H]|
|Watchful waiting||437 (17.7)||17 (18.1)||19 (15.3)|
|Rituximab monotherapy||349 (14.1)||12 (12.8)||10 (8.1)|
|Chemotherapy||79 (3.2)||3 (3.2)||5 (4)|
|Rituximab and chemotherapy||1231 (49.8)||51 (54.3)||82 (66.1)|
|R-CHOP||653 (53.1)||19 (37.3)||40 (48.8)|
|R-CVP||284 (23.1)||15 (29.4)||20 (24.4)|
|R-other||293 (23.8)||17 (33.3)||22 (26.8)|
|Othera||378 (15.3)||11 (11.7)||8 (6.5)|
|Combination chemotherapy||.03 [W vs AA]; .46 [W vs H]|
|Anthracycline-based||803 (64)||26 (49.1)||51 (60)|
|Nonanthracycline based||452 (36)||27 (50.9)||34 (40)|
There were no significant racial differences in receipt of anthracyclines observed in academic institutions (57% AA vs 63% W vs 81% H; P = .22), although the receipt of anthracyclines was more frequent in W patients when the were treated in a community setting (receipt of anthracyclines, 46% AA vs 64% W vs 52% H; P = .015)
Investigator-coded overall response rates were similar across the racial groups for patients who received rituximab monotherapy, rituximab plus chemotherapy, and chemotherapy alone (Table 3). However, when initial treatment strategies were pooled for all patients who received front-line therapy, W patients had a higher response rate than AA patients (72% vs 67%, respectively; P = .039), whereas W patients and H patients had similar response rates (75% H; P = .84).
|Response||No. of Complete/Partial Responses (%)||P|
|Whites, N = 2476||African Americans, N = 95||Hispanics, N = 125|
|Any treatment received||1784/2470 (72)||62/94 (66)||93/124 (75)||.04 [W vs AA]; .84 [W vs H]|
|Rituximab monotherapy||273/349 (78)||8/12 (67)||8/10 (80)||.24 [W vs AA]; .80 [W vs H]|
|Rituximab and chemotherapy||1089/1230 (89)||45/51 (88)||70/82 (85)||.18 [W vs AA]; .65 [W vs H]|
Maintenance therapy with rituximab in patients who were induced with rituximab plus chemotherapy was used less commonly in AA and H patients compared with W patients (31% AA vs 40% W vs 27% H; P = .031) (Table 4). In patients who were induced with rituximab monotherapy, the rate of rituximab maintenance was similar for the 3 groups (42% of AA patients, of 41% W patients, and 40% of H patients; P = 1.00).
|Regimen||No. of Patients (%)||P|
|Whites, N = 2476||African Americans, N = 95||Hispanics, N = 125|
|Observation||205 (58.7)||7 (58.3)||6 (60)|
|Maintenance||144 (41.3)||5 (41.7)||4 (40)|
|Observation||738 (60)||35 (68.6)||60 (73.2)|
|Maintenance||493 (40)||16 (31.4)||22 (26.8)|
|R-chemotherapy or R induction||1580||63||92||.04|
|Observation||943 (59.7)||42 (66.7)||66 (71.7)|
|Maintenance||637 (40.3)||21 (33.3)||26 (28.3)|
Progression-Free and Overall Survival
At a median follow-up of 52 months, the median PFS was 51 months for AA patients, 68 months for W patients, and not reached for H patients (H vs AA, P = .006; H vs W, P = .024; log-rank test). Given the long natural history of FL and the relatively short follow-up, these results should be interpreted with caution, because only 27% of H patients, 40% of W patients, and 45% of AA patients had an event as of the date of data cutoff (November 2010). The PFS advantage in H patients remained evident in individuals who received anthracyclines, but not in those who did not. No difference in PFS was observed among the 3 races among the patients who were on observation, received rituximab monotherapy, or received rituximab plus nonanthracycline-based chemotherapy. OS was similar for all 3 racial groups (Table 5).
|PFS: Median follow-up 52 months|
|White (N = 2470)||African American (N = 94)||Hispanic (N = 124)|
|Number of events No. (%)||996 (40%)||42 (45%)||33 (27%)|
|Median PFS||67.6 (62.0–70.7)||51.1 (34.1–NR)||NR (NR–NR)|
|Months (95% CI)||P = 0.16 (vs. W)||P = 0.02 (vs. W)|
|Log rank P-value||P <0.01 (vs. AA)|
|Unadjusted HR (95% CI)||1.25 (0.92–1.70) (vs. W)||0.67 (0.48–0.95) (vs. W)|
|0.54 (0.34–0.85) (vs. AA)|
|Adjusted HRa (95% CI)||1.13 (0.83–1.54) (vs. W)||0.72 (0.51–1.01) (vs. W)|
|0.64 (0.40–1.00) (vs. AA)|
By using the NLCS, our report is the first to our knowledge examining racial differences in disease presentation, characteristics, treatment selection, responses, and outcomes in a prospective cohort of US patients with FL. The importance of this analysis is reflected in the facts that FL is heterogeneous and that our current treatment approaches are based on clinical trials in which AA patients and H patients were under represented. Although emerging data indicate that AA patients with other lymphoid malignancies present at a younger age, with more advanced stage disease, and have inferior survival compared with other racial/ethnic groups,14-16, 18 and although other studies suggest that there are racial and socioeconomic differences in the use of lymphoma therapies in the United States,17 it may be hypothesized that such differences in patients with FL also exist. The NLCS offers the unique opportunity to prospectively study patterns of care in FL patients and how such variability in delivering care impacts outcome.
We identified 95 patients AA and 125 H patients in the NLCS who were treated between 2004 and 2007, when modern treatment regimens and targeted therapies were available, making the data relevant to current practice. To our knowledge, this represents the largest prospective collection of data in these populations reported in the US to date. We observed that more AA and H patients presented with FL at a young age (<45 years) and with high-risk FLIPI compared with W patients. Data from the Surveillance, Epidemiology, and End Results (SEER) Program from that same period support the finding that AA patients with FL are diagnosed at a younger age than W patients (median age, 57 years vs 64 years; P < .001).19 Differences in age at presentation cannot be explained with current data but raise the possibility that environmental and occupational factors in certain ethnicities may be causative. Although an argument could be made that lower hemoglobin values from noncancer causes (thalassemia and sickle cell traits) may account for the higher percentage of poor-risk FLIPI scores in AA patients, the finding that more AA patients were aged <45 years supports the significance of the high-risk FLIPI scores in this population. This difference in age distribution is not limited to FL, because AA patients with diffuse large B-cell lymphoma, small lymphocytic lymphoma, and Hodgkin lymphoma also present at a younger age; and their outcomes appear to be inferior to the outcomes of their W counterparts.14-16 Another notable difference was that H patients presented more commonly with grade 3 FL compared with AA and W patients (H vs W, P = .0186). However, this finding should be interpreted with caution, because there was no central pathology review to confirm the grade, and variability in establishing the grade in patients with FL has been reported in prior studies.20 With modern techniques, agreement between expert pathologists can be high,21, 22 so these findings should be confirmed with additional studies. These racial differences in the incidence of grade 3 FL may have important therapeutic implications given the controversy regarding how to treat these patients.23-25 Also, our patients were not subcategorized into grade 3a or 3b disease, a distinction that also remains controversial in terms of its clinical significance.26
Because of previous observations that treatment selection varies based on oncologists' geographic location,27 we evaluated whether treatment patterns among W patients, AA patients, and H patients varied based on the location of the treating practice (West, Northeast, Midwest, Southwest, and Southeast). We did not observe any notable difference, although small sample sizes for each region make detection of differences difficult (data not shown). We determined that fewer AA patients received anthracycline-based chemotherapy compared with their W counterparts (49% vs 64%; P = .0271). Although the role of anthracyclines in the front-line treatment of FL is debatable, R-CHOP was the most used first-line regimen among US oncologists during the study time.10 The current study indicates that AA patients received R-CHOP less often despite the finding that AA patients were younger and had higher FLIPI scores at presentation. Several explanations could account for this difference, such as higher rates of cardiac dysfunction, which may be more common in AA patients, the patient's preference, physician bias, or other factors. However, the detailed rationale for treatment selection was not captured and remains theoretical. It remains debatable whether our data indicate under use of anthracyclines in AA patients, overuse of anthracyclines in W patients, appropriate use in each population based on their age distributions, or some other phenomenon. Patterns of access to care and insurance coverage among the different groups may in part explain these differences. Nevertheless, understanding the patterns anthracyclines use in FL is important, because long-term toxicities of these agents may affect the overall outcome. In addition, the theory that anthracyclines affect FL transformation28 eventually could be validated as we observe, with longer follow-up, whether anthracyclines-treated patients have less incidence of transformation. Also, we observed that H patients were more likely to receive rituximab plus chemotherapy than either W patients or AA patients. It is noteworthy that most patients were treated at the time of their initial diagnosis, and <20% were observed across all racial groups.
When analyzing responses, the overall response rates were similar across all racial groups regardless of the treatment received. It is noteworthy that responses were not assessed centrally and were not required at predefined intervals, as is usual in prospective clinical trials; responses were recorded as reported by treating physicians. This may have limited our ability to accurately compare data regarding PFS and OS by race. Among the patients who received rituximab and chemotherapy, 89% of W patients, 88% of AA patients, and 85% of H patients experienced a treatment response. It is reassuring that the reported response rate was similar to what has been published in randomized studies.29 It also is noteworthy that responses were similar despite the heterogeneity in anthracycline use, arguing for additional prospective randomized studies to establish whether anthracyclines have a role in front-line FL therapy. This was reinforced by data indicating that the combination of bendamustine and rituximab produced superior PFS and had a better toxicity profile compared with R-CHOP.30 Additional follow-up of the NLCS and other studies are needed to assess not only the proximal effects of treatments on toxicity, response, and PFS but also the downstream effects of the ability to deliver additional therapies, later line toxicities, quality of life, and OS.
Albain et al reviewed racial disparities in survival among cancer patients enrolled on prospective Southwest Oncology Group studies between 1974 and 2001.31 In their review, of 19,457 patients, 1291 had lymphoid malignancies. Although AA patients with other cancers had worse survival, such a difference was not witnessed in patients with lymphoma. However, that investigation focused on survival without addressing patterns of care, did not examine lymphoma histologic subtypes, and was subject to selection bias, because it was based only on cooperative group trial enrollment.31 Han et al reported on 254,702 cases of lymphoid neoplasm diagnosed from 1973 to 2003 at SEER sites.32 In that report, non-Hispanic W patients typically had higher survival rates than AA patients with the exception of patients with multiple myeloma. In another population-based study of Hodgkin lymphoma, AA patients and H patients had an increased risk of disease-related death regardless of the age group studied.33 These differences in lymphoma survival patterns suggest that distinct prognostic risk factors have an impact on survival according to subtype, supporting research and public health interventions to address racial disparities in lymphoma survivorship.
Although the median follow-up of our current study, 52 months, was relatively short in the natural history of FL, important observations emerged. Longer PFS was observed in H patients compared with W and AA patients (median not reached vs 68 months for W patients [P = .024] and 51 months for AA patients [H vs AA, P = .0063]). It is noteworthy that the witnessed PFS advantage for H patients was observed only in the subgroup that received anthracyclines. The observed difference in PFS among H patients, despite a lack of any difference in the response rate, requires further examination. In addition, the infrequent receipt of anthracyclines in AA patients and the similar PFS for those AA patients and their W counterparts raise an important issue regarding whether anthracyclines are needed in patients with FL. Understanding the patterns of use of these agents and the potential benefits or harms from their wide applications is very important as we move the field forward. It is noteworthy that the witnessed PFS advantage in H patients occurred even though higher numbers of W patients received maintenance rituximab compared with H patients, suggesting a possible true advantage for the H patient population. Also, the lack of a PFS advantage in W patients compared with AA patients, despite the more frequent receipt of maintenance therapy in W patients, requires further study. It is important to highlight that any detected differences in PFS may have occurred because of variability in follow-up evaluations that potentially may lead to delayed detection of progressive disease.
Despite the limitations of the observational design, the NLCS provides important prospective information on FL patients treated in community and academic practices in the United States. Furthermore, the NLCS is less subject to patient selection, because there are no treatment requirements; thus, it is not biased by the referral patterns observed in large, randomized studies, enhancing the external validity of these results. Our report indicates for the first time that racial differences in disease presentation, characteristics, and care for patients with FL exist in the United States. Additional follow-up is needed to determine whether these differences will translate into differences in future outcomes.
No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES
Chadi Nabhan receives research funding from Genentech and is a member of the Genentech Speakers' Bureau; Christopher R. Flowers is a consultant for Genentech (unpaid), Allos, Celgene, Spectrum, and Seattle Genetics and receives research funding from Novartis, Millennium, Celgene, and Spectrum. Jonathan W. Friedberg participates in Advisory Board activities for Genentech; Michelle Byrtek, Jamie Hirata, and Michael D. Taylor are employed by Genentech/Roche, and all own stock options in Roche; Brian K. Link, James Cerhan, Thomas P. Miller, John D. Hainsworth, Jonathan Friedberg, and Christopher R. Flowers are members of the Advisory Board of the National LymphoCare Study.
- 3The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome. Blood. 2006; 108: 1504-1508., , , , , .
- 9NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010; 8: 288-334., , , et al.
- 13Racial differences in the incidence and outcomes for patients with hematological malignancies. Curr Probl Cancer. 2007; 31: 182-201., , , .
- 14Incidence patterns and outcomes for Hodgkin lymphoma patients in the United States [serial online]. Adv Hematol. 2011; 2011: 725219., , , .
- 15Racial differences in the presentation and outcomes of diffuse large B-cell lymphoma in the United States [published online ahead of print December 22, 2010]. Cancer. 2010., , , et al.
- 22Expert second opinion pathology review of lymphoma in the era of the World Health Organization classification [abstract]. Blood (ASH Annual Meeting Abstracts). 2007; 110. Abstract 3317., , , et al.
- 27Correlates of treatment intensity for initial management of follicular lymphoma (FL) in the United States: report from the National LymphoCare Study (NLCS) [abstract]. Blood (ASH Annual Meeting Abstracts). 2007; 110. Abstract 2612., , , et al.
- 30Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany) [abstract]. Blood (ASH Annual Meeting Abstracts). 2009; 114. Abstract 405., , , et al.