Early-stage Nodular Lymphocyte-predominant Hodgkin Lymphoma Research Articles

Interim PET-guided treatment for early-stage NLPHL: a subgroup analysis of the randomized GHSG HD16 and HD17 studies

AbstractThe optimal first-line treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) diagnosed in early stages is largely undefined. We, therefore, analyzed 100 NLPHL patients treated in the randomized HD16 (early-stage favorable; n = 85) and HD17 (early-stage unfavorable; n = 15) studies. These studies investigated the omission of consolidation radiotherapy (RT) in patients with a negative interim positron emission tomography (iPET) (ie, Deauville score <3) after chemotherapy (HD16: 2× doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]; HD17: 2× escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP] plus 2× ABVD). Patients with NLPHL treated in the HD16 and HD17 studies had 5-year progression-free survival (PFS) rates of 90.3% and 92.9%, respectively. Thus, the 5-year PFS did not differ significantly from that of patients with classical Hodgkin lymphoma treated within the same studies (HD16: P = .88; HD17: P = .50). Patients with early-stage favorable NLPHL who had a negative iPET after 2× ABVD and did not undergo consolidation RT tended to have a worse 5-year PFS than patients with a negative iPET who received consolidation RT (83% vs 100%; P = .05). There were 10 cases of NLPHL recurrence. However, no NLPHL patient died during follow-up. Hence, the 5-year overall survival rate was 100%. Taken together, contemporary Hodgkin lymphoma-directed treatment approaches result in excellent outcomes for patients with newly diagnosed early-stage NLPHL and, thus, represent valid treatment options. In early-stage favorable NLPHL, consolidation RT appears necessary after 2× ABVD to achieve the optimal disease control irrespective of the iPET result.

T020: Interim PET-guided treatment of early-stage nodular lymphocyte-predominant Hodgkin lymphoma: a subgroup analysis of the GHSG HD16 and HD17 studies

Background: The optimal treatment for patients with early-stage nodular-lymphocyte predominant Hodgkin lymphoma (NLPHL) other than stage IA is undefined. Patients and Methods: We investigated characteristics and outcomes of patients with early-stage NLPHL (favorable: 85 patients; unfavorable: 15 patients) who had treatment within the randomized GHSG HD16 and HD17 studies. Results were compared to those from patients with classical Hodgkin lymphoma (cHL) (favorable: 495 patients; unfavorable: 764 patients) treated within the same studies. Chemotherapy consisted of 2 cycles of ABVD (HD16) or 2 cycles of escalated BEACOPP plus 2 cycles of ABVD („2 + 2“) (HD17). In the experimental study arms, consolidation radiotherapy (RT) was applied on the basis of the result of interim positron emission tomography (PET-2). In the standard arms, consolidation RT was mandatory. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: In the HD16 and HD17 studies, 62/85 (73%) and 13/15 (87%) NLPHL patients were male as compared to 254/495 (51%) and 337/764 (44%) cHL patients. The median age of patients with NLPHL was 37 years in the HD16 study (cHL: 36 years) and 42 years in the HD17 study (cHL: 31 years). The majority of NLPHL patients included in the HD16 and HD17 studies presented with a typical histopathological growth pattern (HD16: 66%; HD17: 70%) The 5-year PFS for all NLPHL patients was 90.3% (cHL: 90.8%) in the HD16 study and 92.9% (cHL: 95.7%) in the HD17 study. In the HD16 study, the 5-year PFS for the subgroup of PET-2-positive NLPHL patients was 89.3% (cHL: 91.6%); PET-2-negative NLPHL patients had a 5-year PFS of 91.0% (cHL: 90.4%). For PET-2-negative NLPHL patients assigned to the chemotherapy only arm, the 5-year PFS was 83.0% (cHL: 88.2%) whereas PET-2-negative NLPHL patients treated with chemotherapy plus RT had a 5-year PFS of 100% (cHL: 92.3%) (p=0.05). Subgroup analyses according to the PET-2 result were not conducted for NLPHL patients treated within the HD17 study due to the small number of individuals with NLPHL histology included in this trial. The 5-year OS for NLPHL patients treated within the HD16 and HD17 studies was 100% (cHL: 98.6% in HD16; 99.2% in HD17). Conclusion: Contemporary HL-directed treatment results in excellent 5-year outcomes for patients with newly diagnosed early-stage NLPHL and should thus be considered as valid approach for this patient group.

Treatment of Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Subgroup Analysis of the Randomized German Hodgkin Study Group HD16 Study

Background:Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for approximately 5% of all Hodgkin lymphoma (HL) cases. Pathological and clinical characteristics differ from classical HL (cHL). In contrast to cHL, the malignant cells in NLPHL are consistently positive for CD20 but stain negative for CD30. The clinical course of NLPHL is usually indolent and patients present with early-stage disease more frequently than in cHL.Patients and Methods:We investigated characteristics and outcomes of 85 patients with NLPHL (stage IB and stage II without risk factors) who had treatment within the randomized German Hodgkin Study Group HD16 study for early-stage HL. Results were compared to those from 495 cHL patients (stage IB and stage II without risk factors) treated within the same study. Patients were randomized between standard treatment consisting of 2 cycles of ABVD followed by consolidation radiotherapy and treatment guided by interim positron emission tomography after 2 cycles of ABVD (PET-2). PET-2-guided treatment consisted of 2 cycles of ABVD alone for patients with a negative PET-2 and 2 cycles of ABVD followed by consolidation radiotherapy for patients with a positive PET-2 (defined as a Deauville score ≥ 3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method including 95%-confidence intervals (95%-CI) and hazard ratios (HR) obtained from Cox regression models. Analyses were performed descriptively.Results:Overall, 62/85 NLPHL patients (73%) were male as compared to 254/495 cHL patients (51%) (p=0.0002). The median age was 37 years (range: 19-71 years) among patients with NLPHL and 36 years (range: 18-75 years) among patients with cHL (p=0.4380). Information on the histopathological growth pattern was available for 67/85 NLPHL patients of which 44 (66%) had a typical growth pattern. The PET-2 was positive in 39/85 NLPHL patients (46%) and in 171/495 cHL patients (35%) (p=0.0507). After a median observation time of 64 months, the 5-year PFS was 90.3% (95%-CI: 83.8-96.7%) for all 85 NLPHL patients and 90.8% (95%-CI: 88.1-93.5%) for all 495 cHL patients (HR=1.1; 95%-CI: 0.5-2.1). The 5-year PFS rates for PET-2-positive NLPHL (n=39) and cHL (n=171) patients were 89.3% (95%-CI: 79.4-99.2%) and 91.6% (95%-CI: 87.2-96%) (HR= 1.3; 95%-CI: 0.5-3.5), respectively. The 5-year PFS rates for PET-2-negative NLPHL (n=46) and cHL (n=324) patients were 91% (95%-CI: 82.7-99.4%) and 90.4% (95%-CI: 87-99.4%) (HR=0.85; 95%-CI: 0.3-2.4), respectively. PET-2-negative NLPHL (n=25) and cHL (n=152) patients treated with 2 cycles of ABVD alone had 5-year PFS rates of 83% (95%-CI: 67.8-98.2%) and 88.2% (95%-CI: 82.7-93.6%) (HR=1.5, 95%-CI: 0.5-4.5), respectively. In contrast, PET-2-negative NLPHL (n=21) and cHL (n=172) patients treated with 2 cycles of ABVD followed by consolidation radiotherapy had 5-year PFS rates of 100% and 92.3% (95%-CI: 88.1-96.5%) (HR=0; 95%-CI: 0), respectively. NLPHL patients with a typical growth pattern (n=44) had a 5-year PFS of 95.2% (95%-CI: 88.8-100%) whereas patients with an atypical growth pattern (n=23) had a 5-year PFS of 82.2% (95%-CI: 66.3-98%) (HR=2.5; 95%-CI: 0.5-11.2). A total of 9 NLPHL patients experienced disease progression or relapse during follow-up. The median time to NLPHL recurrence was 14 months (range: 1-89 months). There were 2 cases of second primary malignancies (1 case of malignant melanoma, 1 case of stomach cancer) among patients with NLPHL. No patient developed histological transformation into aggressive B-cell non-Hodgkin lymphoma. The 5-year OS rates were 100% and 98.6% (95%-CI: 97.5-99.7%) (HR=0; 95%-CI: 0) for patients with NLPHL and cHL, respectively.Conclusion:Taken together, the 5-year outcomes for patients with newly diagnosed early-stage NLPHL were similar to their counterparts with cHL. Thus, the current standard of care for early-stage cHL consisting of 2 cycles of ABVD followed by consolidation radiotherapy represents a highly active option also for the treatment of patients with the initial diagnosis of stage IB and stage II NLPHL without risk factors. DisclosuresFuchs: Takeda: Consultancy, Honoraria; Lukon: Honoraria; Celgene: Honoraria; BMS: Honoraria; MSD: Honoraria. von Tresckow: AstraZeneca: Honoraria, Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Pentixafarm: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Engert: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy; MSD: Honoraria; Hexal: Honoraria.

The stage-specific roles of radiotherapy and chemotherapy in nodular lymphocyte predominant Hodgkin lymphoma patients: a propensity score-matched analysis of the SEER database.

BackgroundThe stage‐specific roles of radiotherapy (RT) alone, chemotherapy alone, and combined RT and chemotherapy (CRT) for patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) have not been adequately evaluated.MethodsWe analyzed patients with all stages of NLPHL enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2015. Propensity score (PS) analysis with 1:1 matching (PSM) was performed to ensure the well‐balanced characteristics of the comparison groups. Kaplan–Meier and Cox proportional‐hazards models were used to evaluate the overall survival (OS), cancer‐specific survival (CSS), hazard ratios (HRs), and corresponding 95% confidence intervals (95% CI). Restricted mean survival times (RMST) were also used for the survival analyses.ResultsFor early‐stage patients, CRT was associated with the best survival, the mean OS was significantly improved by approximately 20 months (20 m), and the risk of death was reduced by more than 80%, both before and after PSM (p < 0.05). For advanced‐stage patients, none of RT alone, chemotherapy alone, or CRT had a significant effect on survival. Chemotherapy alone and CRT might be more beneficial for long‐term survival (RMST120 m: neither RT nor chemotherapy vs. chemotherapy alone vs. CRT = 104 m vs. 111 m vs. 108 m). Subgroup analysis of patients with early‐stage NLPHL showed that CRT was associated with better survival of elderly patients (improved OS = 43.8 m, HR = 0.14, p < 0.05). However, the survival benefits of treatments for young patients were not statistically significant. The efficacy of RT was significantly different between the age groups (p for interaction = 0.020).ConclusionsThese results from SEER data suggest that CRT may be considered for early‐stage NLPHL, especially for elderly patients. Further studies are needed to identify effective treatments in patients with advanced‐stage NLPHL.

Abstract PO-60: The stage-specific roles of radiotherapy and chemotherapy in nodular lymphocyte-predominant Hodgkin lymphoma patients: A propensity-matched analysis of the Surveillance, Epidemiology, and End Results database

Abstract Background: The stage-specific roles of radiotherapy (RT) alone, chemotherapy alone, and chemoradiotherapy (CRT) for patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have not been adequately evaluated. Methods: We analyzed patients with NLPHL in all stages enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2015. Propensity score (PS) analysis with 1:1 matching was performed to ensure well-balanced characteristics between the comparison groups. Kaplan-Meier and Cox proportional hazards models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), the hazard ratio (HR), and corresponding 95% confidence intervals (95% CI). Restricted mean survival times (RMST) were also used for the survival analyses. Results: For early-stage patients, RT alone was found to be associated with the improved survival of 10 months to 15 months and the deceased HR of 60% to 80%. Chemotherapy alone also had survival benefits (improved OS = 12.1 months; improved CSS = 5.3 months). However, not all of these improvements were statistically significant. CRT was associated with the best survival: the mean OS was significantly improved by 20 months and the HR was reduced by more than 80%, both before and after PS matching (PSM) (P &amp;lt; 0.05). For advanced-stage patients, none of RT alone, chemotherapy alone, and CRT had a significant effect on survival. Chemotherapy alone and CRT might be more beneficial for long-term survival (RMST120m: neither RT nor chemotherapy vs. chemotherapy alone vs. CRT = 104m vs. 111m vs. 108m). Subgroup analysis showed that the efficacy of RT alone in patients with early-stage NLPHL was significantly different between younger people and older people (age &amp;lt; 40: HR, 95% CI = 5.70, 0.34 - 94.2, P = 0.224; age ≧ 40: HR, 95% CI = 0.06, 0.01 - 0.32, P = 0.001; P for interaction = 0.005). Conclusions: The results from the large SEER database suggested that CRT was associated with the best survival of patients with the early-stage NLPHL. More effective treatment strategies for patients with advanced-stage NLPHL remain to be further studied. Citation Format: Shijie Wang, Mingfang Jia, Jianglong Han, Rui Zhang, Kejie Huang, Yunfeng Qiao, Ping Chen, Zhenming Fu. The stage-specific roles of radiotherapy and chemotherapy in nodular lymphocyte-predominant Hodgkin lymphoma patients: A propensity-matched analysis of the Surveillance, Epidemiology, and End Results database [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-60.

PB2000 OUTCOME OF PEDIATRIC NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA, IS ABVD THE BEST REGIMEN? 10 YEARS SINGLE CENTER EXPERIENCE, REPORT FROM CHILDREN CANCER HOSPITAL, EGYPT.

Background:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL) in children and accounts for 5–10% of all pediatric HL.Aims:The aim of the study to analyze the clinical characteristics and treatment outcome of Pediatric NLPHL.Methods:Retrospective study including all newly diagnosed patients less than 18 years old with NLPHL and treated in children cancer hospital Egypt CCHE between 2007 and 2017.Results:Among 43 pediatric NLPHL patients, 29 had early stage (18 with stage I, 11 with stage II). Fourteen patients had advanced stage (7 with stage III &amp; 7 with stage IV). Eleven patients had a mediastinal disease, 8 patients had splenic involvement, 2 patient had bulky disease and 10 patient had B symptoms at diagnosis.28 Patients with Early‐stage disease treatment; surgery and observation 6 patients, Chemotherapy 6 patients and Combined modality 17 patients. Relapse was seen in 7(25%) patients, 1 observation arm, 3 from chemotherapy arm (ABVD) and 3 from the combined arm (ABVD+IFRTH). 14 advanced stage patients received treatment; Chemotherapy (ABVD) 6 patients, Combined (ABVD+IFRTH) 8 patients, Relapse in 7 (50%) patients (all stage 4 disease), 6 from chemotherapy arm and 1 from the combined arm. 2 patients died (stage IV) from progressive disease and sepsis. B symptoms, mediastinal and splenic involvement had a significant impact on DFS on univariate analysis while combined treatment modality (Chemotherapy and Radiotherapy) had an impact on the outcome of both univariate and multivariate analysis.5 Years DFS, OS for whole group was 64% and 94% respectively, while 5y DFS for early stage 83% and advanced stage 45% (p‐value = .01) and 5 Years OS for early stage was 100% and advanced stage 87 % (p‐value = .08).Summary/Conclusion:Early stage NLPHL had a better outcome but unexpected higher relapse in chemotherapy treatment arm raising a question about the role of radiotherapy while advanced stage disease had poor outcome rising a question of what should be the best chemotherapy regimen for pediatric NLPHL patients.

Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall survival rates exceeding 90% after involved-field radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than stage IA). In contrast, patients with advanced disease at diagnosis tend to relapse either with NLPHL histology or with histological transformation into aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL patients with multiple relapses successfully respond to salvage therapy in many cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to high-dose chemotherapy followed by autologous stem cell transplantation. Treatment at disease recurrence should be chosen on the basis of various factors, including histology at relapse, time to relapse, extent of disease at relapse, and prior treatment. Because death among NLPHL patients is more often caused by therapy-related late effects than lymphoma-related complications, optimizing the risk-benefit ratio of treatment by decreasing toxicity whenever possible is the major goal of clinical research in this disease.

A 20-year population-based study on the epidemiology, clinical features, treatment, and outcome of nodular lymphocyte predominant Hodgkin lymphoma.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4–257 months). Median age at diagnosis was 43 years (range 1–87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21–74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome.

Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: The Impact of Radiation Therapy on Overall Survival

Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: The Impact of Radiation Therapy on Overall Survival

Race-specific features and outcomes of nodular lymphocyte-predominant Hodgkin lymphoma: Analysis of the National Cancer Data Base.

The incidence of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is higher among African Americans than among other races, but to the authors' knowledge, the characteristics of NLPHL in this population have not been evaluated. The authors compared clinical features, treatments, and survival of black and white patients with NLPHL using the National Cancer Data Base. The authors extracted the records of 602 black and 1950 white patients with NLPHL who were diagnosed between 1998 and 2011. Overall survival (OS) was compared using the log-rank test. Black patients were on average younger than white patients (median age, 42 years vs 45 years; P =.0001), more often female (49% vs 29%; P<.0001), and more likely to have the axillary lymph nodes as the primary disease site (25% vs 17%; P =.0002). They also had unfavorable socioeconomic characteristics, a higher rate of no treatment in patients with early-stage disease, and a longer time to therapy initiation (median, 53.5 days vs 47 days; P<.0001). Despite this, the authors found no significant difference between the races with regard to stage distribution or survival (P =.39). OS at 7 years was 90.1% in patients with early-stage (American Joint Committee on Cancer stage IA/B, IIA) and 79.4% in patients with advanced stage (American Joint Committee on Cancer stage IIB, III/IV) NLPHL. Survival in the early stage of disease was not found to be significantly different after various treatment strategies (stratified log-rank P = .18), except that the administration of chemotherapy was associated with a better outcome in black patients (log-rank P =.011 vs P =.81 for white patients). Differences in clinical presentation suggest the interaction of race-specific and sex-specific susceptibility factors for NLPHL. Further research is needed to elucidate these factors, and to investigate possible heterogeneous effects of treatments by race. Clinical trials comparing standard treatment strategies are unlikely to detect differences in OS among patients with early-stage NLPHL.

Nodular lymphocyte-predominant Hodgkin's lymphoma: Principles of diagnosis and treatment

To describe the clinical and morphological features of the rare Hodgkin's lymphoma (HL) subtype--nodular lymphocyte-predominant HL (NLPHL). Forty-two patients were diagnosed with NLPHL in 2010 to 2014. The male to female ratio was 2.2:1; the median age was 37 years (range 17-68 years). NLPHL was diagnosed on the basis of the histological and immunohistochemical examinations of tumor biopsy specimens; disease stages were determined by standard HL studies. Before NLPHL was detected, 23 (55%) patients were diagnosed as having HL in 13 cases, follicular lymphoma in 2, lymphofollicular hyperplasia in 3, angioimmunoblastic lymphoma in 1, diffuse large B-cell lymphoma in 3, and B-cell lymphoma (non-HL) in 1. Long-term (3-21-year; median 8 years) persistent lymphadenopathy was observed in 16 (38%) patients. Seventeen (40.5%) patients had early (I-II) stages of the disease and 25 (59.5%) had advanced stages. B symptoms were noted in 24% of cases. There was involvement of extranodal sites (salivary gland, tonsil) in 2 patients, spleen in 14 (33%), bone marrow in 8, and bulky disease in 2. Cycles of ABVD ± rituximab ± radiotherapy (RT) were used in early-stage NLPHL; those of R-BEACOPP-14 ± RT were performed in the advanced stages of the disease or its transformation to diffuse large B-cell lymphoma with excessive T cells. When patients have a history of long-term asymptomatic lymphadenopathy, it is necessary to rule out NLPHL, for which purpose an immunohistochemical examination of a biopsy specimen and its reexamination in a laboratory having experience in diagnosing NLPHL must necessarily be done. Lower RT doses and rituximab incorporated into the cycle of treatment are indicated to reduce its toxicity and to preserve therapeutic efficiency.

Race-Specific Features and Treatment Patterns of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) in the United States: Analysis of the National Cancer Data Base

Background: NLPHL is a rare, biologically distinct subtype of Hodgkin lymphoma (HL) characterized by late recurrences and risk of transformation to non-Hodgkin histology. The incidence of NLPHL is markedly increased among black patients (pts), but they were not distinguished in prior studies, and data are lacking about specific features in this group. Relative benefits of various treatment modalities in early-stage NLPHL are also controversial. Radiation therapy (RT) is endorsed by guidelines, but one large study suggested a survival advantage of combined modality therapy (CMT) over historical controls treated with RT alone (Savage et al., Blood 2011:118:4585). The objective of this study was to compare clinical features of NLPHL in black and other pts, and to describe treatment patterns and survival using the National Cancer Data Base a registry capturing over 70% of incident cancers in the United States (US).Methods: We identified NLPHL and classical HL cases diagnosed between 1998 and 2011, with survival data available for the 1998-2006 cohort. Receipt of chemotherapy (ChT), RT or CMT as initial course of treatment was recorded. Stage was categorized as limited (Ann Arbor I, IIA) or advanced (IIB, III, IV). Overall survival (OS) was the primary outcome and was compared using log-rank tests stratified by stage, sex and age group. Trends were assessed using log-linear regression. All confidence intervals (CI) were set at 95%.Results: Among the NLPHL pts (N=2,656), 23% were of black race (N=602), compared with 10% of classical HL cases (N=66,369). Most NLPHL pts presented with limited stage disease (66%), without any difference between races (P=0.79). Stage migration was evident between 1998 and 2003 with the proportion of stage III/IV cases increasing by 13.2% per year (CI, 3.3-24.0, P=0.008). The male-to-female ratio was 1.0 (CI, 0.9-1.2) in black pts, whereas pronounced male predominance was present in others (ratio 2.5, CI, 2.2-2.7). Black pts were also on average younger (median age 42 years, versus 45 for others, P=0.0001), and their NLPHL more often originated from the axillary nodes (25%, versus 17% for other races, P=0.0003).Median follow-up was 7.1 years. OS at 7 years was 90.1% (CI, 87.7-92.1) for limited- and 80.1% (CI, 75.6-83.8) for advanced-stage NLPHL, with no difference between the races (P=0.15, Fig. A). In limited disease, RT alone was used in 55%, 31% and 27% of pts with stage IA, IB and IIA, respectively, while CMT was used in 21%, 33% and 35%, and ChT alone in 12%, 24% and 31%, respectively. Black pts were more likely to have no treatment recorded (P<0.0001), but the proportions of various modalities was otherwise the same (P=0.76). The difference in OS between the treatments was not significant, with 7-year OS of 93.3% (CI, 88.8-96.1) after CMT, 90.0% (CI, 85.7-92.9) after RT, and 86.5% (CI, 79.5-91.2) after ChT alone (P=0.12, Fig. B). There was a significant trend towards decreased utilization of RT over time (on average by 1.6% per year, P=0.0002).In advanced NLPHL, 71% of patients were treated with ChT alone, 15% with CMT, 3% with RT alone and 11% had no recorded treatment. A significant trend towards less RT was again evident (8.9% per year, P<0.0001).Conclusions: The specific gender, age and primary site distribution in black pts with NLPHL suggests an inherited susceptibility, possibly mediated by immune or endocrine factors. Survival outcomes are not different from other races. In early-stage NLPHL, various treatment modalities are not associated with significant OS differences, although survival is numerically highest with CMT. Because of stage migration coinciding with the introduction of positron emission tomography, stage-based survival comparisons with cohorts from 1990’s may be biased. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treatment of Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): An Analysis from the German Hodgkin Study Group (GHSG)

Introduction: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for about 5% of all HL cases. As compared with classical HL (cHL), NLPHL is characterized by the absence of CD30 and the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. Given a more indolent clinical course, especially early-stage NLPHL is often treated less aggressive than classical HL (cHL). In stage IA patients, radiotherapy (RT) alone is applied at most institutions. However, this clinical practice is not based on data from prospective clinical trials with sufficient follow-up. To shed more light on the optimal treatment of stage IA NLPHL, we performed an analysis including patients with long-term follow-up treated within German Hodgkin Study Group (GHSG) clinical trials.Patients: A total of 256 stage IA NLPHL patients treated within 7 prospective GHSG studies between 1988 and 2009 were included in the analysis. Treatment consisted of combined-modality treatment (CMT) (n=72), extended-field RT (EF-RT) (n=49), involved-field RT (IF-RT) (n=108) or four weekly doses of the anti-CD20 antibody rituximab (n=27).Results: The median age at NLPHL diagnosis was 38.5 years (range: 17-75); 194/256 (75.8%) patients were male and 62/256 (24.2%) patients were female. Median follow-up for the whole patient group was 91 months (98 months for CMT, 118 months for EF-RT, 87 months for IF-RT, 49 months for rituximab). All patients responded to treatment irrespective of the treatment modality applied. At 8 years, progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 94.5% for CMT, 84.3% and 95.7% for EF-RT and 91.9% and 99.0% for IF-RT; 4-year PFS and OS rates for patients treated with rituximab were 81.0% and 100%. Seventeen patients developed a second malignancy in the course of follow-up (8 after CMT, 3 after EF-RT, 4 after IF-RT, 2 after rituxmab). Nine of these second malignancies were solid tumors (4 after CMT, 2 after EF-RT, 1 after IF-RT, 2 after rituximab) and 8 were hematologic malignancies (4 after CMT, 1 after EF-RT, 3 after IF-RT, none after rituximab). A total 12 deaths occurred. The most common cause of death was cardiac failure (n=3). Only one patient died from NLPHL.Conclusion: Based on this large analysis with long-term follow-up, IF-RT should be the standard of care for stage IA NLPHL. Treatment with single agent rituximab is associated with an increased event rate when compared with IF-RT and should therefore not be routinely used in stage IA NLPHL patients. However, given the shorter follow-up in comparison with CMT, EF-RT and IF-RT, final conclusions regarding rituximab especially in terms of treatment-related late sequelae cannot yet be drawn. Addition of chemotherapy does not improve the excellent outcome achieved with RT alone. DisclosuresOff Label Use: Rituximab in NLPHL.

Long-Term Outcomes in Patients with Early Stage Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma Treated with Radiotherapy

PurposeRadiation therapy (RT) is commonly used as definitive treatment for early-stage nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL). We evaluated the cause-specific survival (CSS), overall survival (OS), and second malignancy (SM) rates in patients with early-stage NLPHL treated with RT.Methods and MaterialsPatients with stage I-II NLPHL between 1988 and 2009 who underwent RT were selected from the Surveillance, Epidemiology and End Results database. Univariate analysis (UVA) for CSS and Os was performed using the Kaplan-Meier method and included age, gender, involved site, year of diagnosis, presence of B-symptoms, and extranodal involvement (ENI). Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling and included the above clinical variables. SM were classified as RT-related or non-RT-related. Freedom from SM and freedom from RT-related SM were determined using the Kaplan-Meier method.ResultsThe study cohort included 469 patients. Median age was 37 years. The most common involved sites were the head and neck (36%), axilla/arm (26%), and multiple lymph node regions (18%). Sixty-eight percent had stage I disease, 70% were male, 4% had ENI, and 7% had B-symptoms. Median follow-up was 6 years. Ten-year CSS and Os were 98% and 88%, respectively. On UVA, none of the covariates was associated with CSS. Increasing age (p<0.01) and female gender (p<0.01) were associated with worse Os. On MVA, older age (p<0.01), female gender (p=0.04), multiple regions of involvement (p=0.03), stage I disease (p=0.02), and presence of B-symptoms (p=0.02) were associated with worse Os. Ten-year freedom from SM and freedom from RT-related SM were 89% and 99%, respectively.ConclusionsThis is the largest series to evaluate the outcomes of stage I-II NLPHL patients treated with RT and found that this patient population has an excellent long-term prognosis and a low rate of RT-related second malignancies.

Phase II Study of Rituximab in Newly Diagnosed Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Report From the German Hodgkin Study Group (GHSG)

Abstract 2711 Background:Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) accounting for about 5% of cases. The clinical course is usually more indolent than in classical HL (cHL) resulting in an excellent long-term prognosis. This is particularly true for patients diagnosed with early-stage NLPHL representing the majority of cases. However, current standard treatment consisting of chemotherapy and/or radiotherapy (RT) is associated with an increased risk of late toxicity. Thus, there is a need for novel treatment strategies. Since CD20 is consistently expressed on the malignant lymphocyte-predominant (LP) cells, anti-CD20 antibody treatment appears to be a promising option. After impressive response rates were reported in relapsed NLPHL patients, the German Hodgkin Study Group (GHSG) initiated a trial to evaluate the anti-CD20 antibody rituximab in newly diagnosed stage IA NLPHL without clinical risk factors. Methods:Between June 2006 and October 2007, 29 patients from 23 sites were enrolled in this multicenter phase II trial. Study entry was restricted to adult patients (age 18 to 75) with biopsy-proven stage IA NLPHL without clinical risk factors. Treatment consisted of four weekly infusions of the anti-CD20 antibody rituximab at a dose of 375 mg/m2. Efficacy endpoints included remission status as assessed by computed tomography (CT) four weeks after completion of treatment, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) at two years; feasibility endpoints were acute treatment-related toxicities, adverse events, dose reductions and therapy delays. Results:Twenty-eight patients were eligible for the final analysis of this phase II trial; 71.4% of patients were male, 72% had supradiaphragmatic disease and the median age was 40 years. Treatment was conducted in the outpatient setting in the majority of cases. Rituximab was well tolerated; no grade III/IV toxicities were observed. Transfusions of erythrocytes or platelets were not required. At final restaging four weeks after the last rituximab application, 24 patients (85.7%) were in CR/CRu and four patients (14.3%) had partial remission (PR). Thus, overall response rate (ORR) was 100%. After a median follow-up of 43 months, all patients were still alive. Progression-free survival rate estimates at two, three and four years were 85.3%, 81.4% and 77.1%, respectively. Seven patients (25%) have relapsed and two patients developed secondary solid tumors. All patients with NLPHL relapse were successfully salvaged. Conclusions:The results of the present trial confirm the previously reported excellent response of NLPHL patients to rituximab. However, with a relapse rate of 25% at a median observation time of 43 months, rituximab does not seem to be as effective as RT alone or combined-modality strategies in stage IA NLPHL patients. Nonetheless, anti-CD20 antibodies have a favorable toxicity profile and may be offered to selected patients who are at particular risk for long-term side effects such as secondary malignancies. In addition, the combination of anti-CD20 antibodies and chemotherapy may also improve efficacy and decrease toxicity of NLPHL treatment in early unfavorable, advanced or relapsed disease. Disclosures:No relevant conflicts of interest to declare.

Treatment of Children & Adolescents with Early Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma with a Low Intensity Short Duration Chemotherapy Regimen [CVP] - on Behalf of the EuroNet-PHL Group.

Background: Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) is a distinct clinicopathologic subtype of Hodgkin's lymphoma [HL]. Reports in published literature suggest that very little, and occasionally, no chemotherapy is sufficient for long term survival in patients with LPHL and that this disease appears to have a more indolent course than classical HL. The optimum therapy for early stage NLPHL is not known, but it is likely that current therapy for classical Hodgkin's lymphoma is unnecessarily toxic and intensive for this indolent, slowly progressive, CD 20 positive disease. Adverse treatment related late effects are the major causes of morbidity and death. Consequently children with early stage NLPHL represent ideal candidates for low intensity treatment.Study Objectives: To assess whether a non-intensive chemotherapy regimen consisting of cyclophosphamide [500mg/m2 iv- day 1], vinblastine [6 mg/m2 iv-day1 & 8] and oral prednisolone [40 mg/m2 - days 1–7] (CVP) every 14–21 days, count dependent, could replace standard chemotherapy protocols used for classical HL without compromising efficacy in children and young people with NLPHL.Patients and Methods: Between May 2004 and April 2006 18 patients with stages IA [n=12] and IIA [n=6] biopsy proven NLPHL were treated with 3 cycles of CVP chemotherapy. Three of the eighteen patients were initially treated with surgical resection alone and received CVP at first relapse. Ten patients were males and the median age at diagnosis was 10 years (range 7–15 years). Staging investigations at diagnosis included both conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Remission status at the end of 3 cycles of CVP was confirmed by both conventional cross sectional and PET imaging.Results: 17 patients achieved a complete remission [CR] after 3 courses of CVP and 1 patient a very good partial remission [VGPR]. To date, only 1 patient has relapsed while all the remaining patients remain in continuous CR. Median duration of follow up is 12 months (range 2–26 months). The overall survival is 100% and event free survival is 94%. No significant early or late toxicity has been observed to date.Conclusions: Nothithstanding the relatively short follow up period, CVP is an effective non toxic chemotherapy regimen with 95% of patients with early stage NLPHL achieving a CR after 3 courses. Based on these preliminary results, we have designed a prospective European study for patients with stage IA & IIA NLPHL to confirm these results in a larger cohort of patients.