Intermediate-Risk Lymphocyte-Predominant Hodgkin Lymphoma: AHOD0031: A Report from the Children's Oncology Group

Abstract

Background: Children's Oncology Group (COG) AHOD0031 demonstrated that early response assessment in pediatric intermediate-risk Hodgkin lymphoma (HL) permits reduction or augmentation in therapy with maintenance of excellent event-free (EFS) and overall survival (OS). While the majority of patients on this trial had classical HL (cHL), patients with lymphocyte-predominant HL (LPHL) were included. Pediatric patients with LPHL typically present with localized disease and such low risk patients have excellent outcomes with surgical resection alone or minimal chemotherapy. However, management of patients with intermediate-risk LPHL is less clear due to their small number in most clinical trials. We report the outcomes of these patients on AHOD0031 and present directions for future therapeutic strategies.Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. Patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), followed by a response evaluation of rapid early (RER) versus slow early responder (SER) status. All SER patients were randomized to an additional two cycles of ABVE-PC +/- 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA). All SER patients received 21 Gy involved field radiotherapy (IFRT) following completion of chemotherapy. RER patients received 2 additional cycles of ABVE-PC. RER with complete responder (CR) status (RER/CR) patients were randomized to involved field radiotherapy (IFRT) or no further therapy. RER/non-CR patients were non-randomly assigned to IFRT.Results: Ninety-seven (5.7%) of the 1712 eligible patients on AHOD0031 had LPHL, with the remainder cHL. Compared to patients with cHL, patients with LPHL were younger (p=0.0001), more often male (p<0.0001), and less likely to have B symptoms (p=0.0006), bulk (p<0.0001) or stage IV disease (p<0.0001). Five-year event-free survival (EFS) was marginally superior in patients with LPHL (91.2%) compared with cHL (83.2%) (p = 0.08) (Figure 1), without difference in overall survival (OS) (p = 0.21). LPHL patients treated with chemotherapy alone (N = 33) had a 5-year EFS of 93.4% and OS of 100%. Stage and presence of bulk disease, RER or SER status and use of IFRT did not impact EFS or OS in LPHL patients. The proportion of patients who were RER was higher in LPHL compared with cHL (93.7% vs. 81.0%). Furthermore, LPHL patients were more likely to achieve a CR compared to cHL patients (68% vs. 45%; p=0.00003). There was only one reported subsequent malignant neoplasm among the LPHL patients, a non-Hodgkin lymphoma one year after treatment in a patient who received IFRT.Discussion: Children and adolescents with intermediate-risk LPHL represent ideal candidates for response-adapted therapy based on their favorable outcomes as demonstrated in this analysis. The majority of patients treated with the ABVE-PC backbone achieve RER/CR status and can be successfully treated without radiation therapy. Future therapeutic strategies should focus on further reduction in cytotoxic therapy for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.