Key points: - Accurate staging and risk stratification are required for treatment decision‐making. The stage according to the Ann Arbor classification is determined by baseline positron emission tomography (PET) and contrast‐enhanced computed tomography (CT) (PET/CT). - Given its higher sensitivity, PET/CT has superseded the requirement for a bone marrow biopsy at diagnosis. - Pretreatment clinical risk factors as defined by different study groups divide early‐stage patients into an early‐stage favorable and an early‐stage unfavorable group. In Stage IIB patients, the presence of certain risk factors can result in the allocation to the advanced‐stage group (See Table 1 in original paper). - Standard treatment for early‐stage favorable classic Hodgkin lymphoma (cHL) consists of two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), followed by 20 Gy involved‐site radiotherapy (IS‐RT) (recommendation level 1 grade A [1A]). See Figure 1 in original paper. - Two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) (1A) or a procarbazine‐free eBEACOPP variant (4A) plus two cycles of ABVD (“2+2”), followed by 30 Gy IS‐RT in the case of PET/CT positivity and no further treatment in the case of PET/CT negativity after chemotherapy should be considered in patients with early‐stage unfavorable cHL ≤ 60 years. - If a less intensive approach is preferred and in individuals > 60 years, four cycles of A(B)VD followed by 30 Gy IS‐RT can be given (1A). - In patients aged > 60 years, the use of bleomycin should be restricted to no more than two treatment cycles; omission of bleomycin should be considered in patients aged > 70 years (3A). - In advanced classic HL (stage III/IV and stage IIB presenting with large mediastinal mass and/or extranodal manifestations) are usually treated with systemic therapy alone. IS-RT is confined to cases with PET/CT‐positive residual disease at the end of systemic therapy. Brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) for four (in the case of PET/CT negativity after two cycles) or six cycles (in the case of PET/CT positivity after two cycles), followed by PET/CT‐guided 30Gy IS‐RT should be considered in patients ≤ 60 years (1A). See Figure 2 in original paper. - Six cycles of the anti-PD-1 antibody nivolumab and AVD (N‐AVD) followed by PET/CT‐guided 30 Gy IS‐RT represents a less intensive alternative for younger patients and the preferred approach for patients > 60 years. ● The authors of this guideline cite the SWOG S1826 randomized trial, which included patients aged 12 to 84 years and demonstrated the superiority, in terms of progression-free survival, of the N-AVD combination compared with brentuximab vedotin in combination with AVD (BV-AVD). However, they clarify that longer follow-up may be necessary to draw definitive conclusions. - In older patients with advanced classic HL, two cycles of A(B)VD followed by four cycles of AVD represents an alternative to approaches including targeted agents (3A). - In older patients with advanced classic HL who are not eligible for multiagent chemotherapy, possible approaches include combinations of BV with a PD‐1 inhibitor or dacarbazine or single‐agent conventional chemotherapy (3B). - A biopsy to confirm the progression or relapse should be obtained whenever possible (3A). - High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) represents the standard approach for most patients with refractory and relapsed cHL who are eligible for this approach (2A). - In countries in which PD‐1 inhibitors are available and reimbursed, salvage treatment before HDCT and ASCT should consist of a PD‐1 inhibitor combined with chemotherapy either concomitantly or sequentially if response to the PD‐1 inhibitor given as a single agent is insufficient (3B). - For BV‐naive patients in countries in which BV but no PD‐1 inhibitors are available and reimbursed or in patients not eligible for treatment with PD‐1 inhibitors, BV in combination with chemotherapy is recommended as salvage treatment before HDCT and ASCT (2A). - RT to PET‐positive sites should be considered prior to or following ASCT (3A). - BV maintenance following ASCT is recommended for high‐risk patients (1A). - The treatment strategy for patients with relapse after HDCT and ASCT should be chosen individually and adapted to the previous treatment (3A). ● Allogenic stem cell transplantation (AlloSCT) should be discussed with all eligible patients responding to treatment, for example, PD‐1 inhibitors, taking into account individual risks and potential benefits (3B). ● AlloSCT should be discussed with all fit patients who are refractory to or who progress on or after PD‐1 inhibitor therapy (3A). - PD‐1 inhibitors given as a single agent represent the preferred treatment for patients with refractory or relapsed cHL not eligible for HDCT and ASCT (2A). - If patients are not eligible for PD‐1 inhibitors or treatment with PD‐1 inhibitors is not reimbursed, single‐agent BV for up to 16 cycles is recommended, especially in individuals who are BV naive (2A). - In patients with localized relapse, RT alone or together with a PD‐1 inhibitor can be considered (3A). - Patients with stage IA NLPHL without clinical risk factors should be treated with 30 Gy IS-RT alone (2A). - In early stages other than stage IA without clinical risk factors, approaches also used in classic HL optionally combined with an anti CD20 antibody should be considered as available data indicate very good outcomes (2A). - In advanced NLPHL, the management strategy for the individual patient should be chosen based on factors such as age, lymphoma burden, affected sites, and systemic symptoms; it can range from active surveillance to intensive chemotherapy in combination with an anti‐CD20 antibody (4B). - In histologically confirmed NLPHL recurrence, treatment should be chosen individually based on factors such as age, previous treatment, and stage at relapse. Treatment options range from single‐agent anti‐CD20 antibody treatment to HDCT and ASCT (4B). - BV and PD‐1 inhibitors should not be used in NLPHL (5A). |
