How I treat advanced Hodgkin lymphoma — a global view (2020)

We haematologists always seek to follow standardized guidelines of practice and apply the best treatment for our patients with blood diseases within our means. However, treatment can never follow an exact recipe. Opinions differ as to the best approach, sometimes more than one treatment approach results in identical outcomes, or treatments differ only by the manner in which they fail. Furthermore, the haematologist is faced with constraints relating to the local economic environment. Patients too are not the same the world over. Early presentation is commoner in the developed world, as is the patient's understanding of the disease process. This in turn impacts the way patients are managed, the rigorousness of patient adhesion to the treatment schedule and the outcome. For these reasons, given the same starting conditions, patients will be treated differently according to the institute and the country they are in. In this series of global views, we have tasked experts from around the world to describe their management plan and rationale for a specific disease presentation. Here we explore the management of Hodgkin lymphoma (HL) at six different institutes worldwide. We finish with a conclusion from a lymphoma expert comparing and contrasting these different management styles, weighing in on their merits and limitations. The case history and questions posed to the experts are shown in Box 1 and their responses are summarized in Table I. PET scan, PFTs with DLCO (if using bleomycin) and echo (and fertility preservation); no bone marrow, unless for patients over age of 60–65 years and with cytopenias Younger pts ages < 60–65 years: A + AVD for IPS 3-7; RATHL based therapy for IPS 0–2 pts ages> 60–65 years who are fit: sequential BV and AVD; for unfit: brentuximab vedotin ± DTIC Transplant-eligible: ICE if relapse < 1 year vs. Brentuximab vedotin if relapse> 1 year followed by ASCT; BV maintenance after transplant if> 2 risk factors Transplant-ineligible: BV ± PD1 inhibitor (unless resistant to the former- then PD1 inhibitor alone) PET-adapted. ABVD. escBEACOPP is used by some centres for high-risk patients PET2 response: For PET- patients (DS1–3) then AVD × 4 For PET+ patients (DS 4 or 5) some centres in UK escalate to escBEACOPP. Alternatively ifosfamide-containing salvage for DS5 patients followed by ASCT in those patients who respond Re-biopsy Ifosfamide-containing salvage followed by ASCT for patients who are PET− (DS 1–3) after salvage For PET+ patients after 2 cycles of salvage, second-line salvage – BV ABVD is the regimen of choice. DS 5 patients on PET2 are escalated to IGEV. DS 4 patients generally continue on ABVD The preferred salvage at Barts is IGEV Histological diagnosis, preferably on excisional biopsy Assessment of disease extent and risk factors by PET Discuss measures to preserve fertility Consider in-patient administration of the first escBEACOPP cycle Laboratory safety assessments 2-3×/week. Dose delay and/or reduction in case of prolonged haematologic recovery Consolidative RT with 30 Gy to PET+ (DS ≥ 3) residues. Regular follow-up visits at increasing intervals for the first 5 years. Focused on treatment-related toxicities and cancer-related fatigue Open biopsy wherever feasible, otherwise a trucut biopsy adequate for histopathology and immunohistochemistry Staging with resource constraints: clinical examination, ultrasound abdomen, chest X-ray and bone marrow biopsy Staging – No resource constraints: whole body PET/CT scan Resource constraints: ABVD 6 cycles regardless of stage No resource constraints: ABVD × 6 with plan for interim PET2 Resource constraints: Interim assessment with clinical examination, ultrasound and chest X-ray, depending on site of initial disease No resource constraints: Omit further bleomycin if interim PET2− Resource constraints: IFRT to sites of initial bulk disease Clinical follow-up every 3 months No resource constraints: IFRT to sites of initial bulk disease or PET + lesions> 1·5 cm Clinical follow-up every 3 months CT-guided biopsy of the mediastinal mass A 21-year-old male has been feeling more and more fatigued over the last four weeks. During the last two, he has been experiencing night sweats and shortness of breath. His girlfriend has found swellings on his neck. A visit to his GP resulted in blood sampling, which showed anaemia and decreased albumin levels. A chest X-ray revealed pronounced mediastinal gland swelling and a diffuse parenchymatous affection. The patient is referred to a secondary centre for evaluation on the suspicion of advanced cancer. We hope that this exercise brings home to practising clinicians that there is more than one “right” way to manage patients. There are always things to learn from the way other experts practice. Moreover, there is much to learn from our colleagues working in strained economies. That teaches us that we should be nuanced in our perception of how and why treatments differ worldwide. The constellation of fatigue, fevers, night sweats and anaemia associated with mediastinal lymphadenopathy in a younger patient is concerning for a potential lymphoid malignancy. We would assess for weight loss >10% in the last six months, drenching night sweats, high fevers and pruritus. A thorough physical exam should evaluate for palpable lymphadenopathy, evidence of hepatosplenomegaly, and for extra-nodal involvement. If a palpable node is identified, this may be considered for excisional lymph node biopsy. If not, computed tomography (CT) imaging of the chest with contrast (+/− for disease would be excisional lymph node biopsy is the preferred of choice. a biopsy may be considered if the excisional biopsy is not to of the of has been further evaluation should be as blood and for and This should be followed by whole body tomography for disease 2 bone marrow biopsy a of with of the can marrow with a and of In of and potential bleomycin a and should be fertility with of should be to this given the potential of with a of with disease in the and the disease is as Furthermore, his is male stage × and albumin ABVD has been a treatment in for with an and and of and for patients years of therapy is an that has shown and and or in have been the in Hodgkin and treated patients with initial cycles of ABVD. In PET2 patients of to four more cycles of ABVD vs. AVD Patients with (DS 4 or 5) their treatment to or escalated In of patients PET2− The in the ABVD vs. in the AVD which for In the PET2 + the in an with follow-up of the for patients with PET2 disease only approach is based from the which patients to ABVD brentuximab vedotin + for to six This not a approach, PET2 scan cycle 2 of treatment and patients with a DS of 5 to an The of A + AVD resulted in a of with in the ABVD specific of those with ≥ 1 extra-nodal IPS ≥ stage age than years and male to more with A + AVD to patients treated in with A + AVD with an of over ABVD. given the patients younger age and disease stage and high we would A + AVD therapy for this is to that a with A + AVD for is to and there should be evaluation for the PET may be after or cycles of A + AVD For PET2 generally four cycles of therapy are For those with PET2 + disease DS A + AVD may be to an regimen of the is not For patients with disease with a PET + therapy may be considered based in on the However, is not if these may be to In patients with a scan at the of therapy with suspicion for or biopsy should be to of salvage There should be of on and clinical with in to months may be In those with a interim and/or patients may a and This may every six months for to months the There should be visits and for blood every months this imaging is of patients will have or depending on the therapy is our to relapse with biopsy. For patients with disease is with salvage therapy followed by an transplant The are in patients with those with relapse of as and extra-nodal A of salvage are in ICE and as as brentuximab vedotin or BV The of salvage therapy should be of disease to BV in with inhibitor therapy has been as and in patients with high-risk disease as relapse months after therapy or relapse months after therapy with extra-nodal we maintenance therapy with BV based on the patients who BV a of and those with at risk factors with For patients who are or after an inhibitor is with an In the would be practice for this patient to be referred a local on the the patient has been in the our approach is to an ultrasound scan of the with a if the lymph node on of an lymph biopsy is an biopsy the in with other are using to the process. evaluation blood bone and for the of lymphoma has been patients are by tomography We have from bone marrow on patients with disease that is generally that PET/CT can bone marrow We would then be in our and a treatment plan would be treatment in the UK for Hodgkin lymphoma (HL) ABVD or escalated and our we patients with six cycles of of centres in the UK have the practice of escalated for the high-risk patients. is more evidence for in A of have the of patients treated with ABVD The six cycles of four escalated cycles of and six cycles of and bleomycin) in patients with advanced patients who no ABVD vs. vs. disease this by the risk of secondary in the risk at years vs. for ABVD and In the patients with and to six cycles of ABVD or in cycles of the escalated regimen followed by four the from in the vs. this not a This patients who initial ABVD be with salvage with to those who that patients can be with over a However, are with with an of haematologic and This in the patients with high-risk stage to cycles of ABVD 4 + and the vs. and for ABVD and for a of the and with the a we have to patients with with six cycles of ABVD. of the RATHL centres in the UK have a patients a cycles of ABVD followed by an interim PET/CT Patients with a scan as DS 1–3) with a further four cycles of ABVD of bleomycin For patients with a scan (DS treatment escalated to In patients a interim to the ABVD and to ABVD and AVD showed with a of in the ABVD and in the AVD Patients who with bleomycin more 3 or 4 the of this we patients to AVD on the of a PET scan after cycles of ABVD. the RATHL patients a interim PET and after to the The a approach patients who PET + after cycles of ABVD escalated to with a of for this patient Furthermore, PET2 + patients treated on the followed the same approach with a of In this patients PET2 + and the as DS Patients with DS 5 of the different these PET2 + In patients with DS of 4 vs. the vs. < and the vs. < This treatment are for this high-risk of patients. The a different Patients who PET + an interim PET after cycles of ABVD escalated to an ifosfamide-containing salvage treatment followed by PET as DS 3 or of the patients PET2 + and the salvage regimen with on ABVD as by the of in the PET2 + and to those patients who PET2− PET2 + vs. For those patients who have DS 5 on an interim PET after cycles of we would plan to a biopsy and with an ifosfamide-containing salvage regimen followed by transplant on the of the for this patient if treatment is escalated to For those patients with a DS 4 on we have generally with ABVD on the of a more of we an of treatment PET scan six after the last of For those patients who have not a we plan for a biopsy. If is the patient is treated with an ifosfamide-containing salvage treatment is our regimen of by an There is a of patients is and this is on a case by case For those patients who have a clinical follow-up every months in the first in are only on the of clinical of is to the of by a biopsy to the of a in or as the of treatment at this in a would be to a PET which is then with an This approach will be in of patients. There are salvage with to in However, these are with no of one over our we IGEV and a of there are no to the of cycles of salvage our the patient would cycles of salvage and then be by If PET− (DS 1–3) cycle the patient would a further cycle of IGEV followed by The patient would then to a and This is based on from which the in from treatment not of ASCT over The that with BV ASCT in high-risk patients However, this approach is not in the For those patients who not a PET a second-line salvage therapy is given of the associated with disease that In this BV is used and has been shown to as a to ASCT in of The PD1 and are not to in the UK in this The of this patient is for patients with a age of around 30 years at first diagnosis, is one of the in patients with and and/or of patients from as night sweats and weight may extra-nodal sites the and bone suspicion of a the is to be on the biopsy of a lymph node or of The biopsy should an lymph if or a of are of as they not the of the lymph node and an If the of is the of the disease stage and risk is for the of initial for an clinical computed tomography of and and a bone marrow biopsy unless bone marrow can be by If PET- is for initial the of patients should measures fertility with a patients should be the of is a in However, the of the treatment regimen the risk of disease the of relapse on the that relapse and from is considered the in the of treatment for the of patients. patients are more the risk of relapse and than the risk of and follow-up are more as they more the the on the treatment the Hodgkin of for of cycles of escalated and depending on the of the this approach, the is with and and In PET2 patients DS < a reduction to only four cycles of to be to six or cycles of in of and in of treatment-related with four cycles of a that for as as In case the patient is DS ≥ he will a of six cycles of and toxicities of a of with only four the at further treatment The the of with BV at a reduction of in to the of an to from the first for which is the patient will be treated in an During safety assessments blood or and to assess at the of cycle will be delay or reduction are in case of or haematologic In case of after of (DS ≥ the patient will local with 30 the patient will the follow-up The patient will be for clinical follow-up at intervals at for years. a a physical examination, and some and and from treatment-related in the of fatigue is the in is associated with on and and on treatment as as for should be that patients can be as exercise or first and ASCT the of in patients with cycles of salvage or patients are with followed by this to of patients can be patients have been shown to from and ASCT with a ASCT in a maintenance therapy with BV ASCT should be considered in case of risk A revealed clinical risk factors in 3 months, bulk ≥ 5 ≥ 1 and to salvage, as decreased by or that an and risk for further treatment in patients with In and are by the patients and their and in some these can the In this in the management of a as the can be a In a ABVD is cycle using a PET/CT scan to the of treatment in have based on PET/CT as an imaging at diagnosis, interim and the and of this and other in management guidelines have not been in the of In this we on the management of patients with advanced in a The treatment and in this case are of we the of is the than the to and in this is followed by therapy with and therapy This patient's by the he to a centre for with lymph lymph and an initial evaluation a blood for and and We with a lymph node biopsy and to The with no or other evidence of The way to stage this patient is with a PET scan, a scan of the and would The patient that his is and he not have a or not been to for the six months, and the scan would more than his In the of these we would the scan would We that he has bulk at stage disease and blood an IPS of the is that he has bulk disease and regardless of PET/CT scan, would six cycles of followed by the mediastinal We plan with a chest X-ray, bone marrow and an of which are to this In advanced the regimen has been shown to be more than we continue to six cycles of ABVD in this This approach may be more are a and there is an risk of The economic of is to of therapy in some with and sometimes in the of high of The of treatment for at for six is one of the have on the approach based on interim PET with the of bleomycin after cycles if the interim PET2 is However, in this specific clinical with a a risk of bleomycin and an interim PET is not We plan for six cycles of ABVD in this We for a history of or and the to of in case of a history or is and bleomycin the a PET scan is in the a scan is for the of If not of the initial treatment plan bulk then assessment may of clinical and imaging with chest this approach, PET to patients who are to and using for those to PET scan, we have shown in these of The only in with the of ABVD the of If in the patient is to follow with blood and a clinical every six months for years. We not the patient to unless he is In case of a clinical we the and then the patient on the practice and the of the is the for in-patient therapy in the of the of therapy to salvage therapy and an adequate transplant are the of patients with disease are than we are to from and for patients to with an If the patient not respond to the first of salvage and is to further or in we would then with an regimen In we have patients on the regimen for in and have with and would not to this as a last in is with one of the with The to management is the patient's to treatment and therapy to these the and one of the of This patient is referred for evaluation of mediastinal to be advanced cancer. The initial evaluation should blood and blood as is one of the that can be from the of in with and or a blood that of the bone bone marrow by haematologists in is to the of the lymphoma or only a to the In the bone marrow biopsy is to a to further immunohistochemistry from haematologic is to be in the can be by a blood of and are of If the be by the computed tomography biopsy of the mediastinal mass by a should be to a a is to the results in a node is for initial evaluation by the If the is with would be to the clinical of The more for evaluation blood and the of lymphoma has been specific treatment should be and should be with contrast is for in patients according to the PET/CT can be in a of patients who can the of to our patient is with Hodgkin lymphoma stage as The on which specific treatment regimen should be is according to the lymphoma on IPS and His IPS is at four to male stage and is preferred over ABVD to the in using this regimen in this of patients. is not in The escalated regimen has been used by and by This regimen is given at a and of of bleomycin on of on of on 1 of on 1 of on of on and of on Moreover, can be used escalated if a is to escalated the of and is to and in of the and of this regimen is four cycles of escalated a scan with contrast is for If the patient four cycles of with site therapy at the of is If a can be cycles of escalated followed by is if no is the patient will be treated as the of a follow-up for of relapse and of treatment is interim physical examination, and every months for one then every six months year 3 then in patients for blood and after years years or at age if patients chest or at intervals after treatment is and ultrasound at intervals if is as and are in patients treated with or scan with contrast is not and is only for of relapse If relapse within months after a diagnosis, a of salvage regimen can be depending on and the patient's for and can be used according to If the is for the and and are in patients should on after their disease has and at to is therapy with is the of patients at first However, the of that have to is only a of patients can for maintenance therapy after in a high-risk of patients a relapse based on the 3 with patients who are to with relapse < months after therapy and relapse ≥ months after therapy with extra-nodal BV is and is not in the This with lymphadenopathy and a to and a colleagues the of an excisional and the merits of a with colleagues as of a who can excisional The followed by ultrasound biopsy approach by our colleagues may be as much a of potential resource as is on the process. should be the should be the of at to four for as as a for the of Hodgkin is a in the of these can be and a is to Hodgkin from and mediastinal which are of more in this age The global treatment the or that in the treatment of advanced stage Hodgkin of treatment on of the merits of approach should be by a patient imaging and patient for in a at and for is not with at one other in the management of Hodgkin lymphoma and the of the patient is in treatment should be in with the patient after an the of the and their and would to the of his and of the of for in the of is of if an escalated the of disease and factors to for some patients a approach is too patients are of for the to of and fertility the of fertility and in is in the with a approach by The is an escalated or a approach for a given In the in Hodgkin lymphoma the of bleomycin after cycles of ABVD in patients and the to escalated or in patients the for the of patients years and the The of of of bleomycin in cycles to six of However, in the of patients who there a in patients with advanced stage or high in the RATHL and this UK and the patient has the to for a interim PET after 2 of the RATHL approach if treatment with ABVD for this this clinicians in resource a is not will be by the relapse in patients ABVD with imaging as in this there is no the a if treatment with escalated The Hodgkin an approach, the escalated to only 4 cycles in the of patients who In this the is with a of with a years follow-up in we can only with this is 30 years The of not as the of a of patients ABVD or escalated of patient will always be by that of their the to not in this may a and in an of in salvage the for in-patient cycle which may in advanced management of fatigue after escalated Furthermore, the of after escalated is of the of patients who in and 30 Gy and of this regimen the the of a vs. escalated approach is of an ABVD vs. escalated approach, the and In the a of patients with risk stage a of of patients years and the age in a years of the for in patients of patients to years based on the of to an escalated The of a after cycles of escalated The of patients who to cycles of ABVD followed by a interim PET which if followed by further ABVD. This approach based on interim PET resulted in disease A of treatment of advanced the as the approach, fertility is and the RATHL approach is a approach, the be of the PET of the the of In a of than in of the DS of than the the to the patients in the RATHL if the A + AVD approach is colleagues to to the and a after not 3 cycles of A + in the the and clinical and not brentuximab vedotin for the and of escalated is feasible, to in with a colleagues are faced with to and as as approach to with biopsy and and of 6 cycles of ABVD for this in a resource In not to PET imaging and is the of may a is one an evidence The of the to the secondary and of the reduction in the from therapy to of may the of with escalated There is no for cycle from to be that the from the a patient with the escalated regimen only further cycles of escalated In patients with a for a PET is will the of patients to from guidelines that of clinical there is no for the and to patients from is there evidence to a for is a on for this fatigue and and weight management if and as as over of in the of the of biopsy and cycles of salvage followed by ASCT are and However, an of approach of in the In the of not the of brentuximab vedotin after The (and the merits of a or approach in the management of Hodgkin The in the treatment of advanced stage disease is to a escalated approach, the of the of However, on the is different and different to be at that in The and within which this is is a the to a understanding of this and and local us to in his and explore his treatment on approach, a There are no to the and the case The from the different their these and the