bring together everything NICE says on a topic in an interactive flowchart. are interactive and designed to be used online. They are updated regularly as new NICE guidance is published. To view the latest version of this NICE Pathway see: http://pathways.nice.org.uk/pathways/non-hodgkins-lymphoma NICE Pathway last updated: 20 March 2018 This document contains a single flowchart and uses numbering to link the boxes to the associated recommendations. Page 1 of 10
Page 2 of 10
1 Person aged 16 or over with diffuse large B-cell lymphoma No additional information 2 Central nervous system prophylaxis Explain to people with diffuse large B-cell lymphoma that they have an increased risk of central nervous system lymphoma if the testis, breast, adrenal gland or kidney is affected. Explain to people with diffuse large B-cell lymphoma that they may have an increased risk of central nervous system lymphoma if they have 2 or more of the following factors: elevated lactate dehydrogenase age over 60 years poor performance status (ECOG score of 2 or more) more than one extranodal site involved stage III or IV disease. Explain that the level of risk increases with the number of factors involved. Offer central nervous system-directed prophylactic therapy to people with diffuse large B-cell lymphoma: that affects the testis, breast, adrenal gland or kidney or who have 4 or 5 of the factors associated with increased risk of central nervous system relapse listed above. Consider central nervous system-directed prophylactic therapy for people with diffuse large B- cell lymphoma who have 2 or 3 of the factors associated with increased risk of central nervous system relapse listed above. 3 Radiotherapy after first-line immunochemotherapy Consider consolidation radiotherapy delivering 30 Gy to sites involved with bulk disease at diagnosis for people with advanced-stage diffuse large B-cell lymphoma that has responded to first-line immunochemotherapy. For each person, balance the possible late effects of radiotherapy with the possible increased need for salvage therapy if it is omitted, and discuss the options with them. Page 3 of 10
4 When to offer fluorodeoxyglucose-positron emission tomography-ct imaging Do not routinely offer FDG-PET-CT imaging for interim assessment during treatment for diffuse large B-cell lymphoma. Offer FDG-PET-CT imaging to assess response at completion of planned treatment for people with diffuse large B-cell lymphoma. Consider FDG-PET-CT imaging to assess response to treatment before autologous stem cell transplantation for people with high-grade non-hodgkin's lymphoma. 5 Salvage therapy Multi-agent immunochemotherapy Offer salvage therapy with multi-agent immunochemotherapy to people with relapsed or refractory diffuse large B-cell lymphoma who are fit enough to tolerate intensive therapy: explain that this is primarily to obtain sufficient response to allow consolidation with autologous or allogeneic stem cell transplantation, but is also beneficial even if not followed by transplantation consider R-GDP immunochemotherapy, which is as effective as other commonly used salvage regimens and less toxic. Stem cell transplantation Offer consolidation with autologous stem cell transplantation to people with chemosensitive diffuse large B-cell lymphoma (that is, there has been at least a partial response to chemotherapy) who are fit enough for transplantation. Consider consolidation with allogeneic stem cell transplantation for people with chemosensitive diffuse large B-cell lymphoma (that is, there has been at least a partial response to chemotherapy): that relapses after autologous stem cell transplantation or in whom stem cell harvesting is not possible. Page 4 of 10
Pixantrone monotherapy The following recommendations are from NICE technology appraisal guidance on pixantrone monotherapy for treating multiply relapsed or refractory aggressive non-hodgkin's B-cell lymphoma. Pixantrone monotherapy is recommended as an option for treating adults with multiply relapsed or refractory aggressive non-hodgkin's B-cell lymphoma only if: the person has previously been treated with rituximab and the person is receiving third- or fourth-line treatment and the manufacturer provides pixantrone with the discount agreed in the patient access scheme. People currently receiving treatment initiated within the NHS with pixantrone monotherapy that is not recommended for them by NICE in this guidance should be able to continue treatment until they and their NHS clinician consider it appropriate to stop. NICE has written information for the public on pixantrone. 6 Follow-up For people in complete remission after first-line treatment with curative intent for diffuse large B- cell lymphoma: offer regular clinical assessment consider stopping regular clinical assessment aimed at detecting relapse 3 years after completing treatment for people in ongoing complete remission offer urgent appointments to people who experience a recurrence of lymphoma symptoms or new symptoms that suggest disease relapse do not offer lactate dehydrogenase surveillance for detecting relapse do not offer routine surveillance imaging (including chest X-ray, CT and PET-CT) for detecting relapse in people who are asymptomatic. Quality standards The following quality statement is relevant to this part of the interactive flowchart. 4. End-of-treatment summary plan Page 5 of 10
7 Monitoring after treatment See Non-Hodgkin's lymphoma/non-hodgkin's lymphoma overview /Monitoring after treatment Page 6 of 10
Why we made the recommendations on obinutuzumab Current first-line treatment for symptomatic advanced follicular lymphoma is induction therapy with rituximab plus chemotherapy, followed by maintenance treatment with rituximab when there has been a response to induction therapy. The main evidence on the effectiveness and safety of obinutuzumab is from an ongoing clinical trial. It shows that obinutuzumab plus chemotherapy followed by obinutuzumab maintenance treatment delays disease progression more than current treatment. However, it also shows that undesirable side effects are more common with obinutuzumab than with rituximab. There are not enough data to know with certainty whether obinutuzumab increases life expectancy. The company's revised economic analyses focuses on higher-risk subgroups. Obinutuzumab costs more than branded rituximab and even more than the biosimilar versions of rituximab. However, using the preferred assumptions and the discounted prices for obinutuzumab and rituximab, the cost-effectiveness estimate for obinutuzumab plus chemotherapy followed by obinutuzumab maintenance treatment, compared with rituximab plus chemotherapy followed by rituximab maintenance treatment, is lower than 30,000 per quality-adjusted life year gained. Therefore, obinutuzumab is recommended as an option for untreated advanced follicular lymphoma in patients at higher risk. For more information see the committee discussion in the NICE technology appraisal on obinutuzumab for untreated advanced follicular lymphoma. Glossary CHOP cyclophosphamide, doxorubicin, vincristine and prednisolone CVP cyclophosphamide, vincristine and prednisolone FISH fluorescence in situ hybridisation Page 7 of 10
FDG-PET-CT fluorodeoxyglucose-positron emission tomography-ct H. pylori Helicobacter pylori MALT mucosa-associated lymphoid tissue PET-CT positron emission tomography-ct Sources Non-Hodgkin's lymphoma: diagnosis and management (2016) NICE guideline NG52 Pixantrone monotherapy for treating multiply relapsed or refractory aggressive non-hodgkin's B- cell lymphoma (2014) NICE technology appraisal guidance 306 Your responsibility Guidelines The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals and practitioners are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or the people using their service. It is not mandatory to apply the recommendations, and the guideline does not override the responsibility to make decisions appropriate to the circumstances of the individual, in consultation with them and their families and carers or guardian. Local commissioners and providers of healthcare have a responsibility to enable the guideline to be applied when individual professionals and people using services wish to use it. They Page 8 of 10
should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with complying with those duties. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. Technology appraisals The recommendations in this interactive flowchart represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, health professionals are expected to take these recommendations fully into account, alongside the individual needs, preferences and values of their patients. The application of the recommendations in this interactive flowchart is at the discretion of health professionals and their individual patients and do not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian. Commissioners and/or providers have a responsibility to provide the funding required to enable the recommendations to be applied when individual health professionals and their patients wish to use it, in accordance with the NHS Constitution. They should do so in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. Medical technologies guidance, diagnostics guidance and interventional procedures guidance The recommendations in this interactive flowchart represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, healthcare professionals are expected to take these recommendations fully into account. However, the Page 9 of 10
interactive flowchart does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer. Commissioners and/or providers have a responsibility to implement the recommendations, in their local context, in light of their duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity, and foster good relations. Nothing in this interactive flowchart should be interpreted in a way that would be inconsistent with compliance with those duties. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. Page 10 of 10