[Table, Cost-effectiveness evidence]. - Non-Hodgkin's Lymphoma: Diagnosis and Management

Recommendation	Consider consolidation with autologous stem cell transplantation for people with chemosensitive mantle cell lymphoma (that is, there has been at least a partial response to induction chemotherapy) who are fit enough for transplantation.
Relative value placed on the outcomes considered	Progression free survival was the critical outcome when drafting the recommendation. Other important outcomes for this topic included overall survival, disease free survival, progression free survival, treatment related mortality, treatment related morbidity and health related quality of life. No evidence for health related quality of life was identified.
Quality of the evidence	The quality of the evidence was very low to moderate as assessed using GRADE methodology. Evidence was downgraded for imprecision, study design limitations and indirectness. Apart from one randomised trial comparing autologous transplantation with interferon- α, the evidence came from non-randomised, comparative studies. For this reason the guideline committee were not able to make a strong recommendation.
Trade off between clinical benefits and harms	The GC thought the recommendation to consider autologous transplantation would prolong progression free survival; the evidence suggested a median progression free survival improvement of almost 2 years with autologous transplantation. The use of high dose therapy with autologous transplantation however was associated with toxicity including late effects and in some cases treatment related mortality. The GC considered that the increased progression free survival outweighed the harms due to late effects which can be managed and to some extent mitigated by surveillance.
Trade off between net health benefits and resource use	No economic evidence was identified and no economic model was built. The resource implications associated with the recommendation were thought to be negligible because the use of autologous transplantation as consolidation of induction chemotherapy is the current standard of care for people with chemosensitive mantle cell lymphoma. In comparison to the alternative courses of action, autologous transplantation was thought likely to be cost-effective. There would be increased costs associated with transplantation (in comparison to chemotherapy alone) with an autologous transplantation estimated to cost £34,000. However, the evidence suggested that progression free survival should be greatly improved with an autologous transplantation. These improvements would be expected to translate into superior effectiveness in QALY terms. The GC thought that it was likely that the strategy would be cost-effective in cost per QALY terms. This view is partially supported by extrapolating from the economic analysis conducted for this guideline in another NHL subtype. In patients with follicular lymphoma, it was found that autologous transplantation was cost-effective in comparison to chemotherapy with an ICER of £4,812 per QALY. Thus, it was demonstrated that autologous transplantation was cost-effective despite the high costs of initial therapy because of the substantial gains in effectiveness.
Other considerations	The GC considered that patients with pre-existing co-morbidities are unlikely to be candidates for autologous transplantation and that this will disproportionately affect older patients. The GC therefore based their recommendations on patient fitness rather than age. The GC chose not to make a research recommendation about upfront consolidation with allogeneic transplantation because a comparative study would not be feasibile.

Recommendation

Consider consolidation with autologous stem cell transplantation for people with chemosensitive mantle cell lymphoma (that is, there has been at least a partial response to induction chemotherapy) who are fit enough for transplantation.

Relative value placed on the outcomes considered

Progression free survival was the critical outcome when drafting the recommendation. Other important outcomes for this topic included overall survival, disease free survival, progression free survival, treatment related mortality, treatment related morbidity and health related quality of life.

No evidence for health related quality of life was identified.

Quality of the evidence

The quality of the evidence was very low to moderate as assessed using GRADE methodology. Evidence was downgraded for imprecision, study design limitations and indirectness.

Apart from one randomised trial comparing autologous transplantation with interferon- α, the evidence came from non-randomised, comparative studies. For this reason the guideline committee were not able to make a strong recommendation.

Trade off between clinical benefits and harms

The GC thought the recommendation to consider autologous transplantation would prolong progression free survival; the evidence suggested a median progression free survival improvement of almost 2 years with autologous transplantation. The use of high dose therapy with autologous transplantation however was associated with toxicity including late effects and in some cases treatment related mortality.

The GC considered that the increased progression free survival outweighed the harms due to late effects which can be managed and to some extent mitigated by surveillance.

Trade off between net health benefits and resource use

No economic evidence was identified and no economic model was built.

The resource implications associated with the recommendation were thought to be negligible because the use of autologous transplantation as consolidation of induction chemotherapy is the current standard of care for people with chemosensitive mantle cell lymphoma.

In comparison to the alternative courses of action, autologous transplantation was thought likely to be cost-effective. There would be increased costs associated with transplantation (in comparison to chemotherapy alone) with an autologous transplantation estimated to cost £34,000. However, the evidence suggested that progression free survival should be greatly improved with an autologous transplantation. These improvements would be expected to translate into superior effectiveness in QALY terms. The GC thought that it was likely that the strategy would be cost-effective in cost per QALY terms.

This view is partially supported by extrapolating from the economic analysis conducted for this guideline in another NHL subtype. In patients with follicular lymphoma, it was found that autologous transplantation was cost-effective in comparison to chemotherapy with an ICER of £4,812 per QALY. Thus, it was demonstrated that autologous transplantation was cost-effective despite the high costs of initial therapy because of the substantial gains in effectiveness.

Other considerations

The GC considered that patients with pre-existing co-morbidities are unlikely to be candidates for autologous transplantation and that this will disproportionately affect older patients. The GC therefore based their recommendations on patient fitness rather than age. The GC chose not to make a research recommendation about upfront consolidation with allogeneic transplantation because a comparative study would not be feasibile.

From: 4, Management

Non-Hodgkin's Lymphoma: Diagnosis and Management.

NICE Guideline, No. 52.

National Guideline Alliance (UK).

London: National Institute for Health and Care Excellence (NICE); 2016 Jul.

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