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Transforming standards of care and treatments for lymphoid cancers

Our research spans from the molecular analysis of the changes that take place as cells transform from normal lymphocytes into lymphoid malignancies, through the testing of novel treatment strategies drawing on this knowledge, to large scale clinical trials which change practice internationally.


Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with 3,700 new cases in the UK each year, while lymphoma is the fifth most prevalent cancer in the UK, with more than 14,000 new diagnoses annually. Insights from Southampton research have been used to shape new standards of care internationally, develop new therapeutic drugs and optimise these treatments through clinical trials. 

Novel therapies for Chronic lymphocytic leukaemia (CLL)

Improved CLL treatment
Improved CLL treatment

Professors Freda Stevenson and Terry Hamblin discovered a prognostic marker for two types of CLL, namely mutated CLL (M-CLL) and unmutated CLL (U-CLL). The latter is the more aggressive subset, having a mean survival of eight years, compared to 25 years for M-CLL.

The discovery of this marker generated widespread interest in CLL among biologists. Further research by Professors Francesco Forconi and Graham Packham led to new therapeutic strategies specifically targeting the B-cell receptor (BCR) signalling pathway that gives rise to the marker. These therapies were the first-in-class ibrutinib and the second generation acalabrutinib.

Ibrutinib was first approved for CLL by the US FDA in 2014 and by NICE in 2017 for use on the NHS. Acalabrutinib received FDA approval in 2017 and EU approval in 2020.

The clinical benefits and economic impact of these therapies, initially derived from Southampton’s observations, has been vast, transforming CLL treatment by challenging the prior dominance of chemoimmunotherapy regimens. Annual sales revenues of ibrutinib alone reached more than £5 billion in 2019, while sales of acalabrutinib were almost £400 million the following year.

PET imaging in lymphoma

PET scan of someone with lymphoma
PET scan of someone with lymphoma

Beginning in 2008, Professor Peter Johnson led the CRUK-funded phase 3 RATHL trial, which demonstrated the value of PET imaging to guide the intensification or de-escalation of chemotherapy in advanced Hodgkin lymphoma. This technique optimises the balance between efficacy and toxicity.

RATHL also demonstrated that the drug bleomycin, a treatment that can cause lung damage and had been used in chemotherapy for 30 years, could be omitted without compromising cure rates.

Both these findings have translated into clinical practice in the UK, wider Europe and the US.

The international IELSG 26 trial, also led by Professor Johnson in Southampton, demonstrated the benefit of PET imaging in primary mediastinal lymphoma. This was cited in the 2016 ESMO guidelines.

Obinutuzumab for follicular lymphoma

The GALLIUM study for which Southampton led the correlative laboratory studies, demonstrated that progression-free survival for patients treated with the novel anti-CD20 antibody obinutuzumab (80%) was superior to that seen with the previous standard rituximab (73%) when given with chemotherapy. 

Citing the GALLIUM results, the US FDA and the EU approved obinutuzumab as a treatment, in combination with chemotherapy, for follicular lymphoma in 2017. 

In March 2018, NICE recommended obinutuzumab ‘as an option for untreated advanced follicular lymphoma in patients at higher risk’. 

Rituximab for follicular lymphoma

In the phase 3 Southampton-led trial SABRINA, the maintenance antibody therapy for follicular lymphoma, rituximab, was shown to be equally effective and safe when given subcutaneously as intravenously. This was shown to increase convenience for patients and reduce healthcare costs by 25%, or a total of €6,000 for the full course of treatment. 

As a direct result of SABRINA, the subcutaneous version of rituximab received approval for common forms of NHL from the EU in 2014 and the US in 2017. In 2014, NICE cited SABRINA as providing key evidence for its use. 

Rituximab has been one of Roche’s best-selling drugs, with £5 billion in global sales in 2015.

Key Publications

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