ADC, and I apologise for the pun but we thought we’d liven things up this morning on a Saturday, refers to antibody drug conjugate, which I’ll be talking about, which is a novel therapy for a particular unmet need in a common population of patients with lymphoma.

So, as many of you might realise, diffuse large B-cell lymphoma is a type of aggressive non-Hodgkin lymphoma and it is the most common type of non-Hodgkin lymphoma.

While this is very curable in a large number of patients, despite our best standard upfront therapy, which generally involves immuno-chemotherapy or R-CHOP for many of these patients, about 40% of patients either won’t respond to initial therapy or ultimately relapse despite that initial therapy.

As a next line treatment, many of these patients are considered for high-dose chemotherapy and stem cell transplant as a potential next curative attempt.

Unfortunately many patients are not eligible for transplant due to age or comorbidities, and the treatment options for these transplant-ineligible patients or patients who relapse after transplant are really limited.

Survival is generally quite short and really the responses to successive therapy actually worsens with multiple relapses.

So we certainly do need better treatment options for this group of patients.

At this meeting I’ll be presenting a phase II trial exploring the use of a novel agent, polatuzumab vedotin.

This is a first in class anti-CD79B antibody drug conjugate.

CD79B is a protein that’s present on the surface of many normal B-cells and is typically universally expressed, on diffuse large B-cell lymphoma as well as follicular lymphoma.

This antibody drug construct is essentially an antibody targeting CD79B, so it specifically seeks out the tumour target.

It’s attached to a toxin and when it attaches to the tumour cell it actually gets absorbed into the tumour cell and the toxin is selectively released into the tumour.

So it’s a way of specifically delivering the toxin to the tumour cell while trying to protect the normal body cells.

In this phase II trial that I’ll be presenting, it enrolled patients with relapsed refractory diffuse large B-cell lymphoma, and it was a head-to-head comparison of polatuzumab vedotin in combination with bendamustine and rituximab, versus bendamustine and rituximab alone.

The primary end-point of the trial was the CR rate as determined by PET scanning at the end of treatment, and this was significantly higher in patients receiving the polatuzumab vedotin with the BR, so it was 40% versus 15%.

Importantly this translated into a significant improvement in progression free survival, which was almost tripled with a median progression-free survival of 6.7 months versus 2 months, and also quite remarkably into an improvement in overall survival, which more than doubled with the median being over 11 months compared to under 5 months.

So in this randomised phase II trial it really is the only, so far, head-to-head comparison of a novel targeted agent against the standard therapy in this patient population that’s ineligible for stem-cell transplant, and it demonstrated that the combination of polatuzumab vedotin with BR significantly improved the response rates, progression free survival as well as overall survival.

Based on these encouraging results this drug has been granted breakthrough therapy designation, both by the US FDA as well as PRIME designation by the EMA, and it will be explored further in other combinations in on-going studies.