Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE)

[Jm954]

The Lancet, Feb22nd 2021. Jeff P Sharman, Mato et al

Patients with chronic lymphocytic leukaemia and high-risk features (TP53mutated, 11qdel, and 17p del) have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, to ibrutinib therapy in this population.

126 patients were enrolled and randomly assigned to receive ublituximab plus ibrutinib (n=64) or ibrutinib alone (n=62) between Feb 6, 2015, and Dec 19, 2016. After a median follow-up of 41·6 months (IQR 36·7–47·3), the overall response rate was 53 (83%) of 64 patients in the ublituximab plus ibrutinib group and 40 (65%) of 62 patients in the ibrutinib group (p=0·020). Remember these are relapsed and refractory patients.

Two patients in the ublituximab plus ibrutinib group died due to adverse events (one cardiac arrest and one failure to thrive), neither of which were treatment-related. Five patients in the ibrutinib group died due to adverse events, including one cardiac arrest, one cerebral infarction, one intracranial haemorrhage, one Pneumocystis jirovecii pneumonia infection, and one unexplained death; the death due to cardiac arrest was considered to be treatment-related.

The addition of ublituximab to ibrutinib resulted in a statistically higher overall response rate without affecting the safety profile of ibrutinib monotherapy in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia.

More here: thelancet.com/journals/lanh...

Jackie

[SofiaDeo]

This is very exciting! TY for posting this. I am wondering if we will see future trends of multi therapy regimens with slightly lower doses (to minimize side effects) to improve outcomes & prevent cancer resistance.

[Smakwater]

Better, But needs to be more better.

Guess I'll just stay healthy for a while longer.

Thanks for the heads up.

JM

[Jm954 Administrator in reply to Smakwater]

It's another possible treatment option, even if it's only in a clinical trial.

[Smakwater in reply to Jm954]

In the sense of modern research, I am pro-trial.

Without them, we would still be seeing medieval barbers who use leeches and bleeding to treat anemia.

[cartwheels]

You say relapsed is had one prior treatment but what was there prior treatment ? Had any been on inbrutinib mono therepy before and then on this trial added the cd 20 ? Thanks Jackie

[Jm954 Administrator]

Prior BTKi was an exclusion criteria for this trial. Her are the inclusion and exclusion criteria.

Inclusion Criteria:

Previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment

At least one high-risk cytogenetic feature defined by the presence of 17p deletion, 11q deletion and/or p53 mutation

Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

Exclusion Criteria:

Any major surgery, chemotherapy or immunotherapy within the last 21 days

Evidence of hepatitis B virus, hepatitis C virus or known HIV infection

Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded

Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)

Previous therapy with ibrutinib, or any drug that specifically inhibits Bruton's tyrosine kinase (BTK)

Jackie

[bennevisplace]

In response to cartwheels, the Lancet summary doesn't say which prior treatment(s). You may find out by purchasing one-time access.

It does say that subjects had ECOG status of 2 or lower, meaning they were not in great physical shape. Results are encouraging.

[Jm954 Administrator in reply to bennevisplace]

Just look up the trials reference number to get the info.Jackie

[Jm954 Administrator in reply to bennevisplace]

ECOG score 0-2 is actually the fitter groups of patients not the more frail ones.

GRADE ECOG PERFORMANCE STATUS

0 Fully active, able to carry on all pre-disease performance without restriction

1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

2 Ambulatory and capable of all self care but unable to carry out any work activities; up and about more than 50% of waking hours

3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours

4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair

5 Dead

Jackie

[bennevisplace in reply to Jm954]

Ah yes I see I misinterpreted the meaning of 2 or lower. Thanks.

[LeoPa]

What is a failure to thrive?

[Justasheet1]

Typically someone very old and sick who is bedridden and doesn’t eat and drink much; end of life.

[Oleboyredw-uk]

What quaint wording “a failure to thrive”.

best (and better) to all, rob

[Jm954 Administrator in reply to Oleboyredw-uk]

Usually used in respect of infants and young children in UK. I've seen this diagnosis used fairly often.Jackie

[Justasheet1 in reply to Jm954]

Jackie,Using it for children would be so sad and tragic. It was often the admitting diagnosis for nursing home patients in the hospital that I worked at.

But I looked it up and you are correct that it is commonly used for infants and small children 😢

Jeff