iwCLL 2019: Dr. Danielle Brander on Bendamustine and Rituxan (BR) versus Ibrutinib Based Therapies for Frontline Treatment of Chronic Lymphocytic Leukemia (CLL) in Elderly Patients

At iwCLL 2019 in Edinborough, Dr. Danielle Brander of Duke University in Durham, NC updates the breakthrough data originally presented that compared the most widely used chemotherapy for older, (defined as 65 or older) CLL patients versus ibrutinib based therapy for front line older patients. She also presents some subgroup analysis.

Here is my interview with Dr. Woyach of Ohio State, the lead author from ASH 2018 to set the stage.

Here is her full article from the prestigious New England Journal of Medicine.

Takeaways:

• There were 3 arms, BR versus ibrutinib alone versus ibrutinib and rituximab.
• Bendamustine is milder intravenous chemotherapy that works by damaging DNA.
• Ibrutinib is an oral targeted therapy that blocks preferentially blocks pro-survival pathways in CLL and has revolutionized treatment in chronic lymphocytic leukemia.
• Rituximab is a monoclonal antibody that improves the efficacy of most chemotherapy that is used to treat CLL, but how much benefit it adds to targeted therapies such as ibrutinib had not been clear.
• This study found that ibrutinib based therapy significantly improved how long patients survived without disease progression (Progression Free Survival or PFS) compared to BR.
• Adding rituximab to ibrutinib did not improve PFS, unlike the benefit seen when it is added to chemo drugs.
• As would be expected, patients with deletion 17p (del 17p) did much worse with chemo (BR).
• Patients with Complex Karyotype or CK (in this study defined as 3 or more chromosomal abnormalities found in the CLL clone) did just as well on ibrutinib as those with less complexity.
  • This was somewhat unexpected as a prior study had suggested that CK was a prognostic factor for a poor outcome for patients on ibrutinib, but in that trial design, CK patients with deletion 17p were not separated out. It appears that patient with CK but not with del 17p do very well on ibrutinib.
  • Some believe that the cut off to define CK in CLL should be 5 or more chromosomal abnormalities found in the clone, not 3. See this from Dr. Kay at the same meeting on that important topic.
• There was also no difference between in mutated and unmutated IGVH for ibrutinib therapy unlike the big difference in duration of response seen with chemo.
• There were significant adverse events in this older population.

Conclusions:

The data is getting stronger and stronger. When patients have the option to take ibrutinib versus BR, ibrutinib should be the choice for most. There should be no role for any chemo in patients with del 17p. This study is to be lauded for looking at the elderly, an understudied population in CLL. We still need to look at how we best stratify this huge group of patients who can be so different in their health even if they are the same in their age.

Here is my iwCLL interview with Dr. Brander done in Scotland in October 2019.