ASH 2018: Dr. Lindsey Roeker on the CORE trial for CLL (chronic lymphocytic leukemia) Patients

We have a great many choices of medications to treat our chronic lymphocytic leukemia, but how to best use and sequence them is still an active area of research.

At ASH 2018, Dr. Roeker of Memorial Sloan Kettering Cancer Center in NYC discusses a large long term registry trial, the Core study,  to answer those questions with real world data.

The CLL Collaborative Study of Real-World Evidence (CORE) is a retrospective, multicenter, international, collaborative observational study of patients with CLL treated at either community or academic sites between 2012 and 2018 with either chemotherapy/chemoimmunotherapy (CT/CIT) as 1st-line treatment or with novel agents.

Takeaways:

• 351 pts were studied. 179 received CT/CIT and 172 received novel agents as 1st-line therapy.
• Most patients were treated in community settings (81%).
• The median ages were 62 and 66 years for pts receiving CT/CIT and novel agents, respectively.
• Demographics were generally similar between CT/CIT and novel agent groups with one exception:
  • 17p deletion/TP53 mutations were present in 20% who received novel agents, compared to only 4% who received CT/CIT (p <0.0001). Remember, no patient with 17p (del) should receive CT/CIT, but 14 patients did.
• The most common 1st-line CT/CIT treatments were BR or bendamustine + rituximab (56%; 101/179), followed by FCR or fludarabine + cyclophosphamide + rituximab (20%), chlorambucil + obinutuzumab (8%), and fludarabine + rituximab (5%).
• The most common novel-agent based therapies were ibrutinib (80%; 138/172), ibrutinib + rituximab (7%), and venetoclax-based treatments (7%).
• 30% (16/53) of patients discontinued their novel agent due to completed scheduled duration of treatment.
  • This is hard to understand as the only novel medication that could have had a scheduled duration of treatment is venetoclax and that was only used by 7% of the patients. Moreover, during most of the period studied there was little data to support fixed duration therapy for any novel agent.
• Regardless of 1st-line therapy, >80% of patients received a novel agent-based therapy as 2nd-line treatment.

CONCLUSIONS:

There are many worrisome findings in this very early data.

• A few patients who absolutely should not get CT/CIT are still getting it.
• 30% of patients were stopping novel agent therapy after a fixed duration, which is hard to understand. For the 138 patients on ibrutinib the guidelines are to treat until intolerance or disease progression, not after they have completed a scheduled duration of treatment.
• Bendamustine + rituximab was by far the favored CIT, but it does not offer the possibility of long-term remissions that are seen in >50% of those with favorable markers treated with FCR. In healthy younger (<65 years old) patients who can tolerate it and opt for CIT, FCR would generally be the recommended option.
• The circumstances where a patient would receive CT/CIT as second line therapy would be very unusual, but nearly 1 in 5 patients did.

This is a very early look at the data in a long-term study designed to determine how novel therapies and treatment sequencing impacts adverse events and outcomes in the treatment of CLL.

It also serves as yet another reminder of why it is so important to have a CLL expert on your team.

Here is a link to my ASH 2018 interview with Dr. Lindsey Roeker.

Here is the ASH 2018 CORE abstract