ASCO: 2018: Dr. Pagel on the Important CLL (chronic lymphocytic leukemia) Research

Dr. John Pagel out of Swedish Hospital in Seattle reviews the top CLL abstracts presented at ASCO (American Society of Clinical Oncology) Annual Meeting held June 1-5, 2018 in Chicago.

Although ASCO is better known for its research on solid tumors, there is an increasing number of important chronic lymphocytic leukemia abstracts being showcased for the professional oncology community at its huge annual meeting.

Take-aways:

• The CAPTIVATE trial looked at using ibrutinib and venetoclax (I+V) frontline in 163 patients, mostly with high-risk prognostics. The data is only in the first 14 patients.
  • By using ibrutinib alone first for 3 months, the tumor burden was reduced lowering the risk of TLS (tumor lysis syndrome) when venetoclax was added.
  • Early data showed an amazing 100% response rate with an MRD (minimal residual disease) negative response in 82% of the frontline patients.
  • No significant increase in toxicity was observed with the combination versus the drugs alone.
  • We do not have data beyond 15 months.
• Umbralisib (TG-1202) is an experimental PI3Kδ that was studied in 40 patients who were intolerant (but not progressing) on a prior BTK or PI3K inhibitor, mostly ibrutinib.
  • Intolerance, but not disease progression, is the most common reason for ibrutinib discontinuation in “the real world data” so this is a significant unmet need.
  • No patients discontinued umbralisib as a result of prior drug intolerance. Diarrhea was the most common side effect.
  • Medium PFS (progression free survival) was not reached with 90% of patients showing progression free at a medium follow up 6.5 months (range 1–15).
• The MURANO trial venatoclax and rituximab (VenR) versus BR (bendamustine and rituximab) for R/R (relapsed and refractory) CLL, demonstrated that any VenR patients independent of high-risk factors such as deletion17p, IgVH unmutated, and mutated TP53- can be become MRD negative.
  • 84% of all patients reached MRD- status in the peripheral blood with little difference between the various prognostic groups.
  • It can happen as fast as in 4 months and the number climbs over time.
  • 83% maintained MRD– and were PFS free at median follow-up of 13.8 (5.6–23.0) months.
  • 2 developed progressive disease; 2 died; 2 developed Richter’s and 15 (12%) converted to confirmed MRD+ (2 serial assay positive) at median MRD+ follow-up of 5.6 (0.03–11.2) months.
• All of these trials are demonstrating the advantages of targeted treatments alone or in combinations over the cytotoxic (cell killing) chemotherapy that was traditionally used in CLL until very recently.
• This is critical: While all these trials showed remarkable responses and good tolerability, they have yet to demonstrate what we patients should really care about, a long-term survival advantage. That must wait for longer follow-up.

Here is a link to the CAPTIVATE trial ASCO abstract: https://meetinglibrary.asco.org/record/159485/abstract

Here is a link to the umbralisib trial ASCO abstract: https://meetinglibrary.asco.org/record/162369/abstract

Here is a link to the MURANO trial ASCO abstract: https://meetinglibrary.asco.org/record/159489/abstract

Here is my SKYPE interview with Dr. John Pagel:

Summary:

As we have previously explained, there are many reasons for CLL patients to be optimistic.

• While the numbers are small in all these studies, frontline combination therapies without chemo are achieving MRD – results in the vast majority of patients.
• Relapsed and refractory patients are achieving similar positive results.
• There are now several effective and well tolerated options for patients who are intolerant of ibrutinib.

What we don’t know yet is whether these MRD negative responses lead to deep and durable survivals and dare we whisper, a cure for our CLL. Only time will tell.