The 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago is usually more about solid tumors than lymphomas and leukemia such as CLL, but there were still three important abstracts to review when Carol Preston of the Patient Power team (http://www.patientpower.info ) asked me about my personal quick impressions from the meeting.
Take Away Points
- Less new CLL research is presented at ASCO compared to the hematology meetings such as ASH (American Society of Hematology)
- Three CLL presentations stood out in my assessment
- A new simpler tool to prognosticate and guide therapy.
- First trial combining a triple punch of a 3rd generation anti-CD20 mAb, a PI3Kδ and BTK inhibitor shows no new safety concerns.
- Bendamustine with ibrutinib is superior to bendamustine alone in previously-treated CLL patients.
I attended the oral presentation by Prof. Michael Hallek on abstract 7002: The international Prognostic Index for patients with CLL (CLL-IPI): An international meta-analysis. He presented a simplified prognostic rating index for chronic lymphocytic leukemia (CLL) that looked at which factors really made a difference in patient outcomes and therefore in their suggested management.
The five factors that rose to top in terms of their significance were:
- Clinical stage
- del(17p) and/or TP53 mutation
- IGHV mutation status
- β2-microglobulin (B2M) level
Whether these will continue to be important in the era of oral targeted therapies is yet to proven in my mind.
The abstract can be accessed here.
Abstract 8501: Safety and activity of the chemotherapy-free triplet of ublituximab, TGR-1202, and ibrutinib in relapsed B-cell malignancies:
While not restricted to CLL patients, and used in only a handful of patients, this abstract was the first to show the safety of the potentially potent triple combination of 1) a novel glycoengineered mAb (monoclonal antibody) targeting a unique binding site on the CD20 antigen, 2) a next generation, once daily, PI3Kδ inhibitor (think idelalisib or Zydelig and duvelisib or IPI-145), and 3) ibrutinib or Imbruvica. Overall response rate was 87% in a difficult to treat population but there were only 2 CLL patients and a total of 7 patients assessed. What I really liked about this phase I trial is not the impressive response rates, but the good news that no new problems arose with combining these potent therapies.
I believe we are going to need these types of cocktails (especially one such as this with no chemo component!) to reach a cure. More of these combo trials are needed and surely will be coming to a research center near you soon.
The abstract can be accessed here.
Bendamustine with and without ibrutinib:
The third trial I mentioned was much larger; a Phase III trial involving 578 previously-treated CLL patients. It demonstrated that adding ibrutinib to bendamustine improved the overall response rate (ORR) from 67.8% to 82.7% with similar results in high-risk patients. To its credit, the trial allowed crossover for those who did progress on bendamustine alone.
This late-breaking abstract 7005 can be found here.
My burning unanswered question is not whether adding ibrutinib to bendamustine improves our outcomes compared to using bendamustine alone. This abstract suggests that it does and that is no surprise. What I want to know is whether adding bendamustine to ibrutinib improves our outcomes compared to using ibrutinib as a solo therapy. For me, that is far from proven.
My fast impressions on these three presentations from ASCO 2015 are just that, my opinions, and are not mean to replace a more rigorous analysis of the data and further research to answer the unanswered questions.
Here’s the interview:
Brian Koffman 8/18/15