EHA-SWG Rare Lymphomas: The role of the microenvironment in CLL and rare lymphomas

On March 10th, at the EHA-SWG Rare Lymphomas Scientific Meeting 2017 in Barcelona, Spain, Martin Dreyling chaired a session on Lymphoma Biology. The second presentation of this session was by Marcel Spaargaren, of the Academic Medical Center, Amsterdam, The Netherlands, on the topic of ‘The Role of the Microenvironment’. A summary of the data presented and discussed are detailed below:

  • Using ibrutinib in CLL resulted in transient increase in lymphocytosis in a saw-tooth like pattern
  • Data suggested no direct killing of CLL cells, indicating that CLL cells are mobilized out of tumor and then killed
  • Ibrutinib inhibits BTK-mediated control of integrin-mediated and cytokine-controlled adhesion and migration in primary CLL cells
  • The four-week on, one week off regimen aids this process vs. continuous treatment

  • Similar data are seen in MCL and WM (in terms of PR)
  • Ibrutinib resistance was seen in ~30% CLL and MCL patients, 15% of resistance due to mutations in BTK and PLCγ2
  • Combination therapy with ibrutinib and idelalisib, a PI3K inhibitor, may help prevent resistance, as seen in the data presented

  • However, in WM, lower efficacy was seen only in patients with CXCR4 gain-of-function mutations (Treon et al., 2015. NEJM) possibly indicating that CXCR4 mediated adhesion is important in WM

In summary, Marcel Spaargaren stated that inducing anoikis in these malignancies is a broad strategy that may result in fewer non-responders due to it not relying on a single growth or survival signal. Therefore, exploiting the relationship between the tumor microenvironment and lymphoma cells was stated as being the ‘Achilles’ heel’ of lymphoma.

 

References:
  1. Spaargaren M. The Role of the Microenvironment. 2017 Mar 10. EHA-SWG Rare Lymphomas. Barcelona, Spain.