Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingClinical development of the antibody-drug conjugate denintuzumab mafodotin in combination with chemotherapy for patients with CD19-positive DLBCL
2:42 minutes.
TRANSCRIPTION:
DR LOVE: So ever since we first started to hear about B-vedotin, I’ve been wondering when any more antibody drug conjugates are going to come into the lymphoma field. None have been approved. But there was a paper at ASH looking at denintuzumab mafodotin, targeting CD19. What were your thoughts about that? DR FLOWERS: So that is an interesting agent that has been looked at in B-cell malignancies, because CD19 is nearly ubiquitously expressed, kind of like CD20. I think it’s also an interesting approach, because the vast majority of people will lose CD20 as they relapse and have had multiple, multiple regimens with rituximab, either with chemotherapy or, in some cases, as maintenance therapy with follicular lymphoma and in other settings that you’ve seen. DR LOVE: So they lose it? You mean, you test them and they’re not CD20-positive? DR FLOWERS: Correct. So some of those patients will become CD20-negative. Now, we presume that there still is CD20 on some set of the population. And we commonly will still use rituximab with their chemotherapy. But there is a subset of patients who you cannot detect CD20 easily, either, by flow cytometry most commonly. So this is an approach that has been looked at in patients with CD19-positive malignancies. It is now moving forward in diffuse large B-cell lymphoma as an approach used in combination with RICE therapy in the relapsed setting. One of the concerns about anti-CD19 antibody-drug conjugates is, there may be overlapping toxicity with the toxicity that’s seen and in terms of ocular toxicity. In many of those trials, they need very careful ophthalmologic exams, and with serial uses of the agent, that ocular toxicity is something that can become more prominent. And so likely the best uses for these agents are using them in combination with therapy and for a brief duration of use. And so I think the use in combination with RICE therapy as a relapsed setting, where you’re only using a few numbers of doses of the CD19 antibody-drug conjugate, is a useful one. Likewise, CD19 is the target for CAR T-cell therapy. And so I think one of the things that will come into question is, between these competing approaches, whether CAR T cell as an approach or antibody-drug conjugates as an approach would be a preferred approach for that particular target. |