New Drug Combo for B-Cell Lymphoma: How Effective Is It? | Babis Andreadis, MD

Hi, I'm Babs Andriades. I run the lymphoma program at the University of California in San Francisco. And at this ASH meeting, I was excited to present some new data regarding improvement of outcomes for patients with B-cell non-Hodgkin lymphoma with the addition of novel agents to immunotherapy. So the immunotherapy that has been making the news over the last several ASH meetings now has been by specific antibodies, which are antibodies that engage not only the target, in our case lymphoma cells, but also the T cells, so producing an immune response. And these antibodies have made their way across all lines of therapy for patients with follicular lymphoma and diffuse large B-cell lymphoma. The other side of the equation, though, is that there's patients who unfortunately don't respond to those treatments, so we're always looking for combinations to improve their effectiveness. A new class of drugs called cell mods that essentially is an acronym for drugs that mobilize or utilize the cell's machinery to essentially activate the immune system, but also help cancer cells die faster has emerged. And this class of drugs has shown promise in early studies in patients with both follicular and diffuse large B-cell lymphoma. So our study aimed to combine by specific antibodies with this class of drugs to help augment the by specific antibody activity. So we enroll patients across a variety of institutions, both in the US and abroad, with later stages of follicular lymphoma and diffuse large B-cell lymphoma. So our patients had many prior treatments, on the average three, and some of them had up to six prior lines of therapy. Many of the patients had received CAR T cells, about a third of the patients. Almost 100% of the patients had received prior chemotherapy and antibody treatments. So this was a group of patients who were running out of options. So we examined two by specific antibodies, one called Mosuna Tuzumab and one called Clofidumab, which both have different approvals in the US and abroad. And we did two parallel cohorts where we treated patients with either antibody and then two different dose levels of this oral cell mod agent called Calcite. And after we did an early analysis that showed that the combination was safe, we did an expansion to see how effective it was. So in terms of safety and tolerability, we didn't really find any added toxicity. One of the concerns for people getting by specific antibodies is this thing called cytokine release syndrome, which is a way essentially for the immune system to activate and cause side effects, off-target side effects. And we found that adding this immune booster to the by-specifics didn't really increase the chance of side effects. On the other hand, when we look at effectiveness, we found that actually we had very high response rates. So in patients with follicular lymphoma treated with either combination, Mosuna Tuzumab and Golka or Clofidumab and Golka, the very high response rates approaching 100%. And many of the response rates were complete responses, which means we couldn't see any residual disease on subsequent PET scans. In patients with diffuse large B-cell lymphoma, we saw a very high number of responses as well, about two thirds of the patients responding and many of those about half being complete responses. We did some additional analysis and show that in people who had previous CAR T-cell therapy, so these are kind of patients who were pretty sick going in, most of these patients had a response. So in one of the arms, five of the eight patients had a complete response, in the other all five patients had a major response, so four complete, one partial. So we were excited about the results of this study. It doesn't really prove that the combination should be the next standard of care, but it actually provides enough data to launch new studies now to study further. If our videos have helped you in any way and you're able to, please consider making a donation to help us continue this important work. Your gift will go three times as far when we reach $500,000 by the end of the year. Every contribution, big or small, makes a difference and we're deeply grateful for your support.