Expert perspectives on the MAGNOLIA trial and novel BTK inhibitor zanubrutinib in the context of marginal zone lymphoma treatment.
Bhavesh Shah, RPh, BCOP: Amit, you mentioned the MAGNOLIA trail. I want to get your perspective on that. I hate to do cross talk comparison, but we’re going to have to do that. Javier mentioned that we saw a difference in bleeding, atrial fibrillation, and maybe even hypertension. I want to touch on that and get your perspective on the MAGNOLIA trial.
Amitkumar Mehta, MD: Javier briefly talked about MAGNOLIA. It was a phase 2 multicenter study involving zanubrutinib 160 mg twice a day in various marginal zone lymphomas. As Javier mentioned, the updated results showed a very impressive overall response rate of 74%. The important difference in efficacy was that the complete response rate was significantly higher compared with ibrutinib. Ibrutinib had just a 4% complete response rate compared with zanubrutinib, which was almost 24% or 25%. That was impressive. This was a small number of patients: 68. That doesn’t represent all marginal zone lymphoma. What flavor you get in your clinical trial dictates a different outcome.
The striking difference was the toxicity profile. As you mentioned, the high specificity for BTK [Bruton tyrosine kinase] was the key, and less specificity for TEC and EGFR kinases led to a slightly different BTK inhibitor profile. Atrial fibrillation, bleeding, and bruising were lower with zanubrutinib compared with ibrutinib. That was the major difference. Ibrutinib taught us that atrial fibrillation, bleeding, and bruising are the class effect, and I still believe that. More specifically, those class effects are lesser with BTK inhibitors. Acalabrutinib is also similar in line and highly specific with less atrial fibrillation, and the new kid on the block, LOXO-305, a noncovalent BTK inhibitor, have very low rates of atrial fibrillation, bleeding, and bruising. It depends how these kinase inhibitors are binding to BTK with what specificity and whether they’re covalent that decides the toxicity profile of these agents.
Bhavesh Shah, RPh, BCOP: Based on my assessment of looking at events such as atrial fibrillation and hypertension, there’s a flat rate with zanubrutinib, but with ibrutinib, you see it creeping up every year. It continues to go up. It’s important to understand that, because these patients are going to be on long-term therapy. There’s this increased risk. It’s important to have pharmacists treating some of these toxicities, where we have primary care–trained pharmacists helping treat the hypertension for these patients and then optimizing the atrial fibrillation medications. There are drug interactions. Having this medically integrated model with pharmacists is a key for managing adherence and toxicities for these patients.
The other caveat is: I haven’t crunched the numbers, but I’ve also heard that zanubrutinib may be lower cost. If you look at it head to head vs ibrutinib and acalabrutinib, the estimation is about $500 for a 30-day supply of acalabrutinib and about $1400 for 30 days of ibrutinib. Those are interesting possible disrupters of market.
Transcript edited for clarity.