Ryan W. Jacobs, MD

We’re all looking for potential breakthroughs. Things are turning in the right direction for the country as a whole in terms of decreasing case counts and deaths from the coronavirus. There are still areas that are seeing increased cases though, and of course we’re all worried about the potential of a resurgence, either with reopening or perhaps in the fall and winter. We don’t know what will happen, and we want to try to be as prepared as possible. There was a big breakthrough with remdesivir (Gilead Science), and so we do have a treatment option for the most sick patients in intensive care settings with coronavirus, but availability of that drug has been pretty limited. Only certain hospitals received a supply of it, and I’m not too familiar with projected increase in production, so we would like to have more treatment options. Without knowing when or if a vaccine is coming, the more immediate answer to our problems would be a treatment to try to reduce morbidity and mortality. With a drug like ibrutinib, that’s exciting because it is a readily available drug that has many approvals, so I think supply would be less of an issue — most specialty pharmacies are stocked with it. So, it would potentially be much more readily available than remdesivir.

It’s great that there’s a trial going on and nobody’s jumping to any conclusions. The Blood publication is a reflection of our current times, in that we’re all hoping to try to find something. This was an observational report with a very limited patient number. It does look promising in that as a whole, the six patients in the report overall did better than what would be expected based on the available reports of poor outcomes in COVID-19 patients with concomitant hematologic malignancies. The example of the one case in the series where the patient was taken off the lower dose of ibrutinib and decompensated and then restarted at a higher dose and seemed to improve is particularly compelling. Still, it is just six patients but there is some reason to potentially be excited. I’m glad that there’s an organized clinical trial going on at a renowned institution like Dana-Farber where they can look at around 50 patients and see if use of ibrutinib would improve outcomes. The proposal of how BTK inhibition (which is what ibrutinib does) can potentially improve outcomes in COVID-19 patients is through decreased production of downstream inflammatory cytokines in the lungs. I think it’s an interesting proposed mechanism of action and gives us reason to hope that BTK inhibition could prove useful in preventing respiratory failure in COVID-19 patients.

My research focus is in chronic lymphocytic leukemia, where ibrutinib is most commonly used. Our lymphoma team at the Levine Cancer Institute has helped contribute real-world data to a CLL outcomes consortium that is led primarily by Anthony Mato, MD, MSCE, who is the head of the CLL Program at Memorial Sloan-Kettering Cancer Center. Through our outcomes group we were able to accumulate data on over 200 patients with CLL who were infected with coronavirus. The mortality rates in patients with CLL were similar to what we had seen with other hematologic malignancy patients. They are quite high mortality rates, coming in around 30%. In this group of CLL patients that we looked at, a large number were on ibrutinib or some other BTK inhibitor at the time of their coronavirus infection. Among patients on BTK inhibitors, the mortality rates were similar to those patients who were either on observation or who were on a different kind of CLL treatment. Because of this observation, I am a bit less optimistic that the Dana-Farber-led study with ibrutinib is going to provide a significant breakthrough. There was a caveat in the data that we looked at though. The majority of the time when patients on a cancer treatment come in with an infection, their treatment is stopped. This was the case with the majority of the patients that we observed — their BTK inhibitors were stopped when they were admitted with COVID-19. So perhaps that was the reason why we didn’t seem to observe any differences in mortality in this group of patients. Clearly, ibrutinib didn’t appear to be necessarily protective against getting the infection. I think what the Dana-Farber study may ultimately help answer is whether or not administration of ibrutinib during infection can actually improve outcomes like reducing mortality, and so I’ll be excited to see the results of that study. In the interim, I will likely choose to continue BTK inhibition in patients that present with COVID-19 while on treatment with BTK inhibitors like ibrutinib.

Given where we are at with really only one FDA-approved treatment — remdesivir, which is in quite limited supply still — if we get a compelling study with 50 patients, although that is a small number and it’s largely at a single institution, I think that would hopefully be enough for the FDA to react and give a contingent approval for the use of ibrutinib, and there would seemingly be low risk in allowing for its use if the study was compelling enough. It’s a very safe drug. It is given indefinitely in its treatment of B-cell malignancies and has low discontinuation rates and low complication rates. With the seemingly low risk and if the study shows a reward, hopefully that study would support contingent approval while larger studies were undertaken.