When to Not Use Combination and the Need for Bone Marrow Biopsy in HCL

Jae Park, MD: It’s an interesting perspective here, about rituximab, the cladribine-plus-rituximab issues. Farhad, do you give all your patients cladribine plus rituximab? Is there any other downside that you see? Are there patients for whom you probably wouldn’t consider adding rituximab?

Farhad Ravandi-Kashani, MD: We have continued this study. This is probably the longest-lasting study in our department and in our institution. It was opened in 2003 and still active. We still enroll to the study, and for that reason we still use it sequentially. Because we have had such good results, we didn’t feel the absolute need to do it concomitantly.

Now, I will tell you that more recently, in the last couple of years, because the NCCN Guidelines don’t even mention clinical trial as an option for frontline therapy of hairy cell leukemia specifically since cladribine or pentostatin, we’ve had some problems with insurance companies approving it, so we have treated some patients with cladribine alone. More recently, I have treated a couple of patients with cladribine alone because of COVID-19. They didn’t want to get the additional immunosuppression, and they weren’t keen on getting vemurafenib for whatever reason. So yes, we are still using that strategy, and I can tell you the responses continue to be durable many years later.

Jae Park, MD: How about the goals of a therapy for these patients? Obviously the first goal is the reversal of their cytopenia. Some of the questions that occasionally come up after they get therapy, and they get a bone marrow biopsy after 4 months. Or does everybody even need a bone marrow biopsy after getting this type of a therapy if they have a normal blood count? Then the second is that when they do get it, despite the fact that their blood count is normal because of the persistent presence of a hairy cell leukemia, some of these patients may end up getting a recommendation for another line of therapy, which may be important for another topic to just clarify here. Are there any comments on the need for bone marrow biopsy and what to do with the bone marrow biopsy information?

Alan Saven, MD: In my practice I don’t do post-treatment bone marrow as long as the blood counts are normalized. If there are ongoing cytopenias, I elect to defer that bone marrow, but I don’t do it routinely. I don’t treat the minimal residual disease [MRD]. If I’m going to use the Rituxan, I’m going to use it up front. I’ll wait and see, but I don’t treat people based on minimal residual disease. Just to go back to Dr Ravandi-Kashani, I tend to use the combination more in younger patients than older patients. I’m not sure they need to be disease-free for longer periods of time, because chances are they’re going to die of something else. I don’t routinely do a post-treatment bone marrow. Dr Coutre mentioned that you could do a bone marrow at 4 months. I have data that patients can be positive at 3 months, negative at 6 months; positive at 6 months, negative by 9 months; positive at 9 months and gone at 12 months. It’s important when you do your minimal residual disease. Six months may not be long enough. I was the filler doing all the bone marrows in all these patients, and what struck me was that we didn’t know exactly when to do that, and some people will convert only at 1 year. I’m not quite sure what it means. Dr Ravandi-Kashani’s study I didn’t think required a bone marrow at 4 weeks. You just did it.

If you’re going to use Rituxan, just do it. I’m not sure a follow-up bone marrow is going to provide all that much information outside a clinical research study. I noticed there are consensus reviews in everything else. Always call for a post-treatment marrow, but I’m not sure what you do with that information except upset the patient.

Steven Coutre, MD: I fully agree. I don’t do routine bone marrow in practice. Occasionally, you do see a patient referred to you who’s had a post-treatment bone marrow and still has some detectable disease, and they want to know what to do, or that it’s already been acted on, for example. That is a slippery slope, I must say. I always teach the fellows that if you’re going to do a task, ask yourself what you’re going to do with that information. Right now I would not act on detectable minimal residual disease if a bone marrow was done.

Farhad Ravandi-Kashani, MD: I agree. Outside the setting of a clinical trial, I don’t think there is any need to do a repeat bone marrow except, for example, if you have a patient who is 6 months out and still has significant cytopenias. That’s the situation that I would do a bone marrow. I agree that probably 3 months is not the best time to do the bulk bone marrow. You can be positive at 3 months and become negative at 6 months or, as Alan said, even further out. And also in terms of MRD, Dr Saven has a paper that looked at some patients 17 years out. They still had some hairy cells in their bone marrow, and they were not having any problems. This is a huge debate, and it’s not something that can be settled in a short period of time.

Jae Park, MD: I agree. I quote that paper a lot, Dr Saven. It is quite interesting because you actually do a bone marrow biopsy in patients who have completely normal blood counts. Then in a serial bone marrow biopsy you actually detect them, with no clinical consequence, in need of a therapy. But when they do, it does upset the patients and raises all sorts of questions from their perspective, understandably. What does that mean? What do you do with that information?

Having good expert opinions and groups giving the thoughts [is important] because some may get another therapy unnecessarily that they don’t need for many years or ever. It’s an important point to bring out and encourage, obviously to discuss with their physicians and/or second opinions if that ever comes up.

Transcript Edited for Clarity