Determining When to Treat and First-Line Therapy for HCL

Jae Park, MD: Let’s begin with Andrea, perhaps with just a brief overview of the indications for treatment. Do all patients with hairy cell leukemia need therapy? Can some of them be observed with monitoring alone?

Andrea Sitlinger, MD: Hairy cell is treatable, and we can get very long remissions with cladribine and pentostatin. It’s not curable, and most patients will relapse at some point. You don’t necessarily need to treat right away. There are 3 big reasons to treat. One would be significant cytopenias. If you have a neutrophil count that’s less than a 1000 mm3, if your hemoglobin is less than 11 g/dL, if your platelet count is less than 100,000 mm3, those are all indications that the hairy cell is causing significant issues, and you’re at higher risk for infection. If you’re having symptomatic splenomegaly or other symptomatic adenopathy, and lymph nodes are not the most common thing but certainly do occur, and constitutional symptoms if they are significantly impairing activities of daily living. Those could all be reasons to treat.

Jae Park, MD: Dr Saven, can you start us off with some of the first-line therapy options for patients with hairy cell leukemia. I know we talked about some pure analog, and there are a couple of choices there. When would you choose 1 versus another, and perhaps a little about your schedules and how is it administered?

Alan Saven, MD: In ideal circumstances that purine nucleoside analog is the treatment of choice. You’ve got 2 real choices: 1 is cladribine, or 2-chlorodeoxyadenosine, and the other is pentostatin. Cladribine historically was given as a single week of infusion. There was in vitro data showing that prolonged exposure was better than brief exposure, and it’s the continuous infusion for a week.

There was 0.1 mg/kg per day by continuous infusion for 7 days. Ultimately, that became a hardship because people needed a catheter and a PICC [peripherally inserted central catheter], and the catheter got infected, so we converted to 0.14 mg/kg per day every 7 days over 2 hours for 5 days, and that represents 0.14 mg/kg over 2 hours each day. There hasn’t been a direct comparison, but if you look at the results, they’re almost identical.

We give it now as a 2-hour infusion over 5 days, and it’s 1 cycle of therapy. We give it intravenously, but there are preparations in which you can give it subcutaneously. Years ago we did a PK study showing that you can actually give it orally. If you double the dose and give it orally, you can achieve the same levels. But at Scripps [Health in San Diego, California] in 2020, we give it as a 2-hour infusion times 5 days. Pentostatin is another treatment available as first-line therapy. It’s given every other week, 4 mg/m2 IV, but it’s more protracted therapy. It’s given every other week for 3 to 6 months, so not surprisingly, cladribine has emerged as the treatment of choice because of its convenience. At the beginning of our studies we’re going to exclude actively infected patients. We appreciated the immunosuppression of this drug, and people had to have the infection stricken before they started.

People who champion pentostatin initially didn’t have that exclusion, and you could receive the drug on this study. I still wouldn’t use either purine nucleoside analog in the presence of active infection. There have been a number of publications about whether you can combine cladribine with anti-CD20 rituximab. The way Dr Ravandi-Kashani did it was you give the cladribine, you wait a month, and then you give 8 weekly doses of rituximab. The NCI [National Cancer Institute] has given it on day 1 and then weekly times 8, together with the 5 initial doses of the cladribine.

You can achieve a deeper level of response, ie, lower minimal residual rates. Whether that’s clinically important or not, and if it’s worth the extra immunosuppression that’s going to follow is the subject of debate in the age of the coronavirus and the fears about immunosuppression. If you elect to use a purine nucleoside analog, you may or may not want to add the rituximab given the prolonged immunosuppression that is likely to follow.

Interferon, the magic product that was on the cover of Life magazine many years ago, was approved to treat hairy cell leukemia. It subsequently had other uses. I haven’t used interferon for many decades, but there is a role for it, probably in actively infected patients. If you can get hold of vemurafenib, a BRAF inhibitor, it may be a role for interferon. If you have a pregnant patient and she’s not a candidate for splenectomy in the second trimester, maybe there’s a role for interferon. But the remissions from interferon are not very deep. Most of them have partial remissions, taking retracted therapy over the course of the year and self-injections of a medication. It’s not commonly used anymore. Also, if you use interferon after a purine nucleoside analog, it’s very unlikely to work. Other safety concerns, not really. Blood counts may get worse before they get better, and with cladribine it has about a 40% incidence of neutropenic fever. But despite the incidence of neutropenia, at least at Scripps, we’ve seen rare infections.

That’s how I approach new patients with hairy cell leukemia. There are emerging data about the role of vemurafenib as frontline therapy. There are studies at Memorial Sloan Kettering [Cancer Center] in combination with obinutuzumab. But that’s in the realm of research rather than standard of care. But in the day of the coronavirus, when you don’t want to immunocompromise patients, that is a consideration.

Transcript Edited for Clarity