Venetoclax With Rituximab Treatment and Safety Profile

Ian W. Flinn, MD, PhD:So we’ve adopted the venetoclax/rituximab treatment option for patients with relapsed CLL [chronic lymphocytic leukemia] in a number of our patients. And that experience has really been quite good. We know now that you can safely give venetoclax for the vast majority of patients in an outpatient setting, ramping up the venetoclax and being able to avoid tumor lysis.

So it is a little bit of a burden, I think, in terms of the 5-week ramp-up that occurs with venetoclax, but in my experience, it’s well worth it in terms of the long-term payoff. And so, I’m really now using this in a lot of my patients in that first relapsed setting for patients with CLL.

The safety profile of the venetoclax/rituximab combination, I think, fares well when compared to other treatment options. For instance, it certainly fares well compared to a chemotherapy such as bendamustine/rituximab. You don’t have nearly the collateral damage you see with the indiscriminate cytotoxicity seen with bendamustine. There are cytopenias that occur with venetoclax. One has to be cognizant of that. You have to follow patients in terms of making sure they don’t develop neutropenia most predominantly. That’s usually very easily managed with either dose adjustment or the use of myeloid growth factors.

I think I previously mentioned the issue with tumor lysis syndrome. This was an initial concern with venetoclax; it remains a concern. But in my experience, this can easily be handled for the majority of patients as an outpatient.

The ramp-up dosing of venetoclax is a minor inconvenience for people that occurs over 5 weeks, a minor convenience for the patients, a little bit for the offices. But the long-term payoff of this, the synergies that’s seen with this combination, the depth of remission that was seen with this, I think is well worth that.

I think that there’s been concern with community physicians about using venetoclax-based therapies. And … that came out of some very early trials … for which there was tumor lysis syndrome seen. For most doctors and most community practices, they can use this combination of venetoclax and rituximab very easily and very safely. The only issue, I think, that occurs in doctors’ offices is doing the tumor lysis syndrome monitoring. You really do have to get turnaround of the electrolytes in rapid fashion, especially during the first few dose escalations—and you have to pay attention to that. If you do that and you have the ability to extend, if chemistry is off, get them back the same day within a few hours, get a STAT redout, I don’t think there’s really very much a barrier at all for this.

We know that we can risk stratify patients for tumor lysis syndrome based on focal disease. So patients with large bulky lymph nodes, patients with high white count versus those patients with lower counts. And it’s really a continuum, but we still tend to think of it as sort of 3 different groups: high, intermediate, and low. And so you’re probably going to need to do CT scans on patients to understand what the largest lymph node is for patients. You’re going to need to, of course, measure their lymphocyte count. But there’s a relatively available algorithm that risk stratifies patients based on size of lymph nodes, and I would definitely take a look at that and understand what your patient’s risk is. You can mitigate some of the risk in terms of the dose escalation, the ramp up that happens. But the other thing is, of course, putting patients on allopurinol, that will help. In a rare instance you have to use rasburicase to lower patients’ uric acid. But that’s pretty rare.

Transcript edited for clarity.

A 71-Year-Old Man With CLL

• A 71-year—old man presented with symptoms of persistent fatigue and weight loss
• PMH: Left axillary lymph node, 1.5 cm X 1.5 cm
• PE: Left axillary lymph node, 1.5 cm X 1.5 cm
• Laboratory findings:
  • WBC, 133,000; 85% lymphocytes (ALC, 68,000 cells/mL)
  • Hb; 11.4 g/dL
  • Platelets; 111 X 10⁹/L
  • ANC; 174/mm³
• Molecular testing:
  • Flow cytometry; CD19++, CD5+, CD20+, CD23++, CD38+
  • IgVHmutated
  • FISH, +12
• β2M, 3.0 mg/L
• Diagnosis; chronic lymphocytic leukemia
• BM biopsy; CLL in 88% of cells
• The patient was treated with ibrutinib and achieved a complete remission within 5 months
• 13 months later, the patient reported extreme fatigue; now with 3.0 X 3.0-cm lymph node
• Laboratory findings:
  • Repeat FISH: remained +12
  • WBC, 225 X 10⁹/L
  • HB, 9.6 g/dL
  • Platelets, 103 X 10⁹/L