Idelalisib's Value in Follicular Lymphoma

Peter Martin, MD:Idelalisib was approved by the FDA on the basis of a phase II clinical trial. And in that clinical trial, a group of physicians around the country treated people with rituximab- and alkylator-refractory follicular lymphoma. So, in other words, we treated a group of patients who were probably more resistant to therapy than this patient, where they had to have relapsed within 6 months of rituximab and within 6 months of receiving an alkylator. And in that patient population, over 50% of people responded, and they had a median PFS of close to a year. So, about 11 months.

In a group of people who really didn’t have a lot of other great treatment options, there was promising activity. And importantly, most of the people treated on that clinical trial felt a lot better than they had during their prior therapies. Not only that, but they responded significantly better to idelalisib than they had to their last prior therapy. So, it was a good option that said idelalisib does have some drawbacks, well known from the package insert in particular, which I recommend. If anybody is using idelalisib, it’s worthwhile to review that. These include liver enzyme abnormalities. It’s important to monitor the liver enzymes when we’re starting with idelalisib. And again, then there are some autoimmune disorders that start to become more common in people on idelalisib for longer periods of time. These can include pneumonitis and colitis specifically, which is, I think, the case in this patient.

So, somewhere around 15% to 20% of people receiving idelalisib may develop an autoimmune colitis based on clinical trials. We don’t know whether that number would go up if people were on it for a longer period of time, but we may learn with some time. We don’t really know how to predict who is likely to experience that. Autoimmune colitis is clearly different from the drug-induced colitis that people experience early on or drug-induced diarrhea, which is just a simple diarrhea that goes away. It might happen when they start idelalisib, and then it goes away within the first month or two. An autoimmune colitis is usually one that is delayed in terms of onset and can become pretty significant. So, we monitor for it. And if we see it or if we see something that we’re suspicious of, then the guidelines say if the diarrhea is relatively mild to just monitor it and consider a dose reduction. My bias in this case is that if we’re becoming a little bit more significant and having an impact on her quality of life, just hold it and wait for it to resolve.

In summary, I think idelalisib is a reasonable choice in this situation because it accomplishes what the goals were in this case. In other words, this was a woman who was relatively young but had multiple prior therapies and was interested still in maintaining a reasonable quality of life. Idelalisib is an oral therapy, so it’s easy to do. It requires some blood monitoring and some clinical monitoring after that. But it doesn’t require a lot of intravenous infusions, doesn’t cause hair loss, is relatively easy to administer, and is easy to take, and as long as we’re cognizant of the potential side effects and looking for them and being ready to act on them, it’s something that can be done relatively easily.

Transcript edited for clarity.

March 2012

• A 57-year old woman presented with lymphadenopathy
• PE: marked swelling in the right supraclavicular region, non-tender
• Laboratory findings: platelets, 98,450/mL; HB, 10.9 g/dL
• CT imaging showed a 4-cm right supraclavicular mass and a diffuse pattern of right-sided enlarged inguinal nodes
• Incisional biopsy, pathology
  • IHC: CD10+, BCL2+, CD23(-), CD43(-), CD5(-) CD20(+), BCL6 (-)
  • Grade 2 follicular lymphoma, 12 centroblasts/HPF
• FLIPI-intermediate
• The patient was started on bendamustine/rituximab and achieved a partial response after 6 months

February 2016

• Four years later, the patient complains of increasing fatigue
• PET/CT shows intense FDG uptake in the right inguinal region and in the left hilar region; SUVmax of 9
• The patient was started in lenalidomide + rituximab
  • After 3 months, her symptoms have resolved
  • After 6 months, she has achieved a partial response with significant shrinkage in the inguinal lymph node

February 2018

• Two years later, the patient now age 63 years, reports having severe fatigue and weight loss; she requires frequent rest during the days and has trouble keeping up with daily activities
• Performance Status, ECOG 1
• Laboratory findings: platelets, 104,000/L; Hb, 9.9 g/dL; LDH, 342 U/L
• PET/CT shows generalized lymphadenopathy bilaterally in the pleural and pelvic regions; FDG uptake in the liver
• Liver enzymes, WNL
• The patient was started on idelalisib 150 mg b.i.d.
• Follow up imaging at 3 months showed significant regression in the liver and pulmonary nodes and stable disease in the pelvic region
• After 4 months on therapy she began to experience watery diarrhea, 5 to 6 times per day