Choosing a PI3K Inhibitor in Relapsed Follicular Lymphoma

Christopher R. Flowers, MD:So I think, importantly, in a follow-up publication to the originalNew England Journal[of Medicine] study, …our group that was involved in the development of idelalisib also looked at patients who were early relapsers after therapy. And those early relapsers actually had responses to idelalisib and had progression-free survival that was similar to the population of the trial as a whole. So even for patients who are early relapsers after chemoimmunotherapy, idelalisib appears to be an effective agent and 1 that has very similar progression-free survival to its use in follicular lymphoma in the relapsed setting as a whole.

So I think when we think about the 3 PI3 kinase inhibitors that are available now, they differ slightly in terms of the experience that we’ve had with using them, with idelalisib being the 1 that’s been first to market and the 1 that we have most experience with from clinical trial and treatment of patients on therapy after its approval. Copanlisib is an IV [intravenous] PI3 kinase inhibitor [that is] given intravenously on a weekly basis for 3 weeks in a row followed by 1 week off. From the perspective of some investigators, giving an IV agent is better than giving an oral agent in that you have complete control of the management of the patient and control of the administration. From my perspective, and some others’ perspective, it is much preferred to give an oral agent to patients than having them come into the office and being forced to have intravenous therapy once weekly for a prolonged period of time.

The other thing that we see with copanlisib is that it is an agent that inhibits both alpha PI3 kinase as well. And with that alpha inhibition there are other effects that happen during the infusion of the IV medication, particularly hypertension is something that can occur and needs to be monitored for, and hyperglycemia is something else that can occur and needs to be monitored.

For this patient who had type 2 diabetes and was already on insulin, copanlisib may be a less preferred therapy in that particular setting. And so that’s something that needs to be monitored fairly closely for that particular patient population.

So nonadherence is something that is of definite concern for patients in a number of different settings. Nonadherence can occur [both] in the IV setting and in the oral setting for a number of reasons. I think it’s very important for people who are on oral agents, particularly since those are oral agents that are expected to be administered chronically. And for the majority of these agents, they are pills that work as long as patients are taking them. And as soon as they stop taking the pills, generally the effectiveness of the therapy goes down, unlike chemotherapy that is administered for a time-limited fashion and then stopped.

And so adherence is something that needs to be attended to by patients and nurses and pharmacists anytime we see patients in the practice setting. And what I typically do for my patients is ask them, how many pills have they missed over the period of time since I have seen them last, and do pill counts to try [to] figure out how adherent they are with therapy.

Transcript edited for clarity.

Case:A 72-Year-Old Woman With Relapsed Follicular Lymphoma

H & P:

• A 75-year-old woman presented with severe fatigue and weight loss
• Was diagnosed with inguinal contiguous stage II follicular lymphoma (FL) 4.5 years ago; completed BR and achieved PR that persisted for almost 4 years
• Started treatment with R-CHOP for extensive mediastinal FL 6 months ago; had achieved PR by 3 months before symptoms returned
• PMH: Type 2 diabetes X 10 years, controlled on basal insulin and SGLT2 inhibitor
• PE: Swelling present in right axillary lymph nodes; not tender to touch; no crackles or rales in lungs; no history of pneumonia; has received flu and PPV23 vaccination
• ECOG performance status: 1
• Biopsy showed grade 2 FL without transformation
• Labs:
  • eGFR = 72 mL/min/1.73²
  • AST/ALT: within normal range
  • ANL: 1350 /mm³
  • Platelets: 100,00 /µL
  • Hemoglobin: 10 g/dL
  • LDH: 275 U/L
• Imaging: PET/CT revealed axillary lymphadenopathy, with largest mass 7.2 cm
• She was started on idelalisib 150 mg b.i.d.
• After 10 days, she called with concerns about diarrhea, which she has been experiencing on average 4 times daily for the past few days