Safety/Efficacy of Idelalisib in Follicular Lymphoma

Ajay Gopal, MD:Idelalisib is a new class of drugs. This was the first-in-class drug approved of PI3K inhibitors. Any time one uses a new class of drugs, it’s important to understand the unique toxicity profile. What we learned from this trial in double-refractory indolent B cell lymphoma, as well as other trials in CLL and other B cell histologies, is that it does have a unique toxicity profile and people need to be aware of it. There are a variety of side effects that need to be monitored. These include GI toxicity. There’s often early diarrhea that occurs. If it’s grade 1 or 2, this can be managed with symptomatic management, making sure there’s not infectious cause, of course, and anti-motility agents. However, if patients have grade 3 diarrhea—this often occurs more late in the course, usually around 7 months or more after being on therapy—this is more of an inflammation colitis if biopsies have shown a lymphocytic infiltrate. And this typically needs to be managed, certainly at grade 3. We need to hold the drug and manage with corticosteroids, either systemic or nonabsorbable corticosteroids.

The other early toxicity that one needs to monitor is LFT elevation. This typically happens over the first 6 to 8 weeks, and patients need to have their transaminases monitored at least every other week by labs over the first 2 to 3 months. Often times, if these are simply less than 5 times the upper limit of normal, this can be just watched. However, if these go beyond 5 times the upper limit of normal of transaminases, then typically the drug is held until they normalize, and most patients can restart then at the 100 mg/twice a day dose rather than the starting 150 mg/twice a day dose.

One also needs to be mindful of the potential infectious complications with this agent. There have been cases of PJP (pneumocystis jiroveci pneumonia) that have been observed in patients treated with idelalisib. In general, I tend to prophylax my patients either with trimethoprim/sulfamethoxazole or with dapsone for PJP prophylaxis, and CMV reactivation has also been noted. So, the current recommendations suggest considering CMV monitoring, and certainly in the early phases, most of the CMV cases occurred in the early treatment course. We often will check CMV PCR on our patients on this drug.

In terms of other major safety concerns, there is a low rate of pneumonitis that needs to be monitored. So, certainly, if people have pulmonary symptoms, this needs to be evaluated. Otherwise, , there really are no significant cardiovascular complications or high rates with this drug. Taking those at that adverse event profile, why was this drug approved? This was approved based on the efficacy, as I mentioned. In the follicular cohort, there was a 54% overall response rate and the overall duration of response was about 12.5 months in this double-refractory population.

My personal experience with this drug is that it is effective. It works in follicular lymphoma, but one does have to monitor the toxicities and follow the patients closely. It’s very tempting, when one has a pill, to write a prescription and let your patients go. But these pills do have side effects and we need to follow our patients closely.

Transcript edited for clarity.

January 2014

• A 66-year-old male presents with bilateral inguinal and right axillary adenopathy.
• Past medical history includes hypercholesterolemia managed with simvastatin; moderate hypertension, managed with hydrochlorothiazide/triamterene; history of atrial fibrillation managed with apixaban.
  • Laboratory findings: hemoglobin level 10.2 g/dL, LDH elevated
  • CT scan shows widely disseminated disease, with bulky adenopathy in the pelvis, mesentery, retroperitoneum, supraclavicular region, and aortopulmonary window. The largest lymph node is 9.8 cm.
  • Chest radiography shows small bilateral pleural effusions
  • Bone marrow biopsy shows 70% involvement with FL
  • Excisional biopsy shows grade 2 follicular lymphoma
• The patient was started on R-CHOP and achieved remission for 19 months at which time he developed an enlarging adenopathy in the pelvis.

October 2015

• Upon relapse of her disease, the patient was treated with bendamustine/rituximab.
• He achieved a partial response for close to 6 months.

April 2016

• The patient reports feeling tired and abdominal fullness.
• Physical exam remarkable for palpable splenomegaly.
• PET imaging showed enlargement of pelvic and retroperitoneal nodes and development of several new lesions.
• The patient was started on idelalisib therapy.