Follicular Lymphoma: Second-Line Therapy Options

Ajay Gopal, MD:This patient, unfortunately, had a relatively early relapse after R-CHOP therapy and needed second-line therapy. The question comes up as to what the best second-line therapy is in these early relapse patients. As I mentioned, I don’t think we really know the right answer here. Bendamustine/rituximab is reasonable. It’s a very standard, traditional approach. Typically, for patients that are young like this patient—and 66 years old is still quite young—we would expect a 20-year life span for somebody who’s otherwise healthy and 66 years old. I will talk about alternative strategies, I’ll talk about clinical trials. We talk sometimes about high-dose therapy and autotransplant if patients have sensitive disease, but we’re really trying to think of different strategies because we know the traditional approach typically yields an unacceptably short overall survival for those that relapse early. However, bendamustine/rituximab is still a standard approach that one can employ.

There is another combination with bendamustine that’s also approved. This is bendamustine plus obinutuzumab. This was based on a randomized phase III trial comparing bendamustine/obinutuzumab and bendamustine alone in patients that had rituximab-refractory disease. The eligibility for this trial doesn’t exactly fit this patient because those patients have rituximab-refractory disease. However, the label allows patients that have had prior chemotherapy and rituximab. So, that would yet be another option for this patient.

For this patient, unfortunately, he’s had a short remission now after second-line therapy with bendamustine/rituximab, and the options become more limited. There is 1 agent that’s approved for this situation: idelalisib. This is a PI3K inhibitor, an oral agent. So, that would be a very reasonable on-label approach. There are clinical trials, again, that I would consider for this gentleman. He’s 66 years old. He would likely be an autologous transplant candidate if he wanted to be aggressive and had chemotherapy-responsive disease, but this is someone who we really need to think of new options for.

As I mentioned, idelalisib is approved for this indication for patients with relapsed follicular lymphoma or small lymphocytic lymphoma who had 2 prior therapies. And this is based on a single-arm phase II trial for patients that had double-refractory disease—disease that was defined as refractory to both an alkylating agent and to rituximab. This patient really would fit that category as well. This was a trial of 125 patients with a variety of indolent B cell lymphoma histologies. The majority had follicular lymphoma. The overall response rate was a primary endpoint, and this was a 57% overall response rate. The duration of response was about 12.5 months and the progression-free survival for the entire cohort was about 11 months. This led to the accelerated approval of idelalisib for this setting.

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.