Emerging Agents and the Future of Follicular Lymphoma

Ajay Gopal, MD:Nowadays, there are many options for patients with follicular lymphoma, and there are many on the horizon. I think the most important thing is the simple, very important study I mentioned from Carla Casulo showing that those who relapse early—it’s really a common sense finding—tend to have a worse outcome. And I think the most important aspect of this is knowing who we need to be gentle with, and those are the folks who don’t have an early relapse. We really need to minimize toxicity in that 80% of population.

The flip side is those who have an early relapse, like this gentleman in the second case, we really need to talk to them about novel agents, non-traditional chemotherapy approaches, and clinical trials. I mentioned idelalisib, which was approved. There are a number of agents that are in randomized trials. There are some encouraging data using lenalidomide. This is an immunomodulatory drug. Single-arm studies from MD Anderson have shown, in the frontline setting, complete remission rates up to about 90%. A similar patient population or a similar setting from the Nordic study showed, by investigator assessment, only a 36% CR rate. However, these encouraging data with lenalidomide and rituximab have led to a large randomized phase III trial, the so-called RELEVANCE trial, comparing this R2 regimen to investigator’s choice standard chemoimmunotherapy. So, that trial is going to take some time to read out, but this really could be a very important finding to show that we can now get rid of traditional chemotherapy, if it’s positive, and use lenalidomide immunomodulatory therapy plus rituximab.

There are a variety of other strategies that are coming down the pike. There are other B cell receptor pathway agents, such as SIC inhibitors. There are some data with BTK inhibitors. There are antibody drug conjugates such as polatuzumab and vedotin. Chimeric antigen receptor T cells are also looking very encouraging, particularly for those that have very refractory disease. There certainly are anecdotal reports of folks that have had disease that has not responded to anything that are achieving long-term, long-lasting remissions. And finally, there’s allotransplant. Allogeneic transplant is something that’s still on the list for patients that are younger and fitter, and does offer a potentially curative strategy.

In summary, this is actually a very exciting time in terms of novel therapies for follicular lymphoma. Gone are the days of simply giving patients chemotherapy. We have a variety of options targeting various pathways and aspects of both the patient’s tumor and the immunological microenvironment. And, certainly, we hope this will translate into improved long-term outcomes for our patients with follicular lymphoma.

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.