Follicular Lymphoma: Selecting Upfront Therapy

Ajay K. Gopal, MD:One thing we think about is, obviously, which treatment do we choose? There are a number of options, and the first question often is, does the patient need chemoimmunotherapy or immunotherapy alone? This is outside the setting of a clinical trial. So, the question is, do we use rituximab by itself or do we use chemotherapy plus a monoclonal antibody? Typically, when we think of single-agent rituximab use, we think about it in patients who have low tumor burden. Most of us reference the RESORT trial, which had about a 70% response rate to single-agent rituximab; 4 doses of rituximab. It’s important to point out, regarding that trial, that those patients did not, at least based on the publication, have to meet GELF or NCCN criteria for treatment. Many of those patients may have been asymptomatic, so the response rates are probably a bit higher than you might get in symptomatic patients. Typically, when I treat a patient, I look at the burden of the disease. And for those who have high tumor burden, again, outside the setting of a clinical trial, we consider primarily chemoimmunotherapy versus rituximab alone, though patient preference, comorbidities, and other factors certainly come into play.

When we do think about chemoimmunotherapy, the question that often comes up is, which chemotherapy backbone do we use? And the bendamustine/rituximab is often chosen based on 2 prospective clinical trials: first one, the StiL trial and the second one, BRIGHT trial. These were noninferiority trials, and, at least based on the data from those trials, the bendamustine/rituximab appeared to be noninferior to R-CHOP, or R-CHOP/R-CVP in the BRIGHT trial. It’s important to remember that these trials only included grade 1/2 folliculars for those patients who had follicular lymphoma. So, when we talk about somebody with a grade 3 follicular lymphoma, which this patient did not appear to have, at least at this point, we should not apply those data to grade 3 folliculars.

Another interesting regimen that is being evaluated prospectively is the so-called R²regimen, which is lenalidomide (Revlimid) along with rituximab. There were some very provocative single-arm studies that showed this could be a very effective regimen with high response rates and good progression-free survival. For me, I tend to wait. It’s not approved. Lenalidomide is not approved for follicular lymphoma. There can be a challenge getting that paid for, and until the larger RELEVANCE trial fully reads out, which is a randomized phase III trial comparing R²to standard chemoimmunotherapy, I’m typically not using R²off label.

Transcript edited for clarity.

January 2016

• A 62-year-old male presented with left axillary lymphadenopathy
• PMH: DVT managed on warfarin, CMV infection
  • Laboratory findings: CBC count and LDH WNL
  • Excisional biopsy, IHC staining CD10+, grade 2 follicular lymphoma
  • PET/CT, multicompartmental adenopathy and splenomegaly consistent with stage IV disease
  • Bone marrow biopsy, 30% involvement
  • FLIPI 2 (intermediate-risk)
• The patient was started on bendamustine + rituximab (6 cycles)
• She achieved an unconfirmed complete response

June 2017

• 18 months later, he developed recurrent cervical adenopathy with weight loss and fatigue
• Imaging revealed adenopathy in 2 cervical lymph nodes (4.6 cm and 2.4 cm), a mediastinal node (2 cm) and left inguinal node (3.1 cm) with splenomegaly.
• The patient was treated with R-CHOP
• After 2 cycles he developed anemia and grade 2 fatigue
• He achieved a partial response

November 2017

• Five months later, the patient reports feeling tired and abdominal fullness
• Physical exam remarkable for palpable splenomegaly
• Laboratory evaluation showed marked anemia, thrombocytopenia
• PET imaging showed enlargement of pelvic and retroperitoneal nodes and development of several new mediastinal lesions
• Repeat biopsy showed grade 3 follicular lymphoma, 90% bone marrow involvement
• The patient was started on idelalisib therapy
• After 2 months on therapy, he developed grade 3 colitis which was managed
• After four months on therapy, the patient has stable disease