Treatment Options for FL Progression

Nathan H. Fowler, MD:Thirty-two months later, she presented to the clinic complaining of night sweats and some cervical adenopathy. She had a CT scan, which, again, showed bilateral cervical nodes that were enlarged. She had bilateral axillary nodes along with the hilum node, which was approximately 3.1 cm in diameter. She had a biopsy. One of the cervical nodes in it, again, showed a grade 3a follicular lymphoma very similar to her initial biopsy. She was referred to an academic medical center where she was enrolled in a clinical trial with lenalidomide and rituximab. She received 12 cycles of 12 months of the combination, and she achieved her best response, which was a partial response in the trial.

This patient had a relapse approximately 32 months after receiving bendamustine/rituximab followed by rituximab maintenance for 12 months. This would not be outside of the norm. The median remission times in studies with bendamustine/rituximab are on the order of somewhere between 3 to 5 to 7 years. Now, this patient was a little bit on the short end, 32 months. But, again, I wouldn’t say that in a patient who had a diagnosis of follicular lymphoma at 32 months following induction would be outside of the norm. Why this is relevant? If you see a patient has a very rapid relapse, the first thing you would want to do is rule out any potential transformation.

Now, when a patient presents with relapse, again, beyond 1 year to 2 years after induction therapy, there are several options. In this patient, it has been well over a year since she received rituximab, so one of the options would be to expose her to rituximab as a single agent. There are other drugs that also are very effective in some settings. She could have received rituximab with CDP or potentially rituximab with CHOP chemotherapy as salvage management of this follicular lymphoma.

Transcript edited for clarity.

June 2015

• A 65-year old female presented to her PCP complaining of night sweats and swelling in the neck
• PMH: osteoporosis, neurogenic bladder
• Physical examination:
  • Enlarged spleen 2 cm. below costal margin, bilateral cervical and axillary lymphadenopathy
• ECOG 0
• Laboratory findings:
  • WBC: 12 x 10⁹/L; 45% lymphocytes
  • Hb: 11.5 g/dL
  • Platelets: 213 x 10⁹/L
  • LDH 212 U/L
• Excisional biopsy of the lymph nodes:
  • IHC: CD10+, BCL2+
  • Follicular lymphoma, grade IIIa
• Bone marrow biopsy, 40% involved
• ¹⁸FDG-PET showed SUVmax of 9 with discrete masses bilaterally in the cervical and axillary region and increased uptake in the liver
• FLIPI 4 points, high risk
• The patient was started on bendamustine + rituximab (6 cycles) and was continued on rituximab maintenance therapy for 12 months
• She achieved a partial response with a 75% reduction in tumor volume

February 2018

• After 32 months, the patient complained of her symptoms returning
• CT showed disease progression in the axillary and hilar lymph nodes
• PET with SUV of 11
• Re-biopsy of lymph node, consistent with follicular lymphoma grade IIIa
• The patient was referred to an academic center for treatment
• She was enrolled in an open-label clinical trial of lenalidomide/rituximab (12 cycles)
• She achieved partial remission after 3 months

February 2019

• Twelve months later, the patient presents with low-grade fever and chills, she is otherwise well-appearing and continues to exercise regularly
• ECOG 0
• PET-CT showed further progression in the axillary lymph nodes
• The patient was treated with IV copanlisib and achieved a partial response after 4 cycles; she continues to do well on therapy