Approach to High-Risk Follicular Lymphoma - Episode 4

High-Risk Follicular Lymphoma: Approaching Treatment

March 15, 2018

Ajay K. Gopal, MD:We’re now at 5 months later with this patient who had received 2 cycles of R-CHOP and achieved a partial remission, and this patient now presents with abdominal fullness consistent with, again, progressive disease. You do a physical exam on the patient. This patient now has marked splenomegaly and thrombocytopenia. PET/CT scan shows progressive disease. And at this point, the patient actually gets a repeat biopsy and now comes back as a grade 3 follicular lymphoma. What we don’t know is whether this is a grade 3A or a grade 3B, which is really quite an important distinction. Grade 3B really is a diffuse large B-cell lymphoma, and in the current WHO classification, we would treat this as an aggressive lymphoma. And if that were the case, we would probably, if the patient was fit, give platinum-based chemotherapy, try to get the patient into a remission, and then consolidate with high-dose therapy and autotransplant. It certainly would still be a reasonable option even in a 3A, or even if this was a grade 1/2 follicular. Autotransplant is something we can consider in chemosensitive relapse. So, we don’t really know the situation here, whether this is a grade 3A or a 3B follicular lymphoma.

Another notable point is that this patient developed considerable anemia and thrombocytopenia. If you do a marrow and you see it’s packed with lymphoma, then you have an obvious explanation. However, the patient didn’t tolerate the chemotherapy very well in the past. Patient also had CMV infection. Again, that’s quite unusual at baseline, and you wonder if there’s some underlying marrow disorder with this patient and poor tolerance to chemotherapy. This patient was started on idelalisib therapy, and after about 2 months on therapy developed grade 3 colitis, which was managed. And it sounds like the patient was restarted on therapy based on the case. The patient had stable disease and is remaining on drug at the end of this case.

The question that comes up often is, what are the other choices besides idelalisib in this situation? I want to point out that there is a drug, an historical agent that we can consider maybe not for this patient because they have 90% marrow involvement, but there’s a drug called ibritumomab tiuxetan, which is a Yttrium-90—labeled monoclonal antibody. Commercial name is Zevalin. In those who have less than 25% marrow involvement, we would expect about an 80% response rate. So, that’s actually a really active drug, but you have to use it when the counts are decent and the marrow is not involved. You can’t wait too long to use that drug, but in appropriate patients, that can be quite an effective drug. There’s another PI3-kinase inhibitor called copanlisib, which has recently been approved, same label, 2 prior lines of therapy. This is an IV PI3K inhibitor that is given 3 out of 4 weeks IV. So, it has a very comparable response rate, somewhat slightly different side effect profile, a little bit of hyperglycemia and hypertension following the infusion. And obviously getting an intravenous drug has a different time commitment than an oral agent.

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