POD24 in Follicular Lymphoma

Jeff P. Sharman, MD:There’s a term called POD24, which stands for progression of disease within 24 months, and illustrates or highlights a group of patients who are particularly high risk. They have significantly inferior overall survival relative to their counterparts who don’t have early disease progression. And if anything, it is somewhat of an unmet medical need right now, because these patients are oftentimes going to be the ones who pass away from their disease and behave, frankly, a lot more like a large-cell lymphoma.

There have been some studies that look at repeat biopsy of those individuals in the setting of early progression. And indeed if you progress following bendamustine, rituximab, there’s a greater than 50% chance that you have histologic transformation. It could be even as high as three-quarters of patients. So you’re really in that situation dealing with a different type of lymphoma altogether, which is more of an aggressive large cell lymphoma.

When somebody has an early progression of disease, then it becomes a very different pathway than the one we outlined where you might do lenalidomide, rituximab, or PI3 inhibitors. One of the main questions you would think about in that situation is whether a patient might be suitable for stem-cell transplant. The knowledge base around stem-cell transplants is unfortunately pretty limited. In many cases these were datasets derived before the routine utilization of rituximab, or they’re small studies.

It’s difficult to say definitively that this is the correct approach, but for a patient who did not receive anthracycline therapy in the frontline, you might consider R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. You might consider R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin]. If they had received a prior anthracycline, you might consider R-GDP [rituximab, gemcitabine, cisplatin, dexamethasone]. And for those patients who are both suitable for transplant in terms of fitness and organ function, and have a favorable response to that sort of salvage therapy, autologous stem-cell transplant could be considered.

On the other hand, some patients aren’t going to be suitable for transplant and you’re really working more on a palliative approach at that point to just slow the disease down. And there’s really a fair bit of uncertainty right now for where the role of chimeric antigen receptor T [CAR-T]-cell therapy could fit in this space. I think that’s an area where we’ll see data emerging over the next several years.

Unfortunately, we don’t have tools to prospectively identify who’s going to be an early progressor. In addition to FLIPI [Follicular Lymphoma International Prognostic Index] and FLIPI2, there’s a new thing called the M7-FLIPI that begins to look at some of the molecular details. That’s not necessarily broadly available and there, too, it can be difficult to prospectively utilize these tools to determine who’s going to be an early progressor. So unfortunately, we’re left in the field with early progression being a determination sort of after the fact rather than beforehand. It is probably true that those patients with higher FLIPI might have a higher likelihood of an adverse outcome. That much is reasonable. But there’s not a 1-to-1 prediction there that would link those 2 tightly enough for us to use that as a means to predict who’s going to experience early progression.

Transcript edited for clarity.

Case: A 62-Year-Old Male with Follicular Lymphoma

H & P:

• A 62-year-old man presents with lower abdominal discomfort and rapid weight loss over last 3 months
• PMH: Hypertension managed by statin
• PE: palpable inguinal lymphadenopathy

Diagnostic Work-Up

• Hematologic results
  • ANC: 1200 /µL
  • Platelets: 89,000 /µL
  • β₂-microglobulin: 3.5 mg/L
  • Serum LDH: 230 IU/L
• Imaging: PET/CT reveals axillary and bilateral inguinal lymphadenopathy; 5 masses (~3cm each)
• Biopsy: FL, grade 2
• FLIPI status: High-risk
• Ann Arbor: Stage IV
• ECOG PS: 1

Treatment

• Patient treated with obinutuzumab + bendamustine
  • Completed 6 cycles, achieved CR