A 77-Year-Old Woman with DLBCL - Episode 5

Current Treatment Approaches for R/R DLBCL

John M. Burke, MD: One important point that I think can get overlooked not infrequently is that not everyone who has a positive PET [positron emission tomography] scan at the end of treatment actually has persistent disease. It’s really important, if a PET scan is positive and the treating physician is concerned about that, to repeat a biopsy to make sure that we are in fact dealing with persistent disease, because that’s not always the case. Some of the best data to support that are from a study called REMARC, where patients were treated with R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] and then randomly assigned to maintenance lenalidomide or observation.

Of the patients on that study who were in a partial remission at the end of induction, meaning they were thought to have residual disease, 29% converted to complete remission with no additional therapy on the observation-alone arm. A number of PET scans that were positive simply became negative with time. Clearly, those patients had abnormal PETs—they were not in a complete remission—but didn’t necessarily ever relapse. Again, I think that proves the point that a lot of these positive PETs do not necessarily reflect persistent disease. So it’s important to do a biopsy if a PET is positive and you’re concerned about this being primary refractory disease. Overall, I think about one-third of patients with large cell lymphoma will eventually relapse after R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] therapy. That progression-free survival of about 60% to 65% means that about one-third of patients are relapsing.

I think you asked, what are the treatment options for patients with relapsed disease? It’s an area right now that’s changing rapidly. We’ve basically had 3 new approvals within the last year, so it’s an exciting time and there’s a lot to talk about here. For most patients, the first thing we do when we see a patient with relapsed large cell lymphoma is ask ourselves whether they’re eligible for autologous stem cell transplant. We think that has the highest likelihood of cure for patients with relapsed large cell lymphoma. If a patient is eligible for a transplant, we will offer them salvage chemotherapy with a regimen such as ICE [ifosfamide, carboplatin, and etoposide] with or without rituximab. Or we could offer DHAP [dexamethasone, high-dose cytarabine, and cisplatin] with or without rituximab. And then if they have chemotherapy-sensitive disease and achieve at least a partial response, we can follow that chemotherapy with high-dose therapy and autologous stem cell transplant. That’s probably the preferred modality for many patients.

There are patients who relapse, who are immediately known to be ineligible for transplant either by age or comorbidities or performance status. Those patients do not have, of course, the option of doing a stem cell transplant. Those patients generally can be treated either with conventional chemotherapy—an example of a regimen might be rituximab plus gemcitabine with or without oxaliplatin—or, as of last year, we have the combination of polatuzumab vedotin plus bendamustine plus rituximab. Now, I say that, and the study of that combination did treat patients in both the second-line setting and third-line setting and beyond, but the FDA approval and NCCN [National Comprehensive Cancer Network] guidelines are written such that patients who are eligible for that treatment regimen should have received at least 2 prior therapies. In both of those cases, it’s listed as a third-line option. However, in my opinion, it can be used as a second-line option for patients known to be transplant ineligible. Again, those patients were included on the study.

We now have a new option for transplant-ineligible patients in the second line, which is the combination of tafasitamab plus lenalidomide. We’ll come to that regimen and will discuss that a little bit more in a minute.

CAR [chimeric antigen receptor] T-cell therapy is the preferred third-line treatment modality right now. For patients who are not eligible for CAR T-cell therapy, they would have the option of a salvage chemotherapy regimen. Again, rituximab plus gemcitabine with or without oxaliplatin is 1 example. Another option is polatuzumab/bendamustine/rituximab. In the third-line setting, that regimen is approved and NCCN recommended. We have tafasitamab plus lenalidomide, again FDA approved and NCCN recommended. We also now have the new drug selinexor approved and available in that space. So, we have many options for third-line therapy and beyond.

Transcript edited for clarity.


Case: A 77-Year-Old Woman With DLBCL

Initial Presentation

  • A 77-year-old woman presented with loss of appetite, fatigue and shortness of breath
  • PMH: post-menopausal; DM, medically controlled
  • PE: palpable inguinal lymphadenopathy; splenomegaly
  • ECOG PS 1

Clinical Work-up

  • Labs: Hb 9.8 g/dL; all others WNL
  • FEV1 45 %
  • Hepatitis B, C and HIV negative
  • Core needle biopsy of the inguinal node: CD20-positive diffuse large B-cell lymphoma, non-GCB subtype. FISH panel: t(14;18) with a BCL2 rearrangement; no MYC or BCL6 rearrangement
  • Imaging:
    • Whole body PET/CT scan showed FDG avidity the inguinal lymph node region, largest node 3.3 cm; splenomegaly; and a small suspicious lung lesion
  • Bone marrow biopsy: involvement with DLBCL
  • Conclusion: stage IV DLBCL, non-GCB subtype
  • IPI score high-risk; CNS relapse score intermediate risk

Treatment

  • Treated with R-CHOP for 6 cycles
  • End-of-treatment PET/CT demonstrates a Deauville 2 complete remission
  • 1 year later while in surveillance she presents with new cervical, axillary, mediastinal, and abdominal lymphadenopathy
  • Core needle biopsy of an axillary node confirms a relapse of DLBCL, non-GCB subtype
  • Based on her age of 78 years and performance status, you consider her to be transplant-ineligible
  • You elect to initiate tafasitamab + lenalidomide