A 77-Year-Old Woman with DLBCL - Episode 8

R/R DLBCL: Treating With Tafasitamab Plus Lenalidomide

September 25, 2020
John M. Burke, MD

John M. Burke, MD: In regard to this particular patient case example, this was an elderly patient who had relapsed 1 year after completing R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] chemotherapy. The options, in theory, would have included stem cell transplant. Right now, CAR [chimeric antigen receptor] T-cell therapy is only approved as a third-line treatment.

Certainly, there are other chemotherapy regimens that could have been chosen here. This patient would have fit into the L-MIND study criteria, having had relapsed disease and because her physician did not feel that she was transplant eligible based on her age and performance status. I think this was a reasonable choice for this patient. You could use it in the second line, or you could use it as third-line therapy or beyond.

One of the questions about this drug is whether it should be used before CAR T-cell therapy. Why? Well, the drug targets CD19. The theoretical concern is that maybe the targeting of CD19 will remove that protein from the cell, and thereby make the CAR T-cell therapy, which is also targeting CD19, ineffective. Of course, you don’t want to do that.

We don’t have a tremendous amount of data on the answer to that question. There are some in vitro data that were presented at ASH [the American Society of Hematology annual meeting] suggesting that removal of CD19 from the cells probably doesn’t happen. That has been looked at in CLL [chronic lymphocytic leukemia] as well. It does not appear that there’s a big reduction in CD19 on the surface of the cell in CLL after tafasitamab exposure. There have been a few case reports, but not a lot, on successful CAR T-cell therapy after tafasitamab. But again, the data are a bit sparse. That’s one of the theoretical concerns about using tafasitamab in the pre-CAR T-cell therapy space. We don’t yet know the answer, and hope that more data forthcoming will help us understand that impact and relationship better.

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