A 77-Year-Old Woman with DLBCL - Episode 9

Progress Made in Treating R/R DLBCL

John M. Burke, MD: We have seen tremendous progress in diffuse large B-cell lymphoma in the last 4 or 5 years, with 2 FDA-approved CAR [chimeric antigen receptor] T-cell products, and perhaps a third to come. Polatuzumab vedotin was approved last year in combination with bendamustine and rituximab. This followed the first randomized trial in relapsed large cell lymphoma in recent memory to improve overall survival. That’s a big deal.

We’ve talked a lot about tafasitamab and lenalidomide today. Selinexor is a recently approved oral drug. This is an inhibitor of exportin 1. In the study, there were lower response rates, but in the high 20% range, and responding patients did pretty well. So that’s a new option for patients. There’s a lot going on, we have a lot of new options.

It’s interesting to think about what the right algorithm is right now. As you asked, how do you sequence these new drugs? I don’t think there’s a right answer right now. A lot of it is going to come down to sitting with an individual patient and thinking through the pros, cons, risks, and benefits with them and making the best decision for that patient. Again, if the patient is transplant eligible, the standard remains using a salvage chemotherapy regimen followed by stem cell transplant. If they are transplant ineligible but your goal is to get them to CAR T-cell therapy, then, I haven’t talked to my CAR-T doctors who I refer to about this, but I suspect they’re going to favor something like rituximab, gemcitabine, oxaliplatin, although tafasitamab, lenalidomide may be reasonable. I know there are concerns about bendamustine pre-CAR T-cell collection, but polatuzumab vedotin with bendamustine, rituximab or polatuzumab vedotin with rituximab without bendamustine could be used. So we have a number of different choices there.

If you feel the patient is not headed toward CAR T-cell therapy because of performance status or comorbidities, the field is wide open. Polatuzumab vedotin, bendamustine, rituximab, tafasitamab, lenalidomide, and selinexor are all available in the third-line setting, plus good old-fashioned chemotherapy.

You can sit down with your patients. I think each of these options has pros and cons to think through. With polatuzumab vedotin, a pro is the survival advantage that was seen in a randomized phase 2 trial. Tafasitamab/lenalidomide has a great response rate and a manageable toxicity profile. One disadvantage of tafasitamab/lenalidomide is that we don’t have a chemotherapy comparator arm. We only have the lenalidomide-alone comparator arm. My understanding is that there are some retrospective data going on with an effort to do a chemotherapy comparator study. So, stay tuned on that.

As third-line therapy, CAR T is preferred if your patients can get to it. Not only does CAR T have excellent response rates, but we’re seeing prolonged disease-free survival in about a third of those patients. There are a lot of complex choices to make, and you have to sit down with your patients and go through some of those pros and cons.

In this era of rapidly changing options for diffuse large B-cell lymphoma, doctors certainly need to familiarize themselves with these new drugs and their risks, benefits, and adverse effects. I think having early discussions with transplanters and CAR T-cell therapy providers to whom you refer patients is really important, if you’re not doing those treatments yourselves. It’s important to get them involved in helping map out how to proceed and get this patient to the best available therapy.

Then, it’s important to move quickly, I think it’s conceivable with all these new options that we can turn this disease into a bit more of a chronic disease than it’s been. In these patients who can’t get transplants or who relapse after transplant, relapsed large cell lymphoma has a terrible prognosis. From retrospective studies, we know the median survival is on the order of months. So, it’s essential that we move quickly, get them on some of these effective treatments soon, and again, have those early conversations with your transplant and CAR T doctors you work with to make sure you make as many of these options available to your patients as you possibly can. That’s going to give your patients the best outcome.

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