Novel Therapies in Development for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

EP: 1.Case Presentation: A 76-Year-Old Man with Relapsed Diffuse Large B-Cell Lymphoma

EP: 2.First-Line Therapy Options in Diffuse Large B-Cell Lymphoma

EP: 3.Options for Second-Line Treatment in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Now Viewing

EP: 4.Novel Therapies in Development for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

EP: 5.Future Directions for Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Laurie Sehn, MD: What are some of the downsides of this treatment? Of course, there’s no treatment that doesn’t come with some toxicity associated with it. Many of us are familiar with the toxicities of bendamustine and rituximab because it’s a combination we routinely use for many of our patients, particularly those with indolent lymphoma. When you add polatuzumab vedotin to BR [bendamustine, rituximab], there’s a bit of a step up in toxicity. We saw a higher rate of neutropenia associated with the triple combination, although it didn’t translate into a higher risk of infection compared with patients receiving BR [bendamustine, rituximab].

Polatuzumab vedotin can be associated with peripheral neuropathy. Similar to what we see with brentuximab vedotin, there’s a cumulative peripheral neuropathy that can occur. The more treatment patients get, the more likely it is that you may see it in your own patients. Importantly, this is a treatment that’s just based on 6 cycles. With 6 cycles of treatment, for those patients who experience peripheral neuropathy, it was largely low grade and reversible.

What about some other treatment options for this patient? There are other novel therapies in development. The combination of tafasitamab and lenalidomide has also earned FDA approval and is listed in the NCCN [National Comprehensive Cancer Network] Guidelines as an approved therapy for relapsed/refractory DLBCL [diffuse large B-cell lymphoma]. This combination is aiming to induce an immunotherapy with the tafasitamab being an anti-CD19 monoclonal antibody. It’s similar to rituximab, although targeting a different cell surface marker. And then lenalidomide is an immunomodulatory agent. It also likely has some other aspects regarding its mechanism of action. This is a combination that has also shown promise in relapsed/refractory DLBCL and is now accessible as well.

However, in the clinical trial that was performed, patients with primary refractory disease were initially excluded. The majority of patients on the phase 2 trial that earned it its regulatory approval would have had relapsed disease and were perhaps a slightly better-risk group of patients with relapsed/refractory disease. We’ll have to learn as we gain more experience in clinical practice what it might achieve for the primary refractory patient. But for this patient with primary refractory disease who we’ve been discussing, polatuzumab–BR [bendamustine, rituximab] was an excellent option for him as a next step.

This transcript has been edited for clarity.

Case Overview: A 76-Year-Old Man with R/R DLBCL

Initial presentation

• A 76-year-old man presented with progressive fatigue, enlarged lymph nodes in the neck and groin, pruritus and decreased appetite
• PMH: prediabetes, hypertension, medically controlled; BPH; osteoporosis
• PE: palpable cervical and inguinal lymphadenopathy; splenomegaly
• ECOG PS 2
  
  

Clinical workup

• Labs: Hb 9.9 g/dL; all others WNL
• Hepatitis B, C and HIV negative
• Excisional biopsy of the lymph node confirmed DLBCL
• IHC confirmed GCB subtype
• FISH panel: t(14;18) with a BCL2 rearrangement
• Flow cytometry: CD19-postitive
• Whole body PET/CT scan showed FDG avidity in the cervical and inguinal regions, largest node 3.8 cm; splenomegaly
• Ann Arbor stage III DLBCL
• IPI score intermediate-risk age > 60 years, stage 3
• PET scan shows diffuse lymphadenopathy

Treatment

• Treated with R-CHOP x 6 cycles; some dose reductions
• First post-treatment PET/CT scan was markedly improved; CR
• 6 months later there was active relapse of disease
  • Repeat biopsy confirms R/R DLBCL, GCB subtype
• Patient is ineligible for high-dose chemotherapy followed by ASCT based on age and ECOG PS
• Initiated treatment with polatuzumab + bendamustine and rituximab