Unmet Needs and Future of R/R Mantle Cell Lymphoma

Kami Maddocks, MD: There are ongoing gaps in the care of mantle cell lymphoma, and there are a few big areas of study. While the BTK inhibitors are very effective, there are still more patients who are going to relapse from their disease. We are trying to prolong these remission durations and deepen the remission durations with single-agent BTK therapy, so there’s a lot of interest going into trials with multiagent, including multiple oral agents. Adding the oral BCL2 inhibitor venetoclax to ibrutinib has shown some promising results. Studies are looking at adding an oral immunomodulator, like lenalidomide, and a number of these different oral BTK inhibitors to really try to prolong and deepen the remission duration.

The other area of interest is in patients with bad prognostic disease: patients with blastoid histology…patients with TP53 mutations who do poorly in general. Even with ibrutinib therapy, patients had either worse progression-free survival or the TP53-mutated patients have worse overall responses. Treating this high-risk population of patients is of high interest. Probably the most exciting ongoing thing in mantle cell right now is results of the recent ZUMA-2 study, which was anti-CD19 chimeric antigen receptor CAR T-cell therapy in relapsed/refractory mantle cell lymphoma patients.

All patients on that trial had been treated with prior BTK therapy, and these had gone up through progression or intolerance to those, and they showed very high response rate. Almost everybody on the trial responded to therapy. Of the 97% overall response rate, 67% of patients exceeded complete remission.

There is toxicity associated with this similar to what there is in large-cell and follicular lymphoma, with neurotoxicity and cytokine release. But there are very promising results, unprecedented results in a population of patients with very poor progression-free survival and overall survival. One of the most exciting things is that we’ll be looking forward to that approval and then CAR T cells that can be even better with less toxicity.

Transcript edited for clarity.

Case: A 76-Year-Old Woman with High Risk Mantle Cell Lymphoma

Initial presentation

• A 76-year-old woman presented with a 2-month history of occasional night sweats, intermittent fatigue and decreased appetite
• PMH: DM, medically controlled; GERD controlled on OTC medication
• PE: bilateral cervical lymphadenopathy, splenomegaly
  
  

Clinical workup

• LDH 405 U/I, ANC 3200/mm3, beta-2-microglobulin 4.1 µg/L, leukocytes, 5.42 X 109/L, hemoglobin 9.1 gm/dL
• FISH: t(11;14)
• Immunocytochemistry: cyclin D1+, CD5+, CD20+, CD43+, CD10-, CD23-
• Bone marrow biopsy positive for lymphoid cells with cyclin D1
• PET/CT scan showed widespread lymphadenopathy including inguinal node (5.1 cm) and splenomegaly
• Ann Arbor stage IV; MIPI score 6.4; ECOG PS 0
  
  

Treatment

• She was started on bendamustine + rituximab
  • Achieved PR
  • Continued on maintenance rituximab q8W
• At 18 months the patient had clinical disease relapse, including an unintentional 7-lb weight loss
  • She was started on ibrutinib 560 mg PO qDay
  • Imaging at 10-week follow-up showed substantial decrease in disease burden