Next Steps in Research in R/R MCL

Javier Munoz, MD, MS, FACP: Mantle cell lymphoma is a rare disease that is incurable at this point, short of an allogeneic stem cell transplant. The CAR [chimeric antigen receptor] T-cell data are not mature enough for us to know long-term durations of response. Of course, we’re going to be collecting that data.

Some variables suggest you’re facing a bad actor when it comes to mantle cell lymphoma, including having a blastoid pathology, a TP53 mutation, high MKI67, relapsed disease quickly after frontline chemotherapy, or progression after a BTK [Bruton tyrosine kinase] inhibitor. I would like to see more combinations of novel agents, both for the frontline setting and for relapsed disease, where we shy away from chemotherapy as much as possible. I would like to see more studies evaluate finite duration of therapy and minimal disease undetectable status. We’re certainly eagerly awaiting data regarding CAR T-cell therapies in mantle cell lymphoma when it comes to other constructs. I would like to see CAR T-cell therapies used earlier, explored as part of clinical trials, and I would like to see trials address the combination of novel agents such as BTK inhibitors or checkpoint inhibitors with CAR T-cell therapies to find that sweet spot where efficacy is increased and toxicity is decreased. With so many options, the future is bright for patients with mantle cell lymphoma.

Transcript edited for clarity.

Case: A 66-Year-Old Woman With Mantle Cell Lymphoma

History

• A 66-year-old woman diagnosed with mantle cell lymphoma in 2017
• She was treated with rituximab, dexamethasone, cytarabine + carboplatin followed by autologous stem cell rescue; achieved PR;
  • Continued on rituximab maintenance therapy
• In 2019 she experienced clinical relapse and was started on acalabrutinib; achieved SD
   

Currently

• She complains of a 3-month history of intermittent fatigue, nausea and dyspnea on exertion
• PMH: DM, medically controlled
• PE: bilateral submandibular lymphadenopathy; otherwise unremarkable
• Labs: WBC 12 X 109/L, hemoglobin 9.8 gm/dL, plt 90,000/u, LDH 410 U/I, ANC 3100/mm3
• Lymph node biopsy: IHC; cyclin D1+, CD10+, CD20+, CD43+; FISH: t (11;14)
• C/A/P CT scan: widespread lymphadenopathy including bilateral submandibular (2.9 cm, 3.4 cm), 2 left-sided axillary lymph nodes (3.7 cm, 4.1 cm), and lumbar region (5.1 cm)
• PET/CT shows diffuse uptake of 18F-FDG in the submandibular, axillary and lumbar lymph nodes
• Beta-2-microglobulin 4.2 µg/L
• Ann Arbor stage IV; MIPI score 6.6, high risk; ECOG PS 0
• Treatment was started with fludarabine + cyclophosphamide, followed by a single infusion of CAR transduced autologous T cell