Monitoring Mantle Cell Lymphoma: PET Scans and MRD

Michael L. Wang, MD:PET/CT scans are a very, very important tool. In the older criteria, the Cheson criteria, we only used CT scans. The CT scan has to see the tumor shrink to less than 1.5 or 1 cm, but the PET scan does not require that. The patient can achieve complete remission with a 3-cm residual mass as long as it is no longer PET-positive. So, a PET scan has the integrity to be in the new Cheson criteria, which is called the Lugano criteria. I think it’s a major step forward in the staging of malignant lymphomas. This is especially true for mantle cell lymphoma. It really guides our therapy. So, if you have a patient who got therapy, you have to use a PET scan. If they have a complete metabolic response, you can gauge your therapy towards that. A PET scan is very important. It is an irreplaceable tool to treat mantle cell lymphoma.

MRD to many people is just a simple idea, but there are many scientific extensions into MRD. So, what is MRD? Minimal residual disease. Let me give you an example. People always said this is a very common idea: you treat the patient and the scans or bone marrow biopsy, the common routine for receding criteria, have already yielded a complete remission. Then you check the MRD, either by flow cytometry or by sequencing data, and you find there is disease left. This means you’d still find residual disease, which means you did not get rid of the root of the iceberg. So, MRD is a very common idea, but it is underutilized, which means we have not used MRD adequately. Let me give you an example. If you treat mantle cell lymphoma, the quickest way to restage mantle cell lymphoma is after 2 months. We have to wait for 2 months to do another scan. Let’s say this mantle cell lymphoma is blastoid, very aggressive. It may not respond to the frontline therapy that well. You start with bendamustine/Rituxan [rituximab] and after 1 cycle, you do a PET/CT scan. The tumor already grew, so you have to change the therapy to hyper-CVAD.

However, our national guidelines do not allow you to do a PET scan within 60 days. It is also too much radiation or not convenient to do scans every 2 weeks or every month, and our economy cannot support that. The patient’s body cannot take that amount of radiation. But, if you are able to use the blood test, you can see MRD coming down very nicely. It means your chemotherapy is working; you should continue. And if their MRD goes up, we need to change the chemotherapy. So, MRD not only can tell you the prognosis of the patient after finishing therapy, but it can also actually provide an opportunity to intervene in giving therapy.

MRD is also a technology for early detection. In the future, the science fiction is that we will look at the tumor tissue for diagnosis. In the future, with MRD sophistication coupled with big data, we may be able to detect cancer before it forms a tumor. The whole oncology world will change at that time. Whenever you do not have to deal with a lot of tumors—whether they are initially diagnosed, they’re undergoing therapy, or they’ve completed therapy—you can use much less therapy to get rid of the MRD, so that patient will easily get into remission without a lot of toxicities. So, MRD is exciting. It is one of the major directions of oncology.

Transcript edited for clarity.

March 2013

• A 55-year-old male presents to his physician complaining of fatigue, unexplained weight loss, and neck swelling
• PMH: unremarkable
• Physical exam:
  • Bilateral cervical lymphadenopathy
• Laboratory findings:
  • Leukocytes, 9.0 X 10⁹/L
  • Hb, 9.8 g/dL
  • LDH, 520 U/L
  • Beta2-microglobulin; 6.4 mg/L
  • AST, 167 U/L; ALT 202 U/L
• Excisional biopsy of the right cervical node:
  • Immunophenotyping: IgM+, CD5+, CD10-, CD19+, CD20+, CD22+, CD23-, cyclin D1+
  • Cytogenetics: t(11;14)(q13;q32)
• CT imaging of the neck, chest, abdomen, pelvis: marked¹⁸F-FDG uptake and enlargement of bilateral cervical lymph nodes (right, 4.6 cm; left, 3.1 cm) and mesenteric lymph node (9.2 cm)
• Diagnosis: Mantle-cell lymphoma, Ann Arbor stage III
• The patient was started on induction therapy with R-hyper-CVAD and achieved significant reduction in tumor burden
• Consolidation with autologous stem cell transplant resulted in complete remission

March 2017

• The patient reports having symptoms of fatigue and weight loss
• PET/CT shows diffuse uptake of¹⁸F-FDG in the right lung and mediastinal lymph nodes
• The patient was started on therapy with ibrutinib