Initiating Therapy for Mantle Cell Lymphoma

Jonathon Cohen, MD, MS: When trying to make a determination about the most appropriate therapy for a newly diagnosed patient, a number of different factors come to mind. Sometimes a patient may be entirely asymptomatic. Regardless of their age or underlying comorbidities, they may be perfectly suitable to be observed without any active therapy. I have patients in my own practice who were diagnosed 4 or 5 years ago and have not had any clinical evidence of progression of disease. We continue to monitor them, and I check on them a couple times a year. This is probably between 6% and 10% of all cases, so it doesn’t happen all the time but is certainly important to keep in mind.

In most other patients, however, you will need to make a decision about therapy fairly early on in the disease course. There are a number of different factors that I at least take into account when making a decision about a patient. In addition to the disease-related characteristics, it’s important to remember the patient in front of you. A patient with multiple comorbidities who is older or frail is not going to be a candidate for real aggressive therapy. On the other hand, the patient who is young and healthy should be considered for very aggressive therapy. Those may be the patients who can enjoy the longest duration of remission.

So there are a number of different factors that come into play, and therapy may range from purely palliative radiation treatment, to a course of single-agent rituximab or other therapies, all the way up to very aggressive combination chemotherapy followed by an autologous stem cell transplant. I think all things being equal, in a patient who does not have a TP53 mutation, who otherwise is eligible for any therapy, I would still favor a cytarabine-based induction regimen followed by stem cell transplantation. However, there are studies underway that are exploring the need for autologous stem cell transplantation, especially if a patient has an excellent response to induction therapy.

When we initiate chemotherapy in patients with mantle cell lymphoma, the goal is to have those patients achieve a complete remission. What we mean by that is have the patient’s PET [positron emission tomography] scan reveal negative disease at the conclusion of therapy. Even though we know that patients are ultimately likely to relapse with this disease, those who achieve a complete remission are likely to stay in remission the longest. So that’s our goal when we start therapy. Although this patient had a good response, the fact that the patient still had a partial remission and not a complete remission would certainly be something that would have me concerned moving forward. In a situation where a patient has responded well but still has some residual disease, one could argue that maintenance rituximab is appropriate to try to prolong remission. But in a patient with clear evidence of residual disease, I start thinking about an alternative therapy pretty early on. Because they tend to relapse fairly quickly, which is what we saw in this case where the patient relapsed in less than a year.

Transcript edited for clarity.

Case: A 68-Year-Old Male with Mantle Cell Lymphoma

Initial presentation

• A 68-year-old man presented with generalized lymphadenopathy, fatigue and an unintentional 8-lb weight loss
• PMH: HTN, medically controlled
• PE: abdominal distention, splenomegaly
  
  

Clinical workup

• LDH 345 U/I, ANC 3500/mm3, beta-2-microglobulin 4.4 µg/L, leukocytes, 5.98 X 109/L, hemoglobin 9.6 gm/dL
• FISH: t (11;14)
• Immunocytochemistry: cyclin D1+, CD5+, CD20++
• BMB positive for lymphoid cells with cyclin D1
• PET/CT scan showed widespread lymphadenopathy in numerous nodal regions including left mesenteric (3.4 cm), bilateral axillary (3.9 cm, 5.3 cm), and cervical (5.1 cm)
• Ann Arbor stage IV; MIPI score 6.3; ECOG PS 1
  
  

Treatment

• Patient was started on bendamustine + rituximab
  • Achieved PR
  • Continued on maintenance rituximab q8W
• At 9 months the patient had clinical disease relapse
  • He was started on ibrutinib 560 mg PO qDay
  • Imaging at 12-week follow-up showed no evidence of disease