First-Line Treatment for Mantle Cell Lymphoma

Kami Maddocks, MD: The initial treatment for mantle cell lymphoma is dependent on patient age and comorbidity. In younger patients, we usually use intensive induction therapies. A handful of different regimens have been shown to have similar outcomes, followed by autologous stem cell transplant and then consideration of maintenance with CD20 antibody rituximab.

In patients who are older or not candidates for a more intensive approach, we often use a chemoimmunotherapy approach with rituximab, the CD20 antibody, combined with 1 or more chemotherapies.

The VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone] regimen is a regimen that uses a proteasome inhibitor, bortezomib, in combination with chemotherapy and rituximab in the frontline treatment of mantle cell lymphoma. There is an oral immunomodulator, lenalidomide, which has a small study that looked at it in frontline treatment in combination with rituximab, which may be appropriate for a small subset of patients, although this is not an FDA-approved regimen.

When a patient first presents to you, there are many options for treatment. About 80% of mantle cell lymphoma patients will require treatment at presentation, but about 20% are going to be able to undergo observation. This usually falls within 2 main categories of patients. One would be the patients with leukemic non-nodal disease. They have circulating lymphoma cells, bone marrow, and splenic involvement but not much in the way of lymph node disease.

The other is patients who can be associated with a number of factors, but it is often patients with low tumor burden disease, normal LDH [lactate dehydrogenase], good performance status, and no symptoms from their disease. These patients can be observed without therapy.

The majority of mantle cell is advanced stage at diagnosis, so a combination of chemoimmunotherapy is going to be the most utilized approach. There is a small percentage of…localized disease stage I, where radiation or chemotherapy in combination is an appropriate choice.

Typically, when patients present to me, I look at 2 large things: their age and their performance status. Younger patients who can tolerate more intensive therapy are going to get a more intensive chemotherapy approach, such as the DHAP [dihydroxyacetone phosphate] or the Nordic regimen followed by autologous stem cell transplant. That’s because this has been shown to prolong progression-free survival [PFS], and there’s even been an overall survival benefit shown when rituximab maintenance is used after transplant. You take these patients and put them into significantly longer remission.

Patients who are older or have multiple comorbidities oftentimes are not going to be able to tolerate such an approach, and so outside a clinical trial, they’re looked at as somebody who’s going to use a less intensive chemoimmunotherapy regimen most of the time.

Bendamustine-rituximab is the regimen I utilize in the majority of patients. It has a very high response rate, high complete remission rate, and reasonable progression-free survival. Other chemotherapy options include R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and the VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone] regimen. There are some data on R-BAC [rituximab, bendamustine, cytarabine], which adds a low-dose cytarabine to the bendamustine-rituximab regimen.

Then there is a small study that showed rituximab-lenalidomide in the frontline setting, which induced pretty good remissions with the good 5-year PFS, but this is a small amount. There are emerging data also with the combination of rituximab and the oral BTK inhibitor ibrutinib in the front line. Again, these are not FDA approved therapies at this time.

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