Relapsed Mantle Cell Lymphoma Treatment Landscape

Jonathon Cohen, MD, MS: If you check the NCCN [National Comprehensive Cancer Network] Guidelines, you’ll see that there are a large number of different options available for patients with relapsed mantle cell lymphoma. In the past, patients would be treated with chemotherapy, which may have had moderate effectiveness. Unfortunately, those were often patients who passed away from their disease relatively quickly after the diagnosis of relapsed mantle cell lymphoma. Over the last several years, however, there have been a number of new therapies developed and a number of FDA-approved treatment options for patients. I often will try to use a BTK [Bruton tyrosine kinase] inhibitor in patients with relapsed mantle cell lymphoma at the first time of relapse. There are a number of reasons for whom this may or may not be feasible, but we do know that ibrutinib and other BTK inhibitors are highly effective in this setting. There are, however, a number of other options available, including bortezomib; and lenalidomide is also approved, especially in patients who have relapsed after bortezomib.

Again, there are a number of different therapy options. It really depends on the patient in front of you and their comorbidities and goals. One example may be that a patient may not be interested in continuous therapy. In cases like that, even re-treating a patient with a chemotherapy like bendamustine-rituximab may also be very effective. It really does require an in-depth conversation with a patient, consideration of comorbidities, as well as an evaluation of available treatment options.

The patient in our case received ibrutinib as their initial therapy at the time of relapse. In most cases, this would be my recommendation—to use ibrutinib or 1 of our other FDA-approved BTK inhibitors. We know from a number of different studies that the use of ibrutinib earlier on in the course of treatment tends to be associated with an improved progression-free survival compared with its use later on in the course of treatment. In addition, ibrutinib is generally well tolerated. Although there are some known toxicities that we counsel patients about, most people can be expected to tolerate therapy quite well and remain on treatment for quite some time. Compared with the other available options in the relapsed setting, it tends to compare very favorably.

I think ibrutinib certainly makes sense in this case. Although this patient responded beautifully and had a complete response, that isn’t always the case in patients who receive ibrutinib. In many cases there will be an excellent response, but there still may be some residual adenopathy. This is why we most frequently recommend that patients remain on ibrutinib indefinitely, or at least until they progress or have intolerable toxicity. In most cases, patients are not going to achieve a complete remission. In this case the patient did, and that’s wonderful, and I certainly would recommend that the patient continue on treatment. Hopefully this is 1 of the patients who is going to have a prolonged response to ibrutinib.

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