Therapy for Relapsed or Refractory MCL

Brad S. Kahl, MD:PET/CT imaging in our patient 3 months after the completion of his induction therapy showed a partial response, and that was shown again at the 6-month mark. So unfortunately, our patient did not achieve a complete response with the BR therapy, which happens in a percentage of patients. With BR induction, I would expect 60% to 70% of patients to go into complete remission, but that means 30% to 40% will achieve no remission at all, or only a partial remission. And we know partial remissions do not last as long as complete remissions, with immunochemotherapy at least. So, we can expect this patient’s remission will not be very durable. In addition, our patient continues to report symptoms of fatigue, and so the decision was made to start him on therapy with ibrutinib.

The question really is, what do you do for a patient who achieves a partial remission? I think ibrutinib is a very reasonable choice here. There are a few other things that could be considered. Maintenance rituximab, perhaps, could flip this patient into a CR. Rituximab given with lenalidomide might be able to flip this patient into a CR. The data for ibrutinib are probably the strongest of all of those options. Ibrutinib is FDA approved for recurrent mantle cell lymphoma. It has an overall response rate of about 60% to 70%, with about 20%, 25% being complete responses.

There are not a lot of data for how well it performs in this exact setting, where you take a patient who has achieved a partial remission and then you put them on ibrutinib therapy. But I would think that ibrutinib therapy would be quite efficacious in this scenario. Ibrutinib is generally well tolerated. Some patients experience diarrhea, myalgias, arthralgias, but those tend to get better with time. We do see some patients experiencing atrial fibrillation. The risk of that appears to be around 5%.

One thing that I’ve noticed with ibrutinib, as I’ve gotten more experience with it over the past few years, is hypertension. And this, in my experience, has been difficult to manage. So, I do think that’s something that has to be monitored in patients on ibrutinib. It’s oral therapy. Patients tend to like that. The dose in mantle cell lymphoma is 560 mg a day. The hope in our patient is that it will convert him into a complete remission, and then we would just keep him on the ibrutinib therapy for as long as we can, as long as it’s tolerated and as long as it’s efficacious. And so, if the patient is tolerating the ibrutinib therapy well and he stays in complete remission, we would continue the ibrutinib therapy in a case like that indefinitely.

Other options for our patient would be to change him to a completely different kind of chemotherapy, like R-CHOP, or add cytarabine or something similar. Certainly, that’s an option, but he just went through 6 months of chemoimmunotherapy and he’s 72 years old, so that’s not highly attractive. Lenalidomide/rituximab is an interesting option. There’s no question that lenalidomide by itself has good single-agent activity in mantle cell lymphoma, and it has an FDA label. The data would suggest that lenalidomide works much better when you combine it with rituximab. So, when I give lenalidomide in instances of mantle cell lymphoma, I always give it with rituximab. They really seem to synergize. That’s a good option, I think, for this patient.

Bortezomib would be another option. Bortezomib is FDA approved for recurrent mantle cell lymphoma. It has good activity. I wouldn’t say it’s great activity, but it’s good. Peripheral neuropathy is the thing you have to watch for the most with bortezomib. Of those 3 options—bortezomib, lenalidomide/rituximab, and ibrutinib—I think ibrutinib is probably the most well tolerated, although it’s a close call with lenalidomide/rituximab. I think any of those 3 would have been reasonable here, but I still think ibrutinib is probably the most attractive choice for our patient.

Transcript edited for clarity.

April 2016

• A 72-year-old male presents to his physician complaining of night sweats, intermittent fever (101°-102°) and fatigue lasting 2 months
• PMH: remarkable for hypertension; controlled on a beta-blocker and diuretic
• Physical exam:
  • Right supraclavicular lymph node, markedly enlarged
  • Spleen, palpable
• Laboratory findings:
  • Leukocytes, 6.73 X 10⁹/L
  • LDH, 420 U/L
• Excisional biopsy of the right supraclavicular node:
  • Immunophenotyping: IgD+, CD5+, CD10+, CD19+, CD20+, CD22+, CD23-, cyclin D1+
  • Cytogenetics: t(11;14)(q13;q32)
  • Bone marrow biopsy confirmed the presence of cyclin D1+ lymphoid cells
• PET-CT: diffuse¹⁸F-FDG uptake in lymph nodes and spleen; the largest involved nodes are the right supraclavicular (4.2 cm), right mesenteric (3.8 cm), and splenic hilar (5.7 cm) nodes
• Diagnosis: Mantle-cell lymphoma, Ann Arbor stage IV
• The patient was started on therapy with bendamustine + rituximab

November 2016

• PET/CT findings at 3 months and 6 months showed a partial response to upfront chemoimmunotherapy
• The patient continues to report symptoms of fatigue
• He was started on therapy with ibrutinib