76-Year-Old-Woman With Stage IV Mantle Cell Lymphoma

Kami Maddocks, MD: Today we are going to talk about a 76-year-old woman who presented with 2 months of symptoms that included night sweats, fatigue, and weight loss. The patient was relatively healthy, with a past medical history of diabetes controlled on oral medications and reflux controlled on over-the-counter medication. The patient presented with palpable cervical inguinal adenopathy on exam.

Work-up of the patient showed labs consistent with an anemia with a hemoglobin of 9 g/dL, a normal white blood cell count, but an elevated LDH [lactate dehydrogenase] of over 400 U/L. Biopsy showed immunohistochemistry consistent with a positive cyclin D1, CD5, CD20, negative CD10, and FISH [fluorescence in situ hybridization] was positive for translocation 11;14. The patient went on to have staging scans with PET [positron emission tomography] and CT [computed tomography] that showed significant adenopathy above and below the diaphragm, including an over-5-cm inguinal node, and splenomegaly, and bone marrow was positive for the disease.

In summary, this a 76-year-old woman with stage IV mantle cell lymphoma with high-risk MIPI [Mantle Cell Lymphoma International Prognostic Index] score of 6.4, and that ECOG performance status of 0.

The patient went on to receive initial therapy with a combination of bendamustine and rituximab. The patient achieved a partial remission to the 6 cycles of chemotherapy and then went on to receive rituximab maintenance with 1 infusion every 8 weeks.

A year and a half after the patient had started chemotherapy, she presented with increasing symptoms suggested above disease relapse, including further weight loss, and this was confirmed. She was then started on therapy with ibrutinib 560 mg orally daily, and a follow-up 10 weeks later showed a good response to treatment.

We have a 76-year-old woman with B symptom, so she had symptomatic disease, which puts her in the category of needing treatment. Her age puts her in the category of a less intensive chemotherapy approach; she’s not somebody you’re going to be aggressive or consolidate with transplant. She does have bulky disease and had greater than 5-cm lymph node, which are also indications for treatment. She has high-risk disease by the MIPI score, with a less favorable outcome based on that.

Ki-67 had been shown to be prognostic in that it’s a marker of disease turnover or aggressiveness. So Ki-67 of less than 10% has been shown to be favorable in patients regardless of treatment approach. A Ki-67 of greater than 30% has shown to be indicative of more aggressive disease or a worse outcome with the different treatment hosts.

A muscle density is something that’s been reported in other malignancies as being associated with outcomes, and it was shown in 1 mantle cell lymphoma study to be predictive of outcomes. Skeletal muscle density can be suggestive of a patient baseline muscle function, and it can be associated with cytokine release and early cachexia. The randomized phase 3 trial looking at R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] versus VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone] looked at patients’ skeletal muscle density by CT scan before patients were initiated on treatment, and then at certain points of follow-up after treatment.

What they found is that a low skeletal muscle density was associated with worse progression-free survival and overall survival independent of the treatment arm...improvement in...muscle density, and therefore that could improve that patient’s outcome.

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