Oncology Self-Study: Multiple Myeloma and Gastrointestinal Cancers

Apr 30, 2019

Test your knowledge of multiple myeloma and gastrointestinal cancers with questions from self-evaluation activities on ASCO University.

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Correct answers are listed at the bottom of the page.

  1. A 61-year-old man with no significant past medical history is admitted for bone pain and progressive fatigue. Laboratory studies are remarkable for hemoglobin of 7.8 g/dL, white blood cell count of 11.1 uL, and platelets of 189,000/uL. Serum creatinine is 6.1 mg/dL and serum protein electrophoresis demonstrates a monoclonal IgG kappa M-protein of 4.2 g/dL. Bone marrow biopsy and aspirate reveals 60 to 70% kappa-restricted plasma cells and cytogenetics and FISH panel are pending.

Which of the following induction regimens would be the most appropriate choice for this patient?

A: Bortezomib, cyclophosphamide, and dexamethasone

B: Bortezomib, lenalidomide, and dexamethasone

C: Lenalidomide and dexamethason

D: Thalidomide and dexamethasone

  1. A 46-year-old white woman presented to her primary care physician with persistent hematochezia and rectal discomfort. The patient has past medical history of hyperlipidemia and 30-pack year history of smoking. Physical exam revealed a 3-cm fungating anal mass at 3 to 6 o’clock position, along with a tender 2-cm palpable left inguinal lymph node. Anoscopy was performed with biopsy. Pathology revealed invasive moderately differentiated squamous cell carcinoma, p16+. Staging evaluation was done including a CT chest and abdomen and MRI pelvis. This confirmed a 3.5-cm mass arising from anal canal without invasion of adjacent organs and a pathologically enlarged left superficial inguinal node. Labs were notable for negative HIV serology and mild microcytic anemia (hemoglobin 11 g/dL, mean corpuscular volume (MCV) 77 fL). The patient went on to receive definitive chemoradiation (5-FU and mitomycin-C). Physical exam at 12 weeks reveals marked improvement in anal mass, however, there was still a 1-cm area of induration. Inguinal lymph node exam revealed complete resolution of previously palpable left inguinal adenopathy. Anoscopy was performed and biopsy of the area of concern reveals invasive squamous cell carcinoma.

What is the most appropriate next step in management?

A: Refer patient to colorectal surgery for abdominoperineal resection (APR)

B: Proceed with palliative chemotherapy

C: Reevaluate the patient in 6 weeks with digital rectal exam, anoscopy, and biopsy

D: Proceed with anti-PD1 therapy

Rationale

1: A

Approximately 20% of patients with multiple myeloma present with renal failure at the time of diagnosis. Several chemotherapy agents used in the treatment of myeloma are safe and effective in renal failure to include proteasome inhibitors such as bortezomib. Renal failure is reversible in about half of these patients and is associated with improved survival. Studies comparing different regimens including bortezomib with cyclophosphamide, lenalidomide-based regimens, and thalidomide-based regimens have shown improved responses and survival with bortezomib-based regimens. Both the NCCN and International Myeloma Working Group list cyclophosphamide, bortezomib, and dexamethasone as a preferred regimen in this setting. Three-drug regimens have better response rates and improved progression-free survival compared with two-drug regimens and are considered standard.  Lenalidomide can be used in renal failure but requires dose reductions has lower response rates than bortezomib. Thalidomide can be given without dose modification, but both have inferior response rates compared with bortezomib.

Suggested Readings

  1. Dimopoulos MA, Roussou M, Gkotzamanidou M, et al. Leukemia, 2013. 27(2):423-9.
  2. Reeder CB1, Reece DE, Kukreti V, et al. Br J Haematol, 2014. 167(4):563-5.

2: C

This patient could very well achieve a complete clinical response in 6 to 12 weeks. In a large study, 64% of patients achieved complete clinical response by 11 weeks and this increased to 85% at 26 weeks. APR would be inappropriate at this time point in a patient who is responding to therapy. Systemic therapies (chemotherapy or immunotherapy) would be inappropriate given that the patient does not have metastatic disease.

Suggested Readings

  1. Glynne-Jones R, Sebag-Montefiore D, Meadows HM, et al. Lancet Oncol, 2017. 18(3):347-356.
  2. James RD, Glynne-Jones R, Meadows HM, et al. Lancet Oncol, 2013. 14(6):516-24.
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