Jan 19, 2023
ASCO seeks to advance the education of all oncology professionals and ultimately facilitate and support enhanced patient care. The ASCO Oncology Self-Assessment Series on ASCO Connection consists of free case-based multiple-choice practice questions, educational links, and answer rationales from ASCO-SEP.
Learn more about ASCO’s Educational products, such as the 2022 ASCO-SEP Digital Subscription, which includes the digital book, access to education courses and virtual meeting-related content, plus over 1,000 practice questions in the Question Bank. Oncology trainees and training program directors can visit Education Essentials for Oncology Fellows (EEOF) to learn more and register for the 2022-2023 cycle.
Correct answers are listed at the bottom of the page.
Question 1: Leukemia
In her first remission, a 55-year-old woman underwent matched unrelated allogeneic stem cell transplant with myeloablative conditioning for high-risk acute myeloid leukemia (AML). She received antithymocyte globulin (ATG) as a part of conditioning and was placed on cyclosporine and mycophenolate immunosuppression for graft versus host disease (GVHD) prophylaxis. On day 30, she developed mild abdominal discomfort, persistent nausea, and three to four episodes of watery diarrhea per day. Sigmoidoscopy revealed numerous apoptotic bodies in the crypt epithelium. The patient began taking methylprednisolone 2 mg/kg/day to treat acute gastrointestinal GVHD. After 7 days of therapy, there was no improvement in her symptoms.
Which of the following is the most appropriate next step?
- Switch cyclosporine to tacrolimus
Question 2: Multiple Myeloma
A 65-year-old woman with recently diagnosed IgG kappa multiple myeloma presented to the oncology clinic for follow-up. Laboratory results revealed a hemoglobin level of 9.0 g/dL and serum creatinine level of 3.2 mg/dL; her estimated creatinine clearance level was 29 mL/minute. Bone marrow demonstrated 25% plasma cells. There is no evidence of lytic lesions on skeletal survey or PET scan. She is currently on cyclophosphamide, bortezomib, and dexamethasone (CyBorD).
Which of the following therapies is most appropriate to add for this patient?
- Zoledronic acid
- No additional therapy needed
Question 1 Rationale and Reference
Correct answer: C. Ruxolitinib
Rationale: Based on a randomized open-label phase III trial (REACH2 trial) evaluating ruxolitinib versus the best available therapy in patients with steroid-refractory acute GVHD, ruxolitinib therapy led to significant improvements in durable overall response rate at day 56 (40% vs. 22%) with a longer median failure-free survival and overall survival. Based on these results, the FDA approved ruxolitinib for use in patients age 12 and older with steroid-refractory acute GVHD. Other agents listed (infliximab, ATG, and tacrolimus) have not been studied in randomized studies to treat acute GVHD.
- Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute Graft-versus-host disease. N Engl J Med. 2020;382:1800-10. DOI: https://doi.org/10.1056/NEJMoa1917635z.
Question 2 Rationale and References
Correct answer: A. Denosumab
Rationale: All patients beginning myeloma therapy should be started on prophylaxis for skeletal-related events irrespective of bony lesion presence or absence; these patients are at increased risk of developing skeletal-related events. In patients with preexisting renal issues and creatinine clearance less than 30 mL/minute, denosumab is a preferred option. Denosumab is a human monoclonal antibody that binds and inhibits RANK ligand. It is not cleared renally and is shown to be noninferior to bisphosphonate in this setting. Patients on immunomodulatory agents such as lenalidomide are at a higher risk of thrombosis and should be on full-dose aspirin. Bisphosphonates such as zoledronic acid have been the mainstay of therapy; however, bisphosphonate is renally metabolized. In a patient with renal dysfunction, denosumab is a better option.
- Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19:370-81. DOI: https://doi.org/10.1016/S1470-2045(18)30072-X.
- Parrondo RD, Sher T. Prevention of skeletal related events in multiple myeloma: focus on the RANK-L pathway in the treatment of multiple myeloma. Onco Targets Ther. 2019;12:8467-78. DOI: https://doi.org/10.2147/OTT.S192490.