CONSIDERATIONS IN MULTIPLE MYELOMA
Figure. Incidence of peripheral neuropathy in a phase 3 trial comparing SC versus IV bortezomib dosing in relapsed myeloma (N=222).11
60
P=.044
SC bortezomib
53% P=.012
50
IV bortezomib
Patients (%)
41% 40
38%
30
24%
P=.026
20
fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). The rate of treatment-related PN was 12.4%. Our institution was one of the participating centers for clinical trials of carfilzomib prior to its FDA approval. Now, we are able to offer this agent to patients off study, and we make sure to follow the recommended dosing, reconstitution, and administration guidelines to ensure maximum benefit and safety. Although we rarely use carfilzomib in the inpatient setting, we do utilize it in patients who come in for emergent plasmapheresis after failing transplant, administering concomitant IV hydration to prevent tumor lysis syndrome. I think this agent is becoming an important retreatment option in MM.
16%
Conclusion 10
6%
0 Any grade
Grade 2
Grade 3
IV indicates intravenous; SC, subcutaneous.
to insert an IV line, wait time is much shorter, which can potentially improve quality of life.
Although MM remains an incurable disease, retreatment with novel agents is leading to higher response rates, prolonged survival, and better quality of life. An important goal in this setting is the prevention and management of AEs, which allows the cancer care team to maximize dose intensity and provide continuation of therapy. This requires careful consideration of comorbidities and other patient factors, as well as a thorough understanding of the doses, schedules, and modes of administration recommended for available agents. References
How is the recently approved agent carfilzomib being used at your center in the retreatment setting?
On July 20, 2012, the FDA approved carfilzomib, a next-generation proteasome inhibitor, for the treatment of patients with MM who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and who have demonstrated disease progression on or within 60 days of therapy completion. Many patients who have relapsed/refractory MM are being treated with carfilzomib at our institution, given its proven efficacy and good safety profile. In a phase 2 study conducted by Siegel and colleagues, patients received single-agent IV carfilzomib for relapsed/refractory MM; all of these individuals were heavily pretreated.12 Of the evaluable patients in this study, 95% were refractory to their last therapy, and 80% were refractory to both bortezomib and lenalidomide. The treatment regimen was designed as IV carfilzomib 20 mg/m2 (cycle 1) followed by 27 mg/m2 (cycle 2), on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The ORR was 23.7%, median duration of response was 7.8 months, and median overall survival was 15.6 months. Reported AEs included
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1. Sood R, Carloss H, Kerr R, et al. Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib. Am J Hematol. 2009;84:657-660. 2. Berenson JR, Jagannath S, Barlogie B, et al. Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. Cancer. 2005;104:2141-2148. 3. Hrusovsky I, Emmerich B, von Rohr A, et al. Bortezomib retreatment in relapsed multiple myeloma—results from a retrospective multicentre survey in Germany and Switzerland. Oncology. 2010;79:247-254. 4. Richardson PG, Weller E, Jagannath S, et al. Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. J Clin Oncol. 2009;27:5713-5719. 5. Madan S, Lacy MQ, Dispenzieri A, et al. Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma. Blood. 2011;118:1763-1765. 6. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™: Multiple Myeloma. Version 1.2013. http://www.nccn.org. Accessed October 24, 2012. 7. Glade J, Fernandez-Llama P, Bosch F, et al. Renal failure in multiple myeloma presenting features and predictors of outcome in a series of 94 patients from a single institution. Arch Intern Med. 1998;158:1889-1893. 8. Revlimid [package insert]. Summit, NJ: Celgene Corporation; 2012. 9. Velcade [package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc; June 2012. 10. Kyprolis [package insert]. South San Francisco, CA: Onyx Pharmaceuticals; July 2012. 11. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12:431-440. 12. Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120:2817-2825.
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