Optimal Induction Therapy for Multiple Myeloma

Patients with multiple myeloma tend to have a propensity to form blood clots. The addition of dexamethasone and lenalidomide increases the risk of deep vein thrombosis significantly, and requires some form of antiplatelet or anticoagulation therapy to reduce that risk.¹²

Renal dysfunction may limit the choice of therapy or require the need for dose modifications during treatment. Lenalidomide is commonly used as initial therapy for multiple myeloma and requires dose adjustments as summarized in Table 3.

Table 3. Lenalidomide Dose Adjustment for Renal Impairment for Multiple Myeloma¹³

Category of Renal Dysfunction	Renal Function Clcr mL/min (Crockcroft-Gault)	Dose
Moderate	30-60	10 mg orally every 24 hours
Severe	<30 (not on dialysis)	15 mg orally every 48 hours
End Stage Renal Disease	<30 (on dialysis)	5 mg orally every 24 hours. Doses that fall on dialysis days should be given after dialysis.

Adapted from Revlimid (lenalidomide) Prescribing Information 2011.¹³

Summary
For this patient without comorbidities and only mild renal dysfunction, the optimal induction would probably be lenalidomide, bortezomib, and dexamethasone for four to six cycles and proceed to stem cell transplantation. In summary, the optimal treatment of multiple myeloma today requires a multidisciplinary approach. The advent of novel therapeutic agents has opened new avenues of therapy, which although extremely effective, can be associated with significant toxicities. A team approach to treatment of the multiple myeloma patient goes a long way in reducing the potential for serious complications during induction and consolidation therapy. Appropriate education of caregivers and healthcare providers, particularly regarding symptom recognition and reporting, as well as careful monitoring by the treatment team of physicians, nurses, and pharmacists, are essential to optimize outcomes and reduce complications.

 

References
1. Kyle R.A., Rajkumar S.V. Multiple myeloma. N Engl J Med. 2004:351(18):1860-1873.

2. IMWG response criteria. International Myeloma Foundation website. http://myeloma.org/ArticlePage.action?articleId=2994. Accessed March 26, 2012.

3. National Comprehensive Cancer Network Clinical practice guidelines in oncology: multiple myeloma V.1.2012. National Comprehensive Cancer Network website. http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf. Accessed March 26, 2012.

4. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23(1):3-9.

5. Chanan-Khan A, Giralt S: Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol. 2010;28(15):2612-2624.

6. San-Miguel J.F., Mateos M.V.  How to treat a newly diagnosed young patient with multiple myeloma. Hematology Am Soc Hematol Educ Program. 2009:555-565.

7. Cavo M., Tacchetti P., Patriarca F., et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376(9758):2075-2085.

8. Harousseau J.L., Attal M., Avet-Loiseau H., et al. bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010;28(30):4621-4629.

9. Sonneveld P, Schmidt-Wolf I.G.H., Van der Holt B., et al:HOVON-65/GMMG-HD4. Randomized phase III trial comparing bortezomib, doxorubicin, dexamethasone (PAD) vs VAD followed by high dose melphalan and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma [abstract]. Blood. 2010;116. Abstract 40.

10. Cavo M., Rajkumar S.V., Palumbo A., et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011;117(23):6063-6073.

11. Jagannath S. Treatment of patients with myeloma with comorbid conditions: considerations for the clinician. Clin Lymphoma Myeloma. 2008;8(suppl4):S149-S156.

12. Zamagni E., Brioli A., Tacchetti P., et al. Multiple myeloma, venous thromboembolism, and treatment-related risk of thrombosis. Semin Thromb Hemost. 2011;37(3):209-219.

13. Revlimid [package insert]. Summit, NJ: Celgene Corporation; 2011.