Retrospective Review of the Use of High-Dose Cyclophosphamide, Bortezomib, Doxorubicin, and Dexamethasone for the Treatment of Multiple Myeloma and Plasma Cell Leukemia

Abstract

Background: Multiple myeloma (MM) usually follows a clinical course leading to refractoriness and limited treatment options in advanced stages, which might need bridge therapies to either autologous stem cell transplantation or novel therapies. We report our experience with the high-dose chemotherapy mCBAD (modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone) regimen in newly diagnosed MM (NDMM), relapsed/refractory MM (RRMM), and plasma cell leukemia (PCL) patients.

Patients and methods: We searched our electronic records database for MM patients who received mCBAD from 2010 to 2016 for 28-day cycles of cyclophosphamide 350 mg/m² intravenously (I.V.) twice daily with mesna 400 mg/m² I.V. daily (days 1-4), bortezomib 1.3 mg/m² subcutaneously/I.V. (days 1, 4, 8, 11), doxorubicin 9 mg/m² daily continuous infusion (days 1-4), dexamethasone 40 mg orally daily (on days 1-4, 9-12, 17-20). International Myeloma Working Group (IMWG) criteria were used for response assessment and diagnosis. Descriptive statistics, Fisher exact test, χ², Wilcoxon rank sum, and Kaplan-Meier were used for statistical purposes.

Results: One hundred forty patients met the inclusion criteria. A median of 2 cycles of therapy was administered. The overall response rate was 85% in patients with RRMM (n = 116) and 100% in NDMM (n = 13) and PCL (n = 11) patients. Respective median progression-free survival (mPFS) for NDMM, PCL, and RRMM were 19.61 months (95% confidence interval [CI], 5.26 to not applicable [NA]), 7.56 months (95% CI, 4.7 to NA), and 4.64 months (95% CI, 3.75-6.73). Patients with RRMM who used mCBAD as a bridge to autologous transplant (36.2%) had mPFS (11.48 months; 95% CI, 7.52-15.9 months) compared with those who did not (mPFS: 3.19 months; 95% CI, 2.4-3.75 months). Cytopenias occurred in more than 90% of patients, and febrile neutropenia was noted in 26%. All cases of treatment-related mortality (8%) occurred in patients with RRMM, except for 1 patient with PCL.

Conclusion: mCBAD results in high response rates in myeloma and PCL, however, with high treatment-related mortality. Its use in RRMM should be limited to patients who have immediate need for therapy without other treatment options and who have good performance status (score of 0-1) or NDMM if novel agents are not available depending on practice setting. mCBAD can be a treatment option for patients with PCL.

Keywords: High-risk MM; Multiple myeloma; Newly diagnosed MM; Relapse/refractory MM; mCBAD.

Figure 1.

Study design flow chart. mCBAD: modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone

Figure 2.

Progression free survival outcomes in patients receiving the mCBAD regimens-Kaplan Meier survival curves showing A. Progression free survival (PFS) from the initiation of mCBAD in patients with relapsed refractory multiple myeloma (RRMM) B. PFS in patients with RRMM who underwent subsequent autologous stem cell transplant (ASCT), C. PFS in patients with RRMM who did not undergo ASCT, and D. PFS in patients with newly diagnosed multiple myeloma.