The Effect of Bortezomib on Renal Dysfunction in African American Patients with Multiple Myeloma

Introduction -

Renal dysfunction (RD) is a major negative prognostic factor in multiple myeloma (MM). Approximately 50% of patients have RD throughout the course of their disease, which is associated with a more aggressive clinical course, poorer quality of life, and shortened overall survival. Bortezomib, a potent proteasome inhibitor, has shown significant anti-myeloma activity and is known to have a protective renal effect. In addition, it is well known that African Americans (AA) are twice as likely to be diagnosed with MM compared to Caucasians and tend to have worse outcomes. At our cancer center, which is in a large urban hospital, nearly 85% of MM patients are AA. To date, there has been no study specifically looking at the reversibility of RD in this population. We evaluated the effectiveness of bortezomib on RD in AA patients with MM in a large urban hospital.

Methods -

We conducted a retrospective analysis to investigate the outcome of bortezomib based therapy in 51 AA patients diagnosed with MM and RD from 2004-2015, including 4 cases requiring hemodialysis. Renal dysfunction was defined as Cr ³ 2.0 mg/dL or GFR < 60 mL/min/1.73m². Patients required at least 3-6 months of continuous treatment with a bortezomib based regimen to be eligible for analysis. Laboratory data was collected prior to initiation of treatment, and again at 3 months and 6 months. Both newly diagnosed and relapsed or refractory patients were included.

Results -

Approximately 75% of patients treated with bortezomib were > 65 years old, with an equal distribution of males and females. At presentation, 80% had anemia (Hb<10 g/dL), 14% hypercalcemia (Ca>11 mg/dL), 37% elevated LDH, 61% elevated B2 microglobulin. The majority of patients had normal risk cytogenetics and 33% were ISS stage III. Myeloma subtype was IgM 65%, IgA 16%, IgM 2%, light chain only 16%. Sixty percent were kappa light chain subtype. The median M spike was 2.54 (range 0.5-16), creatinine 2.41 mg/dL (range 1.1-10.48), GFR 38 mL/min/1.73² (range 6-60). Treatment was bortezomib based in 100% patients: 6% had bortezomib, 45% bortezomib/dexamethasone (VD), 22% VD/cyclophosphamide (VCD), 12% VD/lenalidomide (VRD), 12% VD/melphalan (VMP), 2% VD/thalidomide (VTD), 2% VD/doxorubicin (PAD). A partial response or better was seen in 55% of patients by month 3 and 63% of patients by month 6.

Improvement of RD was observed in 85% of patients by month 3. The average creatinine improved by approximately 24.5% (p<0.001), GFR improved by 52.6% (p<0.001). A plateau effect was noticed by month 6, as creatinine and GFR improved by 19.5% and 44.7%, respectively. Newly diagnosed patients had a greater reversal of RD compared to relapsed/refractory disease (p=0.032). None of the 4 patients who began hemodialysis were able to discontinue this therapy.

Conclusion -

A statistically significant improvement in RD was observed in AA patients with MM based on Cr and GFR treated with a bortezomib based regimen. The greatest response was seen in the first 3 months of therapy which plateaued by month 6. These differences were magnified in de novo compared to relapsed/refractory disease. No patients were able to discontinue hemodialysis if already initiated prior to starting treatment. Bortezomib is a safe and effective drug in the subset of AA patients with impaired renal function.

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