Selected therapies for plasma cell dyscrasias and accompanying renal failure
| Therapy . | Basic mechanism of action . | Regimen and comments . | Citation data . |
|---|---|---|---|
| Bortezomib | Causes apoptosis of immunoglobulin producing plasma cells and interferes with inflammatory pathways which contribute to renal failure. | Dose of 1 to 1.3 mg/m2 on days 1, 4, 8, and 11 for 21 to 28 day cycle, at median of 5 cycles, in combination with dexamethasone, thalidomide, or other agents. Dose does not need adjustment for renal failure. | Jagannath et al,57 Ostermann et al,62 Nozza et al,63 Chanan-Khan et al,58 Ludwig et al,59 Roussou et al,61 and Mohrbacher et al64 |
| Lenalidomide | Inhibits myeloma cell growth and induces apoptosis, interferes with myeloma cell-bone marrow interaction, down-regulates cytokines, up-regulates antimyeloma T-cell activity. | Patients with creatinine > 2.5 mg/dL excluded from phase 3 trials and myelosuppression is more common in renal failure. Use with caution when GFR is reduced, with dose reduction: GFR > 50 mL/min at 25 to 50 mg/day, 30 to 50 mL/min at 10 mg /day, <30 mL/min at 15 mg every other day. Dialysis patients at dose of 15 mg after each dialysis session only. | Dimopoulos et al,67 Niesvizky et al,92 and Borello et al93 |
| Thalidomide | Similar to lenalidomide. Thalidomide may be less potent inducer of apoptosis and T-cell proliferation, but a more potent antiangiogenic agent. | Associated with hyperkalemia in renal failure. Starting dose of 50 to 100 mg/day for GFR < 50 mL/min. | Harris et al68 |
| Dexamethasone | Induces apoptosis of myeloma cells through numerous mechanisms. | High dose necessary at 40 mg on days 1 to 4 and days 9 to 12. Response rates higher when used in combination with other agents. | Kastritis et al66 |
| Autologous SCT | High-dose melphalan conditioning eliminates myeloma cells. | Melphalan dose reduction (140 mg/m2) is required in renal failure and higher treatment related mortality is observed in SCT. Benefits unproven in renal failure. | Sirohi et al,74 Knudsen et al,75 Harousseau et al,76 and Jaccard et al77 |
| Plasmapheresis | Extracorporeal removal of nephrotoxic monoclonal Ig | Standard of care in many cases of IgM paraprotein. Usefulness in IgG-mediated disease remains uncertain. | Cserti et al,81 Clark et al,82 and Leung83 |
| Kidney transplantation | Alternative to dialysis for patients with end-stage renal disease. | Plasma cell dyscrasia must be in complete remission for 3 to 5 years with low and stable monoclonal Ig levels. Paraprotein deposition may recur in allograft. Immunosuppressive medications may increase risk of recurrence or progression of plasma cell dyscrasia. | Leung et al,87 Short et al,88 and Rostaing et al89 |
| Therapy . | Basic mechanism of action . | Regimen and comments . | Citation data . |
|---|---|---|---|
| Bortezomib | Causes apoptosis of immunoglobulin producing plasma cells and interferes with inflammatory pathways which contribute to renal failure. | Dose of 1 to 1.3 mg/m2 on days 1, 4, 8, and 11 for 21 to 28 day cycle, at median of 5 cycles, in combination with dexamethasone, thalidomide, or other agents. Dose does not need adjustment for renal failure. | Jagannath et al,57 Ostermann et al,62 Nozza et al,63 Chanan-Khan et al,58 Ludwig et al,59 Roussou et al,61 and Mohrbacher et al64 |
| Lenalidomide | Inhibits myeloma cell growth and induces apoptosis, interferes with myeloma cell-bone marrow interaction, down-regulates cytokines, up-regulates antimyeloma T-cell activity. | Patients with creatinine > 2.5 mg/dL excluded from phase 3 trials and myelosuppression is more common in renal failure. Use with caution when GFR is reduced, with dose reduction: GFR > 50 mL/min at 25 to 50 mg/day, 30 to 50 mL/min at 10 mg /day, <30 mL/min at 15 mg every other day. Dialysis patients at dose of 15 mg after each dialysis session only. | Dimopoulos et al,67 Niesvizky et al,92 and Borello et al93 |
| Thalidomide | Similar to lenalidomide. Thalidomide may be less potent inducer of apoptosis and T-cell proliferation, but a more potent antiangiogenic agent. | Associated with hyperkalemia in renal failure. Starting dose of 50 to 100 mg/day for GFR < 50 mL/min. | Harris et al68 |
| Dexamethasone | Induces apoptosis of myeloma cells through numerous mechanisms. | High dose necessary at 40 mg on days 1 to 4 and days 9 to 12. Response rates higher when used in combination with other agents. | Kastritis et al66 |
| Autologous SCT | High-dose melphalan conditioning eliminates myeloma cells. | Melphalan dose reduction (140 mg/m2) is required in renal failure and higher treatment related mortality is observed in SCT. Benefits unproven in renal failure. | Sirohi et al,74 Knudsen et al,75 Harousseau et al,76 and Jaccard et al77 |
| Plasmapheresis | Extracorporeal removal of nephrotoxic monoclonal Ig | Standard of care in many cases of IgM paraprotein. Usefulness in IgG-mediated disease remains uncertain. | Cserti et al,81 Clark et al,82 and Leung83 |
| Kidney transplantation | Alternative to dialysis for patients with end-stage renal disease. | Plasma cell dyscrasia must be in complete remission for 3 to 5 years with low and stable monoclonal Ig levels. Paraprotein deposition may recur in allograft. Immunosuppressive medications may increase risk of recurrence or progression of plasma cell dyscrasia. | Leung et al,87 Short et al,88 and Rostaing et al89 |
GFR indicates glomerular filtration rate; and SCT, stem cell transplantation.