Which induction therapy regimens are used for primary therapy in patients with multiple myeloma who are transplant candidates?

Updated: Dec 31, 2018
  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Patients who present with active (symptomatic) multiple myeloma are treated with induction therapy. [3] Any one of the combination regimens below, most of them based on bortezomib, may be used for induction therapy.

Bortezomib/cyclophosphamide/dexamethasone

This combination may be used in any of the following regimens:

  • Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  cyclophosphamide 300 mg/m2/day PO on days 1, 8, 15, and 22 plus  dexamethasone 40 mg PO daily on days 1-4, 9-12, and 17-20; 28-d cycle for three or four cycles [4, 5, 6]

  • Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  cyclophosphamide 500 mg/m2/day PO on days 1, 8, and 15 plus  dexamethasone 40 mg PO daily on days 1, 8, and 15; 21-d cycle for three or four cycles [4, 5, 6]

  • Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  cyclophosphamide 900 mg/m2 IV over 1 h on day 1 plus  dexamethasone 40 mg PO daily on days 1 2, 4, 5, 8, 9, 11, and 12; 21-d cycle for three or four cycles [4, 5, 6] or

Bortezomib/dexamethasone

Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  dexamethasone 40 mg PO on days 1-4 and days 9-12 (cycles 1 and 2), then 40 mg PO on days 1-4 (cycles 3 and 4); 21-d cycle for three or four cycles [7, 8]

Bortezomib/doxorubicin/dexamethasone

Either of the following two regimens may be used:

  • Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  doxorubicin 9 mg/m2 IV push on days 1-4 plus  dexamethasone 40 mg PO daily on days 1-4, 8-11, and 15-18 (cycle 1), then days 1-4 (cycles two-four); 21-d cycle for three or four cycles [9, 10]

  • Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  doxorubicin 9 mg/m2 continuous IV infusion over 24 h daily on days 1-4 plus  dexamethasone 40 mg PO daily on days 1-4, 9-12, and 17-10; 28-d cycle for three or four cycles [9, 10] or

Bortezomib/lenalidomide/dexamethasone

Bortezomib 1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  lenalidomide 25 mg PO daily on days 1-14 plus  dexamethasone 20 mg PO daily on days 1, 2, 4, 5, 8, 9, 11, and 12 or 40 mg PO daily on days 1, 8, and 15; 21d cycle for three or four cycles [11, 12]

Bortezomib/thalidomide/dexamethasone

Bortezomib 1-1.3 mg/m2 IVP on days 1, 4, 8, and 11 plus  thalidomide 50-200 mg (titrate to tolerance) PO daily at bedtime on days 1-21 plus  dexamethasone 40 mg PO daily on days 1, 2, 4, 5, 8, 9, 11, and 12 or  40 mg on days 1-4 and 9-12 or 40 mg on days 1-4 and 8-11; 21d cycle for three or four cycles [13, 14]

Lenalidomide/dexamethasone

Either of the following two regimens may be used:

  • Lenalidomide 25 mg PO daily on days 1-21 plus  dexamethasone 40 mg PO daily on days 1, 8, 15, and 22 or 40 mg PO daily on days 1-4, 9-12, and 17-20; 28-d cycle for three or four cycles [15, 16]

  • Lenalidomide 25 mg PO daily on days 1-28 plus  dexamethasone 40 mg PO daily on days 1-4, 9-12, and 17-20; 28-d cycle for three or four cycles [15, 16]

Alternative regimens

Any of the following four regimens may be used:

  • Dexamethasone 40 mg/day for 4 d beginning on days 1, 9, and 17 for the first two cycles and 40 mg/day for 4 d beginning on day 1 for the next 10 cycles [17] ; every 6 wk for 12 cycles

  • Pegylated liposomal doxorubicin 40 mg/m2plus vincristine 1.4 mg/m2 (maximum, 2.0 mg) as an IV infusion on day 1 plus  reduced-dose dexamethasone 40 mg PO on days 1-4 [18]

  • Lenalidomide 25 mg PO on days 1-21 plus  dexamethasone 40 mg daily on days 1-4, 9-12, and 17-20; every 28 d [18]

  • Thalidomide 200 mg PO daily plus  dexamethasone 40 mg PO on days 1-4 and 15-18 on even cycles and on days 1-4 on odd cycles; every 28 d [19]

Once a remission has been achieved, stem cells are harvested via apheresis. This is commonly carried out with the use of high-dose cyclophosphamide with growth factors, although it can be done with stem cells alone. Autologous stem cell transplantation utilizes high-dose melphalan 200 mg/m2 or 140 mg/m2, with total body irradiation as a conditioning regimen. Studies are under way to explore the incorporation of bortezomib in the conditioning regimen. [1, 20]


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