Waldenström macroglobulinemia

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Untreated (first-line)

BDR

BDR: Bortezomib, Dexamethasone, Rituximab

Regimen

• Bortezomib (Velcade) 1.3 mg/m2 IV on days 1, 4, 8, 11
• Dexamethasone (Decadron) 40 mg IV on days 1, 4, 8, 11
• Rituximab (Rituxan) 375 mg/m2 IV on day 11

Supportive medications:

• Valacyclovir (Valtrex) 1 gm PO once per day or Acyclovir (Zovirax) 400 mg PO twice per day was recommended for shingles prophylaxis
• "The prophylactic use of plasmapheresis was recommended for patients demonstrating an IgM level of ≥ 5,000 mg/dL before the administration of rituximab, given the potential for rituximab-mediated IgM flare and aggravation of hyperviscosity."

References

1. Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, Willen M, Matous J, Mattern J 2nd, Diener JG, Keogh GP, Myers TJ, Boral A, Birner A, Esseltine DL, Ghobrial IM. Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009 Aug 10;27(23):3830-5. doi: 10.1200/JCO.2008.20.4677. Epub 2009 Jun 8. link to original article contains verified protocol PubMed

Bortezomib and Rituximab

Regimen

• Bortezomib (Velcade) 1.6 mg/m2 IV days 1, 8, 15
• Rituximab (Rituxan) 375 mg/m2 IV on days 1, 8, 15, 22 (cycles 1 and 4, only)

Supportive medications: "Antiviral prophylaxis was recommended in all patients prior to initiation of therapy and for 3 months after completion of the six cycles."

28-day cycles x up to 6 cycles

References

1. Ghobrial IM, Xie W, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Poon T, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia. Am J Hematol. 2010 Sep;85(9):670-4. doi: 10.1002/ajh.21788. link to original article contains verified protocol PubMed

Relapsed/Refractory

Bortezomib and Rituximab

Regimen

• Bortezomib (Velcade) 1.6 mg/m2 IV days 1, 8, 15
• Rituximab (Rituxan) 375 mg/m2 IV on days 1, 8, 15, 22 (cycles 1 and 4, only)

28-day cycles x up to 6 cycles

References

1. Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1422-8. doi: 10.1200/JCO.2009.25.3237. Epub 2010 Feb 8. link to original article contains verified protocol PubMed

Everolimus

Regimen

• Everolimus (Afinitor) 10 mg PO once per day

28-day cycles, given until progression or unacceptable toxicity

References

1. Ghobrial IM, Gertz M, Laplant B, Camoriano J, Hayman S, Lacy M, Chuma S, Harris B, Leduc R, Rourke M, Ansell SM, Deangelo D, Dispenzieri A, Bergsagel L, Reeder C, Anderson KC, Richardson PG, Treon SP, Witzig TE. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1408-14. doi:10.1200/JCO.2009.24.0994. Epub 2010 Feb 8. link to original article contains verified protocol PubMed

Panobinostat

Regimen

• Panobinostat (LBH589) 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)

28-day cycles, given until progression of disease

References

1. Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood. 2013 Feb 21;121(8):1296-303. doi:10.1182/blood-2012-06-439307. Epub 2013 Jan 3. link to original article contains verified protocol PubMed