Plasma cell leukemia

Section editor
	Samuel M. Rubinstein, MD University of North Carolina Chapel Hill, NC, USA LinkedIn

4 regimens on this page 4 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

EMN

• 2018: Gavriatopoulou et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias PubMed

IMWG

• 2012: de Larrea et al. Consensus Statement on Diagnostic Requirements, Response Criteria, and Treatment Recommendations by the International Myeloma Working Group (IMWG) PubMed

First-line therapy

PAD/VCD

PAD/VCD: PS-341 (Bortezomib), Adriamycin liposomal (Pegylated liposomal doxorubicin), Dexamethasone alternating with Velcade (Bortezomib), Cyclophosphamide, Dexamethasone

Regimen

Study	Dates of enrollment	Evidence
Royer et al. 2016	2010-04 to 2013-07	Phase 2

Targeted therapy, both portions (cycles 1 to 4)

• Bortezomib (Velcade) 1.3 mg/m² SC once per day on days 1, 4, 8, 11

Chemotherapy, PAD portion (cycles 1 & 3)

• Pegylated liposomal doxorubicin (Doxil) 30 mg/m² IV once on day 4

Chemotherapy, VCD portion (cycles 2 & 4)

• Cyclophosphamide (Cytoxan) 300 mg/m² PO once per day on days 1 & 8

Glucocorticoid therapy, both portions (cycles 1 to 4)

• Dexamethasone (Decadron) 40 mg PO once per day on days 1, 4, 8, 11

21-day cycle for 4 cycles

Subsequent treatment

• Royer et al. 2016, responding patients: High-dose melphalan & autologous HSCT consolidation

References

1. Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP; IFM. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. link to original article contains dosing details in manuscript PubMed EudraCT 2009-016607-33

Lenalidomide & Dexamethasone (Rd)

Rd: Revlimid (Lenalidomide) & low-dose dexamethasone
RevDex: Revlimid (Lenalidomide) & Dexamethasone
Ld: Lenalidomide & low-dose dexamethasone
LenDex: Lenalidomide & Dexamethasone

Regimen

Study	Dates of enrollment	Evidence
Musto et al. 2013	2009-03-01 to 2011-05-31	Phase 2

Targeted therapy

• Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

Glucocorticoid therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

28-day cycle for 4 cycles

Subsequent treatment

• Musto et al. 2013, responding patients eligible for transplant: HSCT consolidation per center protocol
• Musto et al. 2013, responding patients ineligible for transplant: Rd consolidation x 4 (8 cycles total), then lenalidomide maintenance

References

1. Musto P, Simeon V, Martorelli MC, Petrucci MT, Cascavilla N, Di Raimondo F, Caravita T, Morabito F, Offidani M, Olivieri A, Benevolo G, Mina R, Guariglia R, D'Arena G, Mansueto G, Filardi N, Nobile F, Levi A, Falcone A, Cavalli M, Pietrantuono G, Villani O, Bringhen S, Omedè P, Lerose R, Agnelli L, Todoerti K, Neri A, Boccadoro M, Palumbo A. Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia. Leukemia. 2014 Jan;28(1):222-5. Epub 2013 Aug 20. link to original article contains dosing details in manuscript PubMed

Consolidation after first-line therapy

Melphalan monotherapy, then auto HSCT

Regimen

Study	Dates of enrollment	Evidence
Royer et al. 2016	2010-04 to 2013-07	Phase 2

Preceding treatment

• Upfront PAD alternating with VCD

Chemotherapy

• Melphalan (Alkeran) IV once (day not specified) by the following age- and renal function-based criteria:
  • 65 years old or younger AND CrCl 30 mL/min/1.73m² or more: 200 mg/m²
  • Older than 65 years old OR CrCl less than 30 mL/min/1.73m²: 140 mg/m²

1 or 2 courses

References

1. Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. link to original article contains dosing details in abstract PubMed EudraCT 2009-016607-33

Maintenance after first-line therapy

Lenalidomide monotherapy

Regimen

Study	Dates of enrollment	Evidence
Musto et al. 2013	2009-03-01 to 2011-05-31	Phase 2

Preceding treatment

• Upfront Rd x 8

Targeted therapy

• Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

28-day cycles

References

1. Musto P, Simeon V, Martorelli MC, Petrucci MT, Cascavilla N, Di Raimondo F, Caravita T, Morabito F, Offidani M, Olivieri A, Benevolo G, Mina R, Guariglia R, D'Arena G, Mansueto G, Filardi N, Nobile F, Levi A, Falcone A, Cavalli M, Pietrantuono G, Villani O, Bringhen S, Omedè P, Lerose R, Agnelli L, Todoerti K, Neri A, Boccadoro M, Palumbo A. Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia. Leukemia. 2014 Jan;28(1):222-5. Epub 2013 Aug 20. link to original article contains dosing details in manuscript PubMed