Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma

M A Dimopoulos, X Leleu, A Palumbo, P Moreau, M Delforge, M Cavo, H Ludwig, G J Morgan, F E Davies, P Sonneveld, S A Schey, S Zweegman, M Hansson, K Weisel, M V Mateos, T Facon, J F S Miguel, M A Dimopoulos, X Leleu, A Palumbo, P Moreau, M Delforge, M Cavo, H Ludwig, G J Morgan, F E Davies, P Sonneveld, S A Schey, S Zweegman, M Hansson, K Weisel, M V Mateos, T Facon, J F S Miguel

Abstract

In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM who have exhausted treatment with lenalidomide and bortezomib. The optimal starting dose of pomalidomide is 4 mg given on days 1-21 of each 28-day cycle, whereas dexamethasone is administered at a dose of 40 mg weekly (reduced to 20 mg for patients aged >75 years). The treatment should continue until evidence of disease progression or unacceptable toxicity. Dose-modification schemes have been established for patients who develop neutropenia, thrombocytopaenia and other grade 3-4 adverse events during pomalidomide therapy. Guidance on the prevention and management of infections and venous thromboembolism is provided, based on the available clinical evidence and the experience of panel members. The use of pomalidomide in special populations, such as patients with advanced age, renal impairment or unfavourable cytogenetic features, is also discussed.

Figures

Figure 1
Figure 1
Treatment algorithm for patients who have failed prior therapy for RRMM. BORT, bortezomib; LEN, lenalidomide; POM/LoDEX, pomalidomide plus low-dose dexamethasone.
Figure 2
Figure 2
Recommended pomalidomide dose modifications for neutropenia. The minimum blood levels required to start treatment with pomalidomide at the full dose of dose 4 mg are ANC ⩾1 × 109/l; platelets ⩾75/109/l or ⩾30 if ⩾50% of bone marrow nucleated cells are plasma cells. It is not recommended to give pomalidomide in doses <1 mg. ANC, absolute neutrophil count; CBC, complete blood count; G-CSF, granulocyte colony-stimulating factor. aFebrile neutropenia is defined as fever ⩾38.5 °C and ANC <1 × 109/l. bG-CSF cycle; 300 μg/kg for 3 days (days 22–24 of each 28-day cycle).
Figure 3
Figure 3
Recommended pomalidomide dose modifications for thrombocytopaenia. The minimum blood levels required to start treatment with pomalidomide at the full dose of dose 4 mg are ANC ⩾1 × 109/l; platelets ⩾75/109/l or ⩾30 if ⩾50% of bone marrow nucleated cells are plasma cells. It is not recommended to give pomalidomide in doses <1 mg. CBC, complete blood count. aConsider frequent platelet transfusions.
Figure 4
Figure 4
Recommendations for determining appropriate thrombosis prophylaxis in patients with RRMM treated with POM/LoDEX. LMWH, low-molecular-weight heparin; POM/LoDEX, pomalidomide plus low-dose dexamethasone; VTE, venous thromboembolism.
Figure 5
Figure 5
Recommended pomalidomide dose modifications for other nonhaematological adverse events.,
Figure 6
Figure 6
Considerations for initiation of pomalidomide plus low-dose dexamethasone therapy. G-CSF, granulocyte colony-stimulating factor; VTE, venous thromboembolism. aPatients >75 years of age should receive dexamethasone 20 mg weekly; younger patients should receive a dose of 40 mg weekly. bG-CSF use may be considered for the first three cycles to prevent neutropenia. cThe recommended starting dose of pomalidomide is 4 mg/day, regardless of the presence of comorbidity. dAntibiotic prophylaxis may be considered for the first three cycles of therapy to reduce the risk of infection. eThromboprophylaxis should be considered for all patients receiving pomalidomide plus low-dose dexamethasone to reduce the risk of VTE.

References

    1. Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26:149–157.
    1. Laubach J, Richardson P, Anderson K. Multiple myeloma. Ann Rev Med. 2011;62:249–264.
    1. Dimopoulos MA, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010;28:4976–4984.
    1. Schütt P, Brandhorst D, Stellberg W, Poser M, Ebeling P, Müller S, et al. Immune parameters in multiple myeloma patients: influence of treatment and correlation with opportunistic infections. Leuk Lymphoma. 2006;47:1570–1582.
    1. Wang X, Ottosson A, Ji C, Feng X, Nordenskjöld M, Henter JI, et al. Proteasome inhibition induces apoptosis in primary human natural killer cells and suppresses NKp46-mediated cytotoxicity. Haematologica. 2009;94:470–478.
    1. Blanco B, Pérez-Simón JA, Sánchez-Abarca LI, Carvajal-Vergara X, Mateos J, Vidriales B, et al. Bortezomib induces selective depletion of alloreactive T lymphocytes and decreases the production of Th1 cytokines. Blood. 2006;107:3575–3583.
    1. Berges C, Haberstock H, Fuchs D, Miltz M, Sadeghi M, Opelz G, et al. Proteasome inhibition suppresses essential immune functions of human CD4+ T cells. Immunology. 2008;124:234–246.
    1. Uy GL, Goyal SD, Fisher NM, Oza AY, Tomasson MH, Stockerl-Goldstein K, et al. Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study. Bone Marrow Transplant. 2009;43:793–800.
    1. Lee SJ, Richardson PG, Sonneveld P, Schuster MW, Irwin D, San Miguel JF, et al. Bortezomib is associated with better health-related quality of life than high-dose dexamethasone in patients with relapsed multiple myeloma: results from the APEX study. Br J Haematol. 2008;143:511–519.
    1. Richardson PG, Delforge M, Beksac M, Wen P, Jongen JL, Sezer O, et al. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia. 2012;26:595–608.
    1. Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79:867–874.
    1. Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009;27:5008–5014.
    1. Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM) Leukemia. 2010;24:1934–1939.
    1. Richardson P, Siegel D, Vij R, Hofmeister C, Baz R, Jagannath S, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study Blood 2014. e-pub ahead of print 13 January 2014 doi:10.1182/blood-2013-11-538835
    1. Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02. Blood. 2013;121:1968–1975.
    1. San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–1066.
    1. European Medicines Agency Imnovid (pomalidomide). Summary of product characteristics. Available from (accessed August 2013).
    1. U.S. Food and Drug Administration POMALYST (pomalidomide). Approved Drugs. Available from (accessed December 2013).
    1. Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24:22–32.
    1. Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23:2210–2221.
    1. Pratt G. Molecular aspects of multiple myeloma. Mol Pathol. 2002;55:273–283.
    1. Stewart AK, Bergsagel PL, Greipp PR, Dispenzieri A, Gertz MA, Hayman SR, et al. A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia. 2007;21:529–534.
    1. Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, Brady HA, Gandhi AK, Schafer PH, et al. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res. 2009;69:7347–7356.
    1. Shaffer AL, Emre NC, Lamy L, Ngo VN, Wright G, Xiao W, et al. IRF4 addiction in multiple myeloma. Nature. 2008;454:226–231.
    1. Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, et al. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007;67:746–755.
    1. Li S, Pal R, Monaghan SA, Schafer P, Ouyang H, Mapara M, et al. IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM. Blood. 2011;117:5157–5165.
    1. De Beneditti A, Graff JR. eIF-4E expression and its role in malignancies and metastases. Oncogene. 2004;23:3189–3199.
    1. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99:4525–4530.
    1. Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy. Blood. 2001;98:2603–2614.
    1. Xu Y, Li J, Ferguson GD, Mercurio F, Khambatta G, Morrison L, et al. Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases. Blood. 2009;114:338–345.
    1. Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999;163:380–386.
    1. Jourdan M, Tarte K, Legouffe E, Brochier J, Rossi JF, Klein B. Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. Eur Cytokine Netw. 1999;10:65–70.
    1. Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 2001;20:4519–4527.
    1. Gupta D, Treon SP, Shima Y, Hideshima T, Podar K, Tai YT, et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia. 2001;15:1950–1961.
    1. Dredge K, Marriott JB, Macdonald CD, Man HW, Chen R, Muller GW, et al. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer. 2002;87:1166–1172.
    1. Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW, et al. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc Res. 2009;77:78–86.
    1. Bolzoni M, Abeltino M, Storti P, Bonomini S, Agnelli L, Todoerti K, et al. The immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and RANKL/OPG ratio in myeloma microenvironment targeting the expression of adhesion molecules Blood (ASH Annu Meet Abstr) 2010116(abstract 448).
    1. Anderson G, Gries M, Kurihara N, Honjo T, Anderson J, Donnenberg V, et al. Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood. 2006;107:3098–3105.
    1. Görgün G, Calabrese E, Soydan E, Hideshima T, Perrone G, Bandi M, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010;116:3227–3237.
    1. Hayashi T, Hideshima T, Akiyama M, Podar K, Yasui H, Raje N, et al. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol. 2005;128:192–203.
    1. Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai YT, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98:210–216.
    1. Reddy N, Hernandez-Ilizaliturri FJ, Deeb G, Roth M, Vaughn M, Knight J, et al. Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol. 2008;140:36–45.
    1. Galustian C, Meyer B, Labarthe MC, Dredge K, Klaschka D, Henry J, et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother. 2009;58:1033–1045.
    1. Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012;26:2326–2335.
    1. Stewart AK.Cereblon is a target of thalidomide, lenalidomide and pomalidomide, predicts clinical outcomes and is mutated in some drug resistant multiple myeloma patients Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract S14-1.
    1. Zhu YX, Braggio E, Shi CX, Bruins LA, Schmidt JE, Van Wier S, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118:4771–4779.
    1. Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood. 2000;96:2943–2950.
    1. Rychak E, Mendy D, Miller K, Schafer P, Chopra R, Daniel TO, et al. Overcoming resistance; the use of pomalidomide (POM) and dexamethasone (DEX) in re-sensitizing lenalidomide (LEN)-resistant multiple myeloma (MM) cells Haematologica (EHA Annu Meet Abstr) 201196(abstract P-328).
    1. Ocio EM, Fernández-Lázaro D, San-Segundo L, Gonazález-Méndez L, Martín-Sánchez M, Garayoa M, et al. Reversibility of the resistance to lenalidomide and pomalidomide and absence of cross-resistance in a murine model of MM Blood (ASH Annu Meet Abstr) 2011118(abstract 134).
    1. Rychak E, Mendy D, Shi T, Ning Y, Leisten J, Raymon H, et al. Pomalidomide and dexamethasone are synergistic in preclinical models of lenalidomide-refractory multiple myeloma (MM) Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract P-294.
    1. Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J, et al. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood. 2013;121:1961–1967.
    1. Vij R, Richardson PG, Siegel DS, Hofmeister CC, Jagannath S, Baz R, et al. Pomalidomide plus low-dose dexamethasone (POM+LoDEX) in RRMM: analyses based on prior therapy and renal function Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract P-170.
    1. Ludwig H, San Miguel JS, Dimopoulos MA, Palumbo A, Garcia Sanz R, Powles R, et al. International Myeloma Working Group recommendations for global myeloma care Leukemia 2013. e-pub ahead of print 1 November 2013 doi:10.1038/leu.2013.293
    1. Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol. 2004;22:3269–3276.
    1. Streetly MJ, Gyertson K, Daniel Y, Zeldis JB, Kazmi M, Schey SA. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol. 2008;141:41–51.
    1. Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011;118:2970–2975.
    1. Lacy MQ, Kumar SK, LaPlant BR, Laumann K, Gertz MA, Hayman SR, et al. Pomalidomide plus low-dose dexamethasone (Pom/Dex) in relapsed myeloma: long term follow up and factors predicting outcome in 345 patients Blood (ASH Annu Meet Abstr) 2012120(abstract 201).
    1. Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–2132.
    1. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–2142.
    1. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–2498.
    1. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11:29–37.
    1. Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Bladé J, Mateos MV, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN) Blood. 2011;118:4519–4529.
    1. Leleu X, Roussel M, Arnulf B, Moreau P, Karlin L, Michallet M, et al. Prolonged overall survival with pomalidomide and dexamethasone in myeloma characterized with end stage disease Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract P-156.
    1. Spencer A.personal communication.
    1. Siegel DS, Richardson PG, Hofmeister C, Vij R, Baz R, Jagannath S, et al. Adverse event management of pomalidomide+low-dose dexamethasone in relapsed and refractory multiple myeloma Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract P-399.
    1. Delforge M, Dimopoulos M, Weisel K, Moreau P, Lacy M, Song K, et al. Adverse events and management in MM-003, a phase 3 study of pomalidomide+low-dose dexamethasone (POM+LODEX) vs high-dose dexamethasone (HIDEX) in relapsed/refractory multiple myeloma (RRMM) Haematologica (EHA Annu Meet Abstr) 201398(Suppl 1)): abstract P788.
    1. Nucci M, Anaissie E. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis. 2009;49:1211–1225.
    1. Mateos MV, García-Sanz R, Colado E, Olazábal J, San-Miguel J. Should prophylactic granulocyte-colony stimulating factor be used in multiple myeloma patients developing neutropenia under lenalidomide-based therapy. Br J Haematol. 2008;140:324–326.
    1. Dimopoulos MA, Palumbo A, Attal M, Beksaç M, Davies FE, Delforge M, et al. Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia. 2011;25:749–760.
    1. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–3205.
    1. Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31:794–810.
    1. Crawford J, Caserta C, Roila F. Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications. Ann Oncol. 2010;21 (Suppl 5:v248–v251.
    1. de Naurois J, Novitzky-Basso I, Gill MJ, Marti FM, Cullen MH, Roila F. Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;21 (Suppl 5:v252–v256.
    1. Longo DL, Fauci AS, Kasper DL, Hause SL, Jameson JL, Loscalzo J.(eds). Plasma cell disorders Harrison's Principles of Internal Medicine18th edn., Part 7, Section 2, Chapter 111McGraw-Hill Education, LLC: Columbus, OH, USA; Available from (accessed 2013).
    1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–1060.
    1. Hoffmann M, Kasserra C, Reyes J, Schafer P, Kosek J, Capone L, et al. Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration. Cancer Chemother Pharmacol. 2013;71:489–501.
    1. Robson RA. The effects of quinolones on xanthine pharmacokinetics. Am J Med. 1992;92 (Suppl 4A:22S–25S.
    1. Stahlmann R, Schwabe R. Safety profile of grepafloxacin compared with other fluoroquinolones. J Antimicrob Chemother. 1997;40 (Suppl A:83–92.
    1. Leleu X, Rodon P, Hulin C, Daley L, Dauriac C, Hacini M, et al. MELISSE, a large multicentric observational study to determine risk factors of venous thromboembolism in patients with multiple myeloma treated with immunomodulatory drugs. Thromb Haemost. 2013;110:844–851.
    1. Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22:414–423.
    1. Zamagni E, Brioli A, Tacchetti P, Zannetti B, Pantani L, Cavo M. Multiple myeloma, venous thromboembolism, and treatment-related risk of thrombosis. Semin Thromb Hemost. 2011;37:209–219.
    1. Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2189–2204.
    1. Kristinsson SY. Thrombosis in multiple myeloma. Hematology Am Soc Hematol Educ Program. 2010;2010:437–444.
    1. Bagratuni T, Kastritis E, Politou M, Roussou M, Kostouros E, Gavriatopoulou M, et al. Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide-based regimens. Am J Hematol. 2013;88:765–770.
    1. Delforge M, Bladé J, Dimopoulos MA, Facon T, Kropff M, Ludwig H, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol. 2010;11:1086–1095.
    1. Geyer HL, Viggiano RW, Lacy MQ, Witzig TE, Leslie KO, Mikhael JR, et al. Acute lung toxicity related to pomalidomide. Chest. 2011;140:529–533.
    1. San Miguel J, Weisel KC, Moreau P, Lacy MQ, Song KW, Delforge M, et al. Quality of life improvements for pomalidomide+low-dose dexamethasone (POM+LoDEX) in relapsed and refractory MM (RRMM) Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract P-430.
    1. European Medicines Agency Revlimid (lenalidomide). Summary of product characteristics. Available from (accessed October 2013).
    1. Matous J, Siegel DSD, Duong HK, Kasserra C, Sternas L, Jacques C, et al. MM-008 trial: pharmacokinetics (PK) and tolerability of pomalidomide plus low-dose dexamethasone (POM plus LoDEX) in relapsed/refractory multiple myeloma (RRMM) patients with renal impairment (RI) J Clin Oncol (ASCO Annu Meet Proc) 201331(Suppl)): abstract 8585.
    1. Siegel DS, Richardson PG, Baz R, Chen M, Zaki M, Anderson KC.Pomalidomide (POM) with low-dose dexamethasone (LoDEX) in patients with relapsed and refractory multiple myeloma (RRMM): impact of renal function on patient outcomes Blood (ASH Annu Meet Abstr) 2012120(abstract 4072).
    1. Weisel KC, Dimopoulos MA, Moreau P, Lacy M, Song KW, Delforge M, et al. Pomalidomide plus low-dose dexamethasone (POM+LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): MM-003 analysis of patients (pts) with moderate renal impairment (RI) J Clin Oncol (ASCO Annu Meet Proc) 201331(Suppl)): abstract 8527.
    1. Weisel K, Dimopoulos M, Moreau P, Lacy M, Song K, Delforge M, et al. Analysis of MM-003 patients with moderate renal impairment using pomalidomide+low-dose dexamethasone (POM+LODEX) vs. high-dose dexamethasone (HIDEX) in relapsed/refractory multiple myeloma (RRMM) Haematologica (EHA Annu Meet Abstr) 201398(Suppl 1)): abstract P244.
    1. Matous J, Siegel D, Duong H, Kasserra C, Sternas L, Jacques C, et al. MM-008: a phase 1 trial evaluating pharmacokinetics and tolerability of pomalidomide+low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) with renal impairment Haematologica (EHA Annu Meet Abstr) 201398(Suppl 1)): abstract P772.
    1. Richardson PG, Lonial S, Jakubowiak A, Baz R, Bahlis N, Siegel DS, et al. Impact of POM+LoDEX on disease parameters and cytogenetic status in relapsed and refractory multiple myeloma (RRMM) Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract O-15.
    1. Dimopoulos MA, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, et al. Final analysis, cytogenetics, long-term treatment, and long-term survival in MM-003, a phase 3 study comparing pomalidomide+low-dose dexamethasone (POM+LoDEX) vs high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM) Blood (ASH Annu Meet Abstr) 2013122(abstract 408).
    1. Leleu X, Karlin L, Macro M, Hulin C, Garderet L, Roussel M, et al. Pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma (RRMM) with deletion (del)17p and/or translocation t(4;14) Blood (ASH Annu Meet Abstr) 2013122abstract 689.
    1. Usmani SZ, Stratton K, Hansen E, Zhang Q, Panozzo SB, Petty NM, et al. Final results of a phase II study of pomalidomide (Pom) in GEP-defined high risk relapsed and refractory multiple myeloma (RRMM) Blood (ASH Annu Meet Abstr) 2013122abstract 3191.
    1. Jagannath S, Hofmeister CC, Baz RC, Siegel DSD, Vij R, Chen C, et al. Pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in patients (Pts) with relapsed and refractory multiple myeloma (RRMM): MM-002 phase II age subgroup analysis J Clin Oncol (ASCO Annu Meet Proc) 201331(Suppl)): abstract 8532.
    1. Jagannath S, Hofmeister C, Baz R, Siegel DS, Vij R, Chen C, et al. The efficacy and safety of pomalidomide with or without low-dose dexamethasone is not impacted by age in patients with advanced relapsed and refractory multiple myeloma: MM-002 subgroup analysis Haematologica (EHA Annu Meet Abstr) 201398(Suppl 1)): abstract P778.
    1. Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, et al. Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study. Blood. 2013;122:2799–2806.
    1. Rossi AC, Mark TM, Rodriguez M, Shah M, Quinn R, Pearse RN, et al. Clarithromycin, pomalidomide, and dexamethasone (ClaPD) in relapsed or refractory multiple myeloma J Clin Oncol (ASCO Annu Meet Proc) 201230(Supplposter): abstract 8036.
    1. Hilger JD, Berenson JR, Klein LM, Bessudo A, Rosen PJ, Eshaghian S, et al. A phase I/II study (NCT01541332) of pomalidomide (POM), dexamethasone (DEX), and pegylated liposomal doxorubicin (PLD) for patients with relapsed/refractory (R/R) multiple myeloma (MM) J Clin Oncol (ASCO Annu Meet Proc) 201331(Suppl)): abstract 8598.
    1. Richardson PGG, Hofmeister CC, Siegel DSD, Lonial S, Laubach J, Efebera YA, et al. MM-005: a phase I trial of pomalidomide, bortezomib, and low-dose dexamethasone (PVD) in relapsed and/or refractory multiple myeloma (RRMM) J Clin Oncol (ASCO Annu Meet Proc) 201331(Suppl)): abstract 8584.
    1. Stadtmauer E, Shah J, Abonour R, Cohen A, Bensinger W, Gasparetto C, et al. Carfilzomib, pomalidomide and dexamethasone (CPomd) for relapsed/refractory multiple myeloma (RRMM): a phase I/II trial Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) 201313(Suppl 1)): abstract P-250.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe