Carfilzomib/pomalidomide single-agent or in combination with other agents for the management of relapsed/refractory multiple myeloma: A meta-analysis of 37 trials

Oncotarget

Volumn 8, Issue 24, 2017, Pages 39805-39817

  Zou, Yandun ^a   Ma, Xiaoyan ^b   Yu, Haiying ^b   Hu, Chunling ^a   Fan, Limei ^a   Ran, Xuehong ^b  

^a GUANGDONG WOMEN AND CHILDREN HOSPITAL   (China)

^b WEIFANG PEOPLE'S HOSPITAL   (China)

Author keywords

Bortezomib; Carfilzomib; Lenalidomide; Multiple myeloma; Pomalidomide

Indexed keywords

BORTEZOMIB; CARFILZOMIB; CLARITHROMYCIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; LENALIDOMIDE; OPROZOMIB; PANOBINOSTAT; POMALIDOMIDE; PREDNISONE; VORINOSTAT; ANTINEOPLASTIC AGENT; OLIGOPEPTIDE; THALIDOMIDE;

ACUTE KIDNEY FAILURE; ANEMIA; CANCER RECURRENCE; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; FEVER; HUMAN; LOW DRUG DOSE; META ANALYSIS; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PNEUMONIA; PROGRESSION FREE SURVIVAL; PROSPECTIVE STUDY; REVIEW; SYSTEMATIC REVIEW; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE; VOMITING; DISEASE MANAGEMENT; DRUG RESISTANCE; PATHOLOGY; SALVAGE THERAPY; TUMOR RECURRENCE;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE MANAGEMENT; DRUG RESISTANCE, NEOPLASM; HUMANS; MULTIPLE MYELOMA; NEOPLASM RECURRENCE, LOCAL; OLIGOPEPTIDES; PROSPECTIVE STUDIES; SALVAGE THERAPY; THALIDOMIDE;

EID: 85020665859     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.10768     Document Type: Review

References (47)

1. Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J, Haessler J, Feather J, Hoering A, Moreau P, LeLeu X, Hulin C, Klein SK, et al. Risk of progression and survival in multiple myeloma relapsing after with IMiDs and bortezomib: A multicenter international myeloma working group study. Leukemia. 2012;26(1):149-157
2. Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV, Fonseca R, Witzig TE, Lust JA, Larson DR, Kyle RA, Greipp PR. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867-874
3. Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J, Sullivan D, Alsina M, Schlossman R, Ghobrial IM, Doss D, Loughney N, McBride L,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 Mar 14;121(11):1961-7
4. Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32
5. Rychack E, Mendy D, Miller K. Overcoming resistance; the use of pomalidomide (POM) and dexamethasone (DEX) in re-sensitizing lenalidomide (LEN)-resistant multiple myeloma (MM) cells. Haematologica. 2011;96(Suppl 1):S126. Abstract P-328
6. San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, et al. Pomalidomide plus lowdose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-66
7. Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, 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 Sep 15;118(11):2970-5
8. Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, et al.Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010 Nov;24(11):1934-9
9. Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, Mathiot C, Petillon MO, Macro M, Roussel M, Pegourie B, Kolb B, Stoppa AM, 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 Mar 14;121(11):1968-75
10. Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Kyle RA, Fonseca R, Bergsagel PL, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma.J Clin Oncol. 2009 Oct 20;27(30):5008-14
11. Leleu X, Karlin L, Macro M, Hulin C, Garderet L, Roussel M, Arnulf B, Pegourie B, Kolb B, Stoppa AM, Brechiniac S, Marit G, Thielemans B, et al.Pomalidomide plus lowdose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results. Blood. 2015 Feb 26;125(9):1411-7
12. Matsue K, Iwasaki H, Chou T, Tobinai K, Sunami K, Ogawa Y, Kurihara M, Midorikawa S, Zaki M, Doerr T, Iida S.Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma.Cancer Sci. 2015 Nov;106(11):1561-7
13. Baz RC, Martin TG, Lin HY, Zhao X, Shain KH, Cho HJ, Wolf JL, Mahindra A, Chari A, Sullivan DM, Nardelli LA, Lau K, Alsina M, et al. Randomized multicenter phase II study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma.Blood. 2016 Mar 1
14. Shah J, Niesvizky R, Stadtmauer E, Rifkin RM, Berenson J,Berdeja JG, Sharman JP,Lyons R, Klippel Z, Wong H, Chang YH, Usmani S.Oprozomib, Pomalidomide, and Dexamethasone (OPomd) in Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): Initial Results of a Phase 1b Study (NCT01999335).Blood.Dec, 2015;126 (23)
15. Tomer M, Melissa R, Manan S,Ryann Q,Jessica C, Ramsey A. ClaPD (Clarithromycin/[Biaxin®], Pomalidomide, Dexamethasone) Therapy in Relapsed or Refractory Multiple Myeloma.Blood. Nov 2012
16. Tomer M Mark, Angelique Boyer, Adriana C Rossi, Dennis Kwon,Roger N Pearse, Faiza Zafar, Karen Pekle, Linda Tegnestam, David Jayabalan, Scott A Ely, Morton Coleman,Selina Chen-Kiang, Ruben Niesvizky. ClaPD (clarithromycin, pomalidomide, dexamethasone) therapy in relapsed or refractory multiple myeloma. Blood 2013; 122:1940
17. Jatin J. Shah, Edward A. Stadtmauer, Rafat Abonour, Adam D Cohen, William I. Bensinger, Cristina Gasparetto, Jonathan L. Kaufman, Suzanne Lentzsch, Dan T. Vogl, Robert Z. Orlowski, Erica L. Kim, Marti B. McKinley, Brian G M Durie. A Multi-Center Phase II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma. Blood. 2012, 120(21)
18. Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-90
19. Jatin J. Shah, Edward A. Stadtmauer, Rafat Abonour, Adam D. Cohen, William Bensinger, Cristina Gasparetto, Jonathan L. Kaufman, Suzanne Lentzsch, Dan T. Vogl, Robert Z. Orlowski, Erica L. Kim, Natalia Bialas,David D. Smith, et al. Phase I/II dose expansion of a multicenter trial of carfilzomib and pomalidomide with dexamethasone (Ca-Pom-d) in patients with relapsed/refractory multiple myeloma. Blood 2013; 122:690
20. Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, et al. Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study.Blood. 2013 Oct 17;122(16):2799-806
21. MQ Lacy, B LaPlant, P Richardson, A Jakubowiak, K Laumann, S Kumar, MA Gertz, SR Hayman, F Buadi, A Dispenzieri, JA Lust, PKapoor, N Leung,et al. Pomalidomide, Bortezomib and Dexamethasone (PVD) for Patients with Relapsed Lenalidomide Refractory Multiple Myeloma (MM).Blood, 2014, 124
22. Joseph R. Mikhael, Vivek Roy, Paul G. Richardson, Andrzej Jakubowiak, Kristina Laumann,Betsy R. LaPlant, Angela Dispenzieri, S. Vincent Rajkumar, Rafael Fonseca, Nelson Leung, Francis Buadi, P. Leif Bergsagel, Robert Kyle, et al. A phase I/II trial of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood 2013; 122:1940
23. Paul G. Richardson, Craig C. Hofmeister, David Siegel, Sagar Lonial, Jacob P. Laubach, Yvonne A. Efebera, David H. Vesole, Ajay K. Nooka, Jacalyn Rosenblatt, Noopur Raje, Mohamed H. Zaki, Ye Hua, Yan Li, Sheetal Shah, et al. MM-005: A Phase 1 Trial Of Pomalidomide, Bortezomib, and Low-Dose Dexamethasone (PVD) In Relapsed and/Or Refractory Multiple Myeloma (RRMM). Blood.2013. 122 (21)
24. Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, McDonagh K, Bahlis N, Belch A, Kunkel LA, Wear S, Wong AF, Wang M. An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib.Br J Haematol. 2012 Sep;158(6):739-48
25. Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, et al. An openlabel, single-arm, phase 2 (PX-171-004) study of singleagent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma.Blood. 2012 Jun 14;119(24):5661-70
26. Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma.Blood. 2012 Oct 4;120(14):2817-25
27. Jagannath S, Vij R, Stewart AK, Trudel S, Jakubowiak AJ, Reiman T, Somlo G, Bahlis N, Lonial S, Kunkel LA, Wong A, Orlowski RZ, Siegel DS. An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, singleagent carfilzomib in patients with relapsed and refractory multiple myeloma.Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):310-8
28. Jakubowiak AJ, Siegel DS, Martin T, Wang M, Vij R, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, et al.Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study. Leukemia. 2013 Dec;27(12):2351-6
29. Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, Lee S, Wong AF, Niesvizky R. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety.Leukemia. 2013 Aug;27(8):1707-14
30. Papadopoulos KP, Siegel DS, Vesole DH, Lee P, Rosen ST, Zojwalla N, Holahan JR, Lee S, Wang Z, Badros A. Phase I study of 30-minute infusion of carfilzomib as single agent or in combination with low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma.J Clin Oncol. 2015 Mar 1;33(7):732-9
31. Hájek R1, Bryce R, Ro S, Klencke B, Ludwig H. A study of carfilzomib vs. best supportive care in subjects with relapsed and refractory multiple myeloma (FOCUS). ClinicalTrials.gov. Available at: http://clinicaltrials.gov/show/NCT01302392
32. Lendvai N, Hilden P, Devlin S, Landau H, Hassoun H, Lesokhin AM, Tsakos I, Redling K, Koehne G, Chung DJ, Schaffer WL, Giralt SA. A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma. Blood. 2014 Aug 7;124(6):899-906
33. Berdeja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD, Flinn IW.Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma.Haematologica. 2015 May;100(5):670-6
34. Berenson JR, Hilger JD, Yellin O, Dichmann R, Patel-Donnelly D, Boccia RV, Bessudo A, Stampleman L, Gravenor D, Eshaghian S, Nassir Y, Swift RA, Vescio RA. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy. Leukemia. 2014 Jul;28(7):1529-36. (1)
35. Niesvizky R, Martin TG, Bensinger WI, Alsina M, Siegel DS, Kunkel LA, Wong AF, Lee S, Orlowski RZ, Wang M. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma.Clin Cancer Res. 2013 Apr 15;19(8):2248-56
36. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špicka I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, et al.Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.N Engl J Med. 2015 Jan 8;372(2):142-52
37. Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R.Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood. 2013 Oct 31;122(18):3122-8
38. James R. Berenson, Leonard Klein, Robert M. Rifkin, Priti Patel, MD, Sandra Dixon, Ying Ou, Alan Cartmell. Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma. J Clin Oncol 2014;32:Suppl:8594.abstract. (2)
39. Meletios A. Dimopoulos, Philippe Moreau, Antonio Palumbo, Douglas E Joshua, Ludek Pour, Roman Hajek, Thierry Facon, Heinz Ludwig, Albert Oriol, Hartmut Goldschmidt, Laura Rosinol, Jan Straub, Aleksandr Suvorov, et al. Carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed multiple myeloma (RMM): Results from the phase III study ENDEAVOR.J Clin Oncol 33, 2015 (suppl; abstr 8509)
40. Jonathan L. Kaufman, Todd Zimmerman, Cara A Rosenbaum, Ajay K. Nooka, Leonard T Heffner, R. Donald Harvey, Charise Gleason, Colleen Lewis, Cathy Sharp, Kenisha W Barron, Sagar Lonial. Phase I study of the combination of carfilzomib and panobinostat for patients with relapsed and refractory myeloma: a multicenter MMRC clinical trial [abstract]. Haematologica. 2013;98(suppl 1): Abstract 322
41. Vesole DH, Bilotti E, Richter JR, McNeill A, McBride L, Raucci L, Anand P, Bednarz U, Ivanovski K, Smith J, Batra V, Aleman A, Sims T, et al. Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma.Br J Haematol. 2015 Oct;171(1):52-9
42. Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D.Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102(5): 1115-1123
43. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26): 2609-2617
44. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, et al. International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467-1473
45. Berlin JA, Laird NM, Sacks HS, Chalmers TC. A comparison of statistical methods for combining event rates from clinical trials. Stat Med. 1989 Feb;8(2):141-51
46. Rychack E, Mendy D, Miller K. Overcoming resistance; the use of pomalidomide (POM) and dexamethasone (DEX) in re-sensitizing lenalidomide (LEN)-resistant multiple myeloma (MM) cells. Haematologica. 2011;96(Suppl 1):S126. Abstract P-328
47. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, Munshi NC, Treon SP, Anderson KC. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99(12):4525-4530