Pomalidomide in multiple myeloma

Figures & data

Table 1. Pomalidomide phase I and, I and II trials in multiple myeloma.

Authors	Population	No of patients	Schedule	ORR	Median PFS
Phase I tials
Schey et al. [2]	Relapsed/refractory	24	MTD Pom 2 mg 28/28	54%	39 weeks
Streetly et al. [3]	Relapsed	20	MTD Pom 5 mg every other day ± dexa	50%	10.5 months
Richardson et al. [4]	Relapsed/refractory	38	MTD Pom 4 mg 21/28 ± dexa	21%	4.6 months
Shah et al. [5]	Relapsed/refractory	32	MTD carfilzomib 20/27 mg/m^2 days 1, 2, 8, 9, 15, 16, pom 4 mg 21/28, dexa 40 mg weekly	50%	7.2 months
Richardson et al. [6]	Relapsed/refractory to lena	34	MTD pom 4 mg on days 1–14, bort 1.3 mg/m^2 on days 1, 4, 8, 11, and dexa 20 mg (10 mg for patients aged >75 years) on days 1, 2, 4, 5, 8, 9, 11, and 12	65%	Not reported
Shah et al. [7]	Relapsed/refractory	31	MTD oprozomib 210 mg on days 1, 2, 8, 9, 15, 16, 22, 23, pom 4 mg 21/28, dexa 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23	57%	Not reported
Chari et al. [8]	Relapsed/refractory	77	Daratumumab 16 mg/kg weekly for 2 cycles, then every 2 weeks for 4 cycles, and every 4 weeks until progression, pom 4 mg 21/28, dexa 40 mg weekly (20 mg for patients >75 years).	58.5%	Not reported
Phase I and II trials
Larocca et al. [9]	Relapsed/refractory to lena	24 (phase I) 55 (phase II)	MTD Pom 2.5 mg/day 28/28, cyclo at 50 mg every other day, prednisone at 50 mg every other day	51%	10.4 months
Lacy et al. [10]	Relapsed/refractory to lena	9 (phase I) 47 (phase II)	MTD Poma 4 mg 21/28 + bortezomib 1.3 mg/m^2 on days 1, 8, 15, 22 IV or SQ and + dexa 40 mg weekly	81% (44 evaluable patients)	17.7 months
Voorhees et al. [11]	Refractory to lena and PI	17	MTD Poma 4 mg 21/28 + ixazomib 4 mg on days 1,8,15 + dexa 40 mg weekly	62% (13 evaluable patients)	Not reported

Bort: bortezomib; Cyclo: cyclophosphamide; dexa: dexamethasone; IV: intavenously; lena: lenalidomide; MTD: maximum tolerated dose; ORR: overall response rate; PI: proteasome inhibitor; PFS: progression free survival; Pom: pomalidomide; SQ: subcutaneously.

Table 2. Pomalidomide phase II and III trials in multiple myeloma.

Authors	Disease status	No. of patients	Schedule	ORR	Median PFS
Phase II trials
Richardson et al. [12]	Relapsed/refractory	221 113	Pom 4 mg 21/28 + dexa 40 mg weekly versus Pom 4 mg 21/28	33% 18%	4.2 months 2.7 months
Lacy et al. [13]	Refractory to lena and bort	35 35	Pom 2 mg 28/28 + dexa 40 mg weekly versus Pom 4 mg 28/28+ dexa 40 mg weekly	25% 29%	6.5 months 3.2 months
Leleu et al. [14]	Refractory to lena and bort	43 41	Pom 4 mg 21/28 + dexa 40 mg weekly versus Pom 4 mg 28/28 + dexa 40 mg weekly	35% 34%	TTP: 5.8 months 4.7 months
Baz et al. [15]	Relapsed/refractory to lena	36 34	Pom 4 mg 21/28 + dexa 40 mg weekly versus Pom 4 mg 21/28 + dexa 40 mg weekly + Cyclo 400 mg on days 1, 8, 15	38.9% 64.7%	4.4 months 9.5 months
Badros et al. [16]	Relapsed/refractory	24	Pom 4 mg 21/28 + dexa 40 mg weekly + pembrolizumab 200 mg IV every 2 weeks	36.4%	Not reported
Phase III trials
San Miguel et al. [17]	Relapsed/refractory who have failed bort and lena	302 153	Pom 4 mg 21/28 + dexa 20 mg vs. dexa 40 mg on days 1–4, 9–12, 17–20	31% 10%	4 months 1.9 months
Dimopoulos et al. [18]	Relapsed/refractory who have failed bort and lena	682	Pomalidomide 4 mg 21/28 + dexa 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22	32.6%	4.6 months

Bort: bortezomib; Cyclo: cyclophosphamide; dexa: dexamethasone; lena: lenalidomide; ORR: overall response rate; PFS: progression free survival; Pom: pomalidomide; TTP: time to progression.

Schey SA, Fields P, Bartlett JB, 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.

 PubMed Web of Science ®Google Scholar

Streetly MJ, Gyertson K, Daniel Y, et al. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol. 2008;141:41–51.

 PubMed Web of Science ®Google Scholar

Richardson PG, Siegel D, Baz R, 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.

 PubMed Web of Science ®Google Scholar

Shah JJ, Stadtmauer EA, Abonour R, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015;126:2284–2290.

 PubMed Web of Science ®Google Scholar

Richardson PG, Hofmeister C, Raje NS, et al. A Phase 1, multicenter study of pomalidomide, bortezomib, and low-dose dexamethasone in patients with proteasome inhibitor exposed and lenalidomide-refractory myeloma (Trial MM-005). Blood. 2015;126:abstr 3036.

 Web of Science ®Google Scholar

Shah J, Niesvizky R, Stadtmauer E, et al. 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. 2015;126:abstr 378.

 Web of Science ®Google Scholar

Chari A, Lonial S, Suvannasankha A, et al. Open-label, multicenter, Phase 1b study of daratumumab in combination with pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma. Blood. 2015;126:abstr 508.

 Web of Science ®Google Scholar

Larocca A, Montefusco V, Bringhen S, et al. Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter Phase 1/2 open-label study. Blood. 2013;122:2799–2806.

 PubMed Web of Science ®Google Scholar

Lacy MQ, LaPlant BR, Laumann KM, et al. Pomalidomide, bortezomib and dexamethasone (PVD) for patients with relapsed lenalidomide refractory multiple myeloma (MM). Blood. 2014;124:abstr 304.

 Web of Science ®Google Scholar

Voorhees PM, Mulkey F, Hassoun H, et al. Alliance A061202. a Phase I/II Study of pomalidomide, dexamethasone and ixazomib versus pomalidomide and dexamethasone for patients with multiple myeloma refractory to lenalidomide and proteasome inhibitor based therapy: phase I results. Blood. 2015;126:abstr 375.

 Google Scholar

Richardson PG, Siegel DS, Vij R, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized Phase 2 study. Blood. 2014;123:1826–1832.

 PubMed Web of Science ®Google Scholar

Lacy MQ, Allred JB, Gertz MA, 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.

 PubMed Web of Science ®Google Scholar

Leleu X, Attal M, Arnulf B, et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: intergroupe Francophone du Myelome 2009-02. Blood. 2013;121:1968–1975.

 PubMed Web of Science ®Google Scholar

Baz RC, Martin TG, Lin H-Y, et al. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016;127:2561–2568.

 PubMed Web of Science ®Google Scholar

Badros AZ, Kocoglu MH, Ma N, et al. A Phase II study of a anti-PD-1 antibody pembrolizumab, pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2015;126:abstr 506.

 Web of Science ®Google Scholar

San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose 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;14:1055–1066.

 PubMed Web of Science ®Google Scholar

Dimopoulos MA, Palumbo A, Corradini P, et al. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood. 2016;128:497–503.

 PubMed Web of Science ®Google Scholar