Table 4. Survival Outcomes and Best Response Rates for MM-002 and MM-003

Variable MM-002 MM-003

POM + LoDEX (n = 112)

POM (n = 108)

POM + LoDEX (n = 302)

HiDEX (n = 153)

Median PFS, mos (95% CI) 4.2a (3.6–5.5) 2.7 (1.9–2.9) 4.0b (3.6-4.7) 1.9 (1.9–2.2)

Median OS, mos (95% CI)16.5c

(12.4–18.5)13.6

(9.6–18.1)13.1d

(11.0–15.4)8.1

(6.9–9.2)ORR (≥ PR), n (%) 37 (33) 19 (18) 97 (32) 17 (11)Median Tx duratione, mos (range) 5.0 (0.1–34.8) 4.7 (0.1–35.7) 4.2 (0.1–21.4) 1.8 (0.2–15.9)

a P = 0.003 POM + LoDEX vs. POM. b P < 0.001 POM + LoDEX vs. HiDEX. c P = 0.709 POM + LoDEX vs. POM.d P < 0.001 POM + LoDEX vs. HiDEX.e Safety population.CI, confidence interval; HiDEX, high-dose dexamethasone; LoDEX, low-dose dexamethasone; mos, months; ORR, overall response rate; POM, pomalidomide; PR, partial response; Tx, treatment.

Presented at the 55th Annual Meeting of the American Society of Hematology (ASH); New Orleans, LA, USA; December 7–10 2013.

BACKGROUND• Relapsed and refractory multiple myeloma (RRMM) patients (pts) following

treatment (Tx) with bortezomib (BORT) or IMiDs® immunomodulatory agents, have limited Tx options, and outcomes remain poor1

• The immunomodulatory agent pomalidomide (POM) has demonstrated potent antimyeloma activity

• Tx with POM is recommended in pts who have received at least 2 prior Tx, including lenalidomide (LEN) and BORT, and have demonstrated disease progression on or within 60 days of completion of their last Tx2

• Randomized phase 2 and 3 trials (MM-002 and MM-003) have shown prominent efficacy results with combination POM plus low-dose dexamethasone (POM + LoDEX) Tx in RRMM pts who had received multiple prior Tx, including LEN and BORT3–5

OBJECTIVE• To present a side-by-side analysis of the current efficacy and safety outcomes

based on the MM-002 and MM-003 trials

METHODSStudy Design• The study designs for MM-002 and for MM-003 are shown in Figure 1 and

Figure 2, respectively

• Primary endpoint: Progression-free survival (PFS)

• Secondary endpoints: Response rate, duration of response (DOR), OS, and safety

Key Inclusion Criteria• Inclusion criteria were similar for the MM-002 and MM-003 trials

• Age ≥ 18 years

• In the POM + LoDEX groups, AEs were managed through dose reductions (29% and 27%) or interruptions (67% and 67%), supportive care with granulocyte-colony stimulating factor (46% and 43%), blood transfusions (45% and 49%), platelet transfusions (14% and 20%), and anti-infective agents (89% in both trials), in the MM-002 and MM-003 trials, respectively

• The rate of discontinuations due to AEs in the POM + LoDEX groups was low (2–4%)

– Rate of POM discontinuation due to infection was low (1% in MM-002 and 2% in MM-003)

– One pt discontinued Tx due to neutropenia in both trials – No pts discontinued Tx due to febrile neutropenia

• Although 60% and 50% of pts receiving POM + LoDEX in the MM-002 and MM-003 trials, respectively, had a history of PN at baseline, only 18% and 17% of PN was observed in the study

– Four (1%) pts developed Gr ≥ 3 or greater neuropathy in the MM-003 trial

– PN that occurred in study improved or resolved in half of the pts in the MM-002 trial (55%)

conclusions• This side-by-side analysis of the MM-002 and MM-003 trials consistently

showed that the combination regimen of POM + LoDEX extends PFS in RRMM pts

– Median PFS was 4.2 and 4.0 months, respectively – PFS, OS, and ORR were not negatively impacted in pts who were refractory to LEN or BORT, even as last prior Tx

– Occurrence of neutropenia did not seem to affect the incidence of infections

• POM was generally well tolerated with dose modifications and supportive care, leading to few discontinuations due to AEs

• POM + LoDEX could be a Tx option for pts with advanced RRMM who have exhausted LEN and BORT Tx

references1. Kumar SK, et al. Leukemia. 2012;26:149-57.2. Pomalyst® (pomalidomide). Prescribing information,

February 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204026lbl.pdf

3. Richardson PG, et al. Blood. 2011;118:abstract 634.4. Vij R, et al. J Clin Oncol. 2012;30 Suppl:abstract 8016.5. San Miguel, et al. Lancet Oncol. 2013;14:1055-66.

AcknowledgmentsThe authors would like to thank the patients who volunteered to participate in these studies, the staff members at the study sites who cared for them, and the representatives of the sponsors who were involved in data gathering and analyses. The authors acknowledge the financial support for this study from Celgene Corporation. The authors received editorial assistance and printing support from Excerpta Medica (Kathy Boon, PhD) sponsored by Celgene Corporation.

disclosuresD.S.S.: Celgene, Millennium, Onyx, Merck – advisory board, honoraria and speakers bureau P.G.R.: Celgene, Millennium, Johnson & Johnson – advisory boardM.A.D.: Celgene, Ortho-Biotech – consultant/advisor; Genesis Pharma – research funding C.C.: Roche – honoraria; Johnson & Johnson – consultancy, research funding; Lundbeck – consultancy; Celgene – consultancy, research funding; GlaxoSmithKline – research fundingK.S.: Celgene, Janssen – consultancy, honoraria, and research fundingR.V.: Celgene – consultancy, research funding, and speakers bureau; Millennium – speakers bureau; Onyx – consultancy and research fundingN.B.: Johnson & Johnson – honoraria and research funding; Celgene – honorariaR.B.: Celgene, Millennium, Bristol-Myers Squibb, Novartis – research fundingC.C.H.: Celgene – advisory board and honorariaK.C.W.: Celgene – consultant/advisor, honoraria

S.J.: Celgene, Millennium, MSD, Onyx – honoraria and membership of an entity’s board of directors or advisory committeesS.L.: Millennium, Celgene, Novartis, Bristol-Myers Squibb, Onyx, Merck – consultancyM.D.: Celgene, Janssen – consultant/advisor, research fundingP.M.: Celgene, Millennium, Janssen – consultant/advisor, honorariaJ.S.M.: Novartis, Roche, Pfizer, GSK, Astellas – consultant/advisor, honorariaL.K.: Celgene – consultant/advisor, honoraria, expert testimony, other remuneration; Janssen – honoraria, other remunerationH.G.: Celgene – consultant/advisor, honoraria, research fundingA.B., M.L.: Celgene – research fundingA.O.: Celgene – consultant/advisorA.A.: Celgene, Janssen - Membership on an entity’s Board of Directors or advisory committees, research fundingP.C., L.S., M.H.Z., C.J.: Celgene – employment and equity ownership

M.C.: Celgene, Janssen, Millennium, Onyx and Bristol-Myers Squibb – consultancy, honoraria, Membership on an entity’s Board of Directors or advisory committeesK.C.A.: Celgene, Millennium, Bristol-Myers Squibb, Onyx – membership on board of directors or advisory committee; Acetylon, Oncopep – scientific founder

POM (4 mg D1–21of each 28-day cycle)

Option to addLoDEX

(40 mg/week)a Discontinueand follow up

for survivaland

subsequenttreatment

Progressivedisease

Progressivedisease

ProgressivediseasePOM (4 mg D1–21

of each 28-day cycle) + LoDEX (40 mg/week)a

Ran

dom

izat

ion

Figure 1. Study Design of MM-002 Open-Label, Phase 2 Study

(n = 302)POM 4 mg/day D1–21 +

LoDEX 40 mg (≤ 75 years)20 mg (> 75 years)

D1, 8, 15, 22

Follow-up for OSand SPM until 5

years post-enrollment

Companion trialMM-003C

POM 21/28 days

PDa or intolerable AE

Thromboprophylaxis with low-dose aspirin, low-molecular-weight heparin, or equivalent was required for all ptsreceiving POM and those at high risk for thromboembolic events

PDa(n = 153)

HiDEX 40 mg (≤ 75 years)20 mg (> 75 years)D1–4, 9–12, 17–20R

and

omiz

atio

n 2:

1 (N

= 4

55)

Figure 2. Study Design of MM-003 Open-Label, Phase 3 study

Efficacy and Safety of Pomalidomide Plus Low-Dose Dexamethasone in Advanced Multiple Myeloma: Results of Randomized Phase 2 and 3 Trials (MM-002/MM-003)

P3185

• Pts with RRMM:

– Measurable levels of M-protein in serum or urine – ≥ 2 prior Tx (≥ 2 cycles of LEN and ≥ 2 cycles of BORT, separately or in combination)

– Refractory disease with documented progression during or within 60 days of last Tx

– Pts refractory to both LEN and BORT were allowed to enter the study

David S. Siegel1, Paul G. Richardson2, Meletios A. Dimopoulos3, Christine Chen4, Kevin Song5, Ravi Vij6, Nizar Bahlis7, Rachid Baz8, Craig C. Hofmeister9, Katja C. Weisel10, Sundar Jagannath11, Sagar Lonial12, Michel Delforge13, Moshe Talpaz14, Philippe Moreau15, Jesús San Miguel16, Lionel Karlin17, Hartmut Goldschmidt18, Anne Banos19, Albert Oriol20, Adrian Alegre21, Laurent Garderet22, Michele Cavo23, Valentina Ivanova24, Joaquin Martinez-Lopez25, Martha Lacy26, Min Chen27, Philomena Casey27, Lars Sternas27, Mohamed H. Zaki27, Christian Jacques27, Kenneth C. Anderson2

1John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; 2Dana-Farber Cancer Institute, Boston, MA, USA; 3Alexandra Hospital, Athens, Greece; 4Princess Margaret Hospital, Toronto, Canada; 5Vancouver General Hospital, Vancouver, Canada; 6Washington University School of Medicine, St Louis, MO, USA; 7Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada; 8H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 9Ohio State University, Columbus, OH, USA; 10University Hospital Tuebingen, Tuebingen, Germany; 11Mount Sinai Medical Center, New York, NY, USA; 12Emory University School of Medicine, Atlanta, GA, USA; 13University Hospital Leuven, Leuven, Belgium; 14University of Michigan Comprehensive Cancer Center, MI, USA;

15University Hospital Hôtel-Dieu, Nantes, France; 16Hospital Universitario de Salamanca, IBSAL, IBMCC/CSIC, USAL, Salamanca, Spain; 17Centre Hospitalier Lyon Sud/Hospices Civils de Lyon, Pierre-Bénite, France; 18University Hospital, Heidelberg, Heidelberg, Germany; 19Centre Hospitalier de la Côte Basque, Bayonne, France; 20Institut Catala d’Oncologia, HGTiP, Barcelona, Spain; 21Hospital Universitario La Princesa, Madrid, Spain; 22Université Pierre et Marie Curie, Paris VI, Hôpital Saint Antoine, Paris, France; 23Institute of Hematology “Seràgnoli”, S. Orsola’s University Hospital, Bologna, Italy; 24GUZ Moscow City Clinical Hospital S.P. Botkin, Moscow, Russia; 25Hospital Universitario 12 de Octubre, Madrid, Spain; 26Mayo Clinic, Rochester, MN, USA; 27Celgene Corporation, Summit, NJ, USA

Aspirin (81–100 mg) or equivalent was mandated for all patients. a Pts aged > 75 years had a starting DEX dose of 20 mg/week.D, days; LoDEX, low-dose dexamethasone; POM, pomalidomide; pts, patients.

a Progression of disease was independently adjudicated in realtime.AE, adverse event; D, days; HiDEX, high-dose dexamethasone; LoDEX, low-dose dexamethasone; PD, progressive disease; POM, pomalidomide; pts, patients; SPM, second primary malignancy.

Table 1. Key Exclusion Criteria

MM-002 MM-003POM + LoDEX (n = 112) POM + LoDEX (n = 302)

Prior history of malignancies, other than MM

Unless pt had been free of disease for ≥ 3 years

Unless pt had been free of disease for ≥ 5 years

Prior Tx –POM Tx, hypersensitivity to thalidomide, LEN, or DEX; or resistance to high-dose DEX

Peripheral neuropathy grade ≥ 2 ≥ 2Absolute neutrophil count (cells/mL) < 1,000 < 1,000Platelet count (cells/mL)

< 50% plasma cells> 50% plasma cells

< 75,000< 30,000

< 75,000< 30,000

Serum creatinine (mg/dL) > 3.0 –Creatinine clearance (mL/min) – < 45Serum liver transaminase level > 3.0 x upper limit of normal > 3.0 x upper limit of normalSerum calcium (mmol/L) – > 3.5Serum bilirubin level > 2.0 mg/dL > 34.2 µmol/L

DEX, dexamethasone; LEN, lenalidomide; LoDEX, low-dose DEX; MM, multiple myeloma; POM, pomalidomide; pt, patient; Tx, treatment.

Assessments• Data cut-off was February 1 2013 for MM-002 and September 1 2013 for

MM-003; median follow-up was 14.2 and 10.0 months, respectively

• Response rate and efficacy data were evaluated by investigator assessment based on best response assessment using EBMT criteria

• Adverse event (AE) severity was graded according to NCI-CTC v3.0

Dose Modification Schedule• Treatment-emergent AEs (TEAEs) were managed using dose reductions,

Tx interruptions, and supportive care

• The dose modification schedule for POM (per protocol) is shown in Table 2

Table 2. Dose Modification Schedule Per Protocol

Toxicity POM dose modificationa

Gr ≥ 2 hypo-hyperthyroidismHold dose, initiate appropriate Tx, maintain DL at next cycle at discretion of treating physician

Gr 3 rash Hold dose, decrease by 1 DL at next cycle (resolve to Gr ≤ 1)

Gr 3 peripheral neuropathy Hold dose, decrease by 1 DL at next cycle (resolve to Gr ≤ 1)

Gr ≥ 3 constipationHold dose, initiate bowel regimen, decrease by 1 DL at next cycle, at discretion of treating physician

Gr ≥ 3 venous thromboembolismHold dose, initiate anticoagulation, maintain DL at next cycle, at discretion of treating physician

Gr 4 neutropenia or febrile neutropeniaHold dose, initiate G-CSF, reduce by 1 DL at next cycle if neutropenia was not the only DLTTo initiate next cycle of POM: platelet count ≥ 500/μL

Gr 4 thrombocytopeniaHold dose, decrease by 1 DL at next cycleTo initiate next cycle of POM: platelet count ≥ 50,000/μL

Gr 4 rash or rash with blistering Discontinue study drug and discontinue pt from study

Gr 4 peripheral neuropathy Discontinue study drug and discontinue pt from study

Other Gr ≥ 3 POM-related adverse events Hold dose, decrease by 1 DL at next cycle (resolve to Gr ≤ 2)a POM DL: 4 mg to 3 mg to 2 mg to 1 mg then discontinuation.DL, dose level; DLT, dose-limiting toxicity; G-CSF, granulocyte colony-stimulating factor; Gr, Grade; POM, pomalidomide; pt, patient; Tx, treatment.

results

Baseline Characteristics• In MM-002, the intent-to-treat efficacy analysis included 112 pts in the

POM + LoDEX group and 108 pts in the POM alone group

– 60% of pts in the POM alone group received LoDEX upon progression – 79% were LEN refractory – 62% were refractory to both LEN and BORT – 39% received LEN as last prior Tx

• In MM-003, 302 pts were treated with POM + LoDEX and 153 pts with high-dose dexamethasone (HiDEX)

– 50% of pts in the HiDEX group subsequently received POM – 95% were LEN refractory – 75% were refractory to both LEN and BORT – 24% had received LEN as last prior Tx

• Baseline characteristics and prior Tx are summarized in Table 3 for pts in both studies receiving POM + LoDEX

– The majority of pts (93%) had advanced disease (Durie Salmon stage ≥ II) – The median number of prior Txs was 5 (range 2–14) – Most pts were refractory to LEN (90%)

Table 3. Baseline Characteristics

MM-002 MM-003POM + LoDEX (n = 112) POM + LoDEX (n = 302)

Male, n (%) 62 (55) 181 (60)Age, median (range), years 64 (34–88) 64 (35–84)ECOG performance status score, n (%)

0–1 100 (88) 248 (82)2–3 13 (12) 52 (17)

Cytogenetic profile, n (%)High riska 30 (27) 130 (43)Standard riskb 57 (50) 91 (30)

Median number of prior Tx (range) 5 (2–13) 5 (2–14)Type of prior Tx,c n (%)

LEN/BORT/steroids 113 (100) 300 (100)LEN as last therapy 44 (39) 71 (24)BORT as last therapy 56 (50) 108 (36)

Alkylators 105 (93) 300 (100)SCT 82 (74) 214 (71)Thalidomide 77 (67) 173 (57)Anthracycline 55 (49) 172 (57)

a High-risk cytogenetic profile is defined as those with abnormalities in 13q14, 17p13, 4p16/14q32, or 14q32/16q23.b Standard risk is defined as any cytogenetic abnormality in 17p13 or 4p16/14q32.c Pts could receive > 1 therapy.BORT, bortezomib; LEN, lenalidomide; LoDEX, low-dose dexamethasone; POM, pomalidomide; pts, patients; SCT, stem cell transplantation; Tx, treatment.

Tolerability and Safety• The most common Gr 3/4 TEAEs for pts receiving POM + LoDEX were

neutropenia, anemia, thrombocytopenia, and pneumonia (Table 5)

– The percentages of pts with neutropenia (all grades) was similar in both trials (49% in MM-002 vs. 51% in MM-003)

– In the MM-003 trial there were 26% pts with Gr 3 neutropenia and 22% with Gr 4 neutropenia

– A higher percentage of pts with pneumonia (all grades) was seen in the MM-002 trial (33%) vs. MM-003 trial (15%)

– Incidence of deep-vein thrombosis was low (all grades: 2.7% in MM-002 and 3.0% in MM-003)

– The majority of infections occurred in the absence of neutropenia of any grade (54% in MM-002 and 66% in MM-003)

Table 5. Summary of AEs in the Safety Populations of the POM+ LoDEX arms in MM-002 and MM-003

MM-002 MM-003POM + LoDEX

(n = 112)POM + LoDEX

(n = 300)Most common hematologic Gr 3/4 AEs, n (%)

Neutropenia 46 (41) 147 (49)Anemia 25 (22) 99 (33)Thrombocytopenia 21 (19) 67 (22)

Most common nonhematologic Gr 3/4 AEs, n (%)Pneumonia 25 (22) 42 (14)Bone pain 14 (13) 21 (7)Fatigue 16 (14) 16 (5)

Hematologic Gr 3/4 TEAEs occurring in ≥ 10% of pts, n (%)Febrile neutropenia 3 (3) 29 (10)Leukopenia 11 (10) 26 (9)

Nonhematologic Gr 3/4 TEAEs occurring in ≥ 10% of pts, n (%)Dyspnea 14 (13) 15 (5)Back pain 11 (10) 15 (5)

AE of interest (all grades), n (%)DVT/PE 3 (3) 9 (3)Peripheral neuropathy 12 (11) 51 (17)Discontinuation of POM due to any AEs, n (%) 8 (7) 26 (9)

PN With POM Tx, n (%)Pts with PNa 20 (18) 45 (15)Pts with improvement/resolution, n (%) 11 (55) 3 (1)Median time to resolution, mos 4.6 (95% CI: 0.5–17.7) 0.1 (range: 0.1–1.1)

a PN includes 6 selected preferred terms: hyperesthesia, neuropathy peripheral, peripheral sensory neuropathy, paresthesia, hypoesthesia, and polyneuropathy.

AE, adverse event; CI, confidence interval; DVT, deep-vein thrombosis; LoDEX, low-dose dexamethasone; mos, monthsPE, pulmonary embolism; POM, pomalidomide; PN, peripheral neuropathy ; pts, patients; TEAE, treatment-emergent AE.

Response• The survival outcomes and best response rates for the MM-002 and MM-003

trials are shown in Table 4

• Survival outcomes were similar between the 2 trials

– MM-002: At a median follow-up of 14.2 months the median PFS was 4.2 months; OS was 16.5 months; and overall response rate (ORR, defined as at least a partial response) was 33% with POM + LoDEX

– MM-003: At a median follow-up of 15.4 months the median PFS was 4.0 months; OS was 13.1 months; and ORR was 32% with POM + LoDEX

– In both trials, LEN as last prior Tx did not impact response, PFS, or OS vs. the overall population Scan this QR code to receive the PDF file of the poster