Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Relapsed Myeloma: Long Term Follow up and Factors Predicting Outcome in 345 Patients MQ. Lacy, S. Kumar, B. LaPlant, K. Laumann, M.Gertz, S. Hayman, F. Buadi, A. Dispenzieri, J. Lust, S. Russell, D. Dingli, S. Zeldenrust, R. Fonseca, P. L. Bergsagel, V. Roy, T. Sher, A. Chanan Khan, A. K. Stewart, C. Reeder, S.V. Rajkumar, J.R. Mikhael

Mayo Clinic

Scottsdale, Arizona

Rochester, Minnesota

Mayo Clinic College of Medicine Mayo Clinic Comprehensive Cancer Center

Jacksonville, Florida

Phase 1 trials Patient population

N

Regimen/dose

ORR

Schey

Relapsed

24

Pom dose escalation MTD 2mg 28/28

54%

Streetly

Relapsed

20

Pom +/- dex MTD 5 mg QOD 28/28

50%

Richardson

Rel/refr

38

Pom +/- dex MTD 4 mg 21/28

25%

Richardson

Len/Btz ref

120

Pom +/- dex, 4 mg, 21/28

25%

Lacy

Rel, 1-3 reg

60

Pom/dex 2 mg, 28/28

63%

Lacy

Len ref

34

Pom/dex 2 mg, 28/28

47%

Leleu

Len/Btz ref

43 40

Pom/dex 4 mg, 21/28 Pom/dex 4 mg, 28/28

30% 47%

Lacy

Len/Btz ref

35 35

Pom/dex 2 mg, 28/28 Pom/dex 4 mg, 28/28

49% 43%

Mark

RR/MM

52

Cla/ Pom +/- dex, 4 mg, 21/28

60%

Phase 2 trials

Mayo Myeloma Pom/Dex Trials, 345 patients Cohort

Group

Dose

N

Accrual dates

2, 28/28

60

Nov 2007 - Aug 2008

mg/day 1

Relapsed < 4 prior reg

2

Len refractory

2, 28/28

34

Nov 2008 - April 2009

3

Bortez/Len refractory

2, 28/28

35

May 2009 - Nov 2009

4

Bortez/Len refractory

4, 28/28

35

Nov 2009 - April 2010

5

Len refractory

4, 28/28

61

May 2010 – Nov 2010

4, 21/28

120

April 2011 – March 2012

3%

Follow-up Total (N=344) Progression Status No Progression Progression

102 (30%) 242 (70%)

Follow-up Status Alive Dead

213 (62%) 131 (38%)

Number of Cycles Median Range

5 (0-60)

Currently Receiving Treatment

37

Reason for Ending Treatment Adverse Event Disease Progression Died on Study

7% 75% 4%

Hematologic toxicity

Non hematologic toxicity, seen in at least 5%

Other Non Hematologic toxicities • Pneumonitis • All grades: 2% • Grade 3+: 1% • VTE 3% • Second malignancy 3 (1%)

Responses 2mg Relapsed ≤ 3 Reg All cycle Confirmed Response Rate No. of Responders Median time to response

2mg 4mg 2mg Len Bortz/Len Bortz/Len Refractory Refractory Refractory

4mg Relapsed ≤ 3 Reg

4mg Relapsed D 1-21

65%

32%

26%

29%

38%

23%

39

11

9

10

23

28

1.7 mo

2.0 mo

1mo

1.4mo

1.1mo

1.1mo

Change in the measurable parameter from baseline (serum, urine, FLC)

Responses Overall, N=344 IMWG criteria Response

Number

%

CR/sCR

17

5%

VGPR

42

12%

PR

61

18%

MR

45

13%

SD

127

37%

PD

43

13%

NR

9

1%

CBR > MR 48% ORR > PR 35% > VGPR 17%

Patient Outcomes 2mg Len Refractory

2mg Bortz/Len Refractory

4mg Bortz/Len Refractory

4mg Relapsed ≤ 3 Reg

4mg Relapsed D 1-21

21 mo

8 mo

15 mo

3 mo

22 mo

10 mo

Median Overall Survival1

NA

33mo

16mo

14 mo

NA

14mo

9 Month OS

91%

81%

68%

54%

83%

66%

13 mo

5 mo

6 mo

3 mo

8 mo

4 mo

Median Duration of response1

Median Progression Free Survival1

2mg Relapsed ≤ 3 Reg

Mo: month; NA: Not attained 1) Kaplan Meier Estimate, median (95% confidence interval)

Response and DOR in High Risk Groups 17p-

t(4;14)

t(14;16)

Del 13 (Cytogenetics)

56

24

11

50

147

12 (21%)

3 (13%)

5 (45%)

12 (24%)

44 (30%)

sCR/CR

1

0

0

0

3

VGPR

5

1

2

2

16

PR

6

2

3

10

25

Duration of Response

8 mo

5 mo

10 mo

7 mo

8 mo

# Events

9

3

5

10

37

N Response Rate

mSMART high Risk

Predictors of response Parameter

Fish 17p- (Yes) t(4;14) (Yes) mSMART risk (High) B2M (>5.5) Number of Prior Regimens (>3) LDH > ULN Previous lenalidomide(Yes) Previous bortezomib (Yes) HGB ( ULN (Yes vs No) Prior Bortezomib (Yes vs No) Number of Prior Regimens (>3 vs ≤3)

p-value