EXTREME SERUM FREE LIGHT CHAINS RATIO IS AN EXTREME SERUM FREE LIGHT CHAINS RATIO IS AN INDEPENDENT PROGNOSTIC FACTOR FOR PROGRESSION IN INDEPENDENT PROGNOSTIC FACTOR FOR PROGRESSION IN

RELAPSE/REFRACTORY MULTIPLE MYELOMARELAPSE/REFRACTORY MULTIPLE MYELOMAM. OffidaniM. Offidani11, L. Corvatta, L. Corvatta22, S. Gentili, S. Gentili11, A. Savini, A. Savini11, C. Polloni, C. Polloni11, M. Brunori, M. Brunori22, M. Catarini, M. Catarini22, G. Visani, G. Visani22, F.Alesiani, F.Alesiani22, A. , A.

SamoriSamori22, M. Ferranti, M. Ferranti22, P. Fraticelli, P. Fraticelli22, B. Amoroso, B. Amoroso33, P. Leoni, P. Leoni11

11Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona; Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona; 22Marche Multiple Myeloma Marche Multiple Myeloma Network, GEMaMM, Italy and Network, GEMaMM, Italy and 33Scientific Director Freelite Italy, The Binding Site, Birmingham, UKScientific Director Freelite Italy, The Binding Site, Birmingham, UK

Although extreme free light chains ratio Although extreme free light chains ratio

(eFLCr: < 0.03 or > 32)(eFLCr: < 0.03 or > 32) and ISS have and ISS have

been found to be prognostic factors for been found to be prognostic factors for

survival in newly diagnosed multiple survival in newly diagnosed multiple

myeloma (MM), their usefulness in myeloma (MM), their usefulness in

relapsed/refractory myeloma have not relapsed/refractory myeloma have not

been explored so far.been explored so far.

RATIONALERATIONALE

ThaDD ThaDD (8%)(8%)

ThaDD-V ThaDD-V (36%)(36%)

EDA-V EDA-V (40%)(40%)

RD RD (16%)(16%)

We explored the impact of We explored the impact of age, ISS age, ISS stage, eFLCr, cytogenetics and stage, eFLCr, cytogenetics and duration of first remissionduration of first remission on on survival parameters in survival parameters in 87 patients87 patients with relapsed/refractory MM with relapsed/refractory MM treated within controlled trials with treated within controlled trials with regimens including:regimens including:

METHODSMETHODS

Age Age PS PS ≥ 2≥ 2ISS ISS 2-32-3Free light chain monoclonalityFree light chain monoclonality FLC ratio valueFLC ratio valueExtreme FLC ratioExtreme FLC ratioRenal failureRenal failureUnfavourable cytogeneticsUnfavourable cytogenetics2 microglobulin (mg/l)2 microglobulin (mg/l)

3.5 3.5 Albumin (g/dl)Albumin (g/dl)

3.5 g/dl3.5 g/dlDisease statusDisease status

relapserelapserefractoryrefractory

Prior chemotherapy lines > 2Prior chemotherapy lines > 2Prior PSCTPrior PSCTFirst remission duration < 12 monthsFirst remission duration < 12 months

No (%)No (%)

31 (36)31 (36)60 (69)60 (69)

56 (64)56 (64)31 (36)31 (36)

42 (48)42 (48)8 (9)8 (9)

24 (54)24 (54)

42 (52)42 (52)

36 (46)36 (46)

68 (78)68 (78)19 (22)19 (22)28 (32)28 (32)51 (59)51 (59)38 (44)38 (44)

Median (range)Median (range)

65 (31-82)65 (31-82)

8.3 (0-14200)8.3 (0-14200)

3.6 (0.2-21.5)3.6 (0.2-21.5)

3.6 (2.4-4.5)3.6 (2.4-4.5)

CHARACTERISTICS OF 87 PATIENTSCHARACTERISTICS OF 87 PATIENTS

CONCLUSIONSCONCLUSIONS

• As well as patients with newly diagnosed MM, those with advanced disease can be usefully stratified according to eFLCrAs well as patients with newly diagnosed MM, those with advanced disease can be usefully stratified according to eFLCr

• The FLCr should be included in the work-up of patients with relapsed/refractory disease The FLCr should be included in the work-up of patients with relapsed/refractory disease since it seemssince it seems helpful in tailoring treatment helpful in tailoring treatment

UNIVARIATE ANALYSIS FOR PFSUNIVARIATE ANALYSIS FOR PFS

Age > 65 (HR=1.5; p=0.433)Age > 65 (HR=1.5; p=0.433)

ISS stage 2-3 (HR=1.7; p= ISS stage 2-3 (HR=1.7; p= 0.0780.078))

eFLCr (HR=2.0; eFLCr (HR=2.0; p= 0.020p= 0.020))

Unfavorable FISH (HR=1.3; p= 0.345)Unfavorable FISH (HR=1.3; p= 0.345)

First remission < 12 months (HR=1.6; First remission < 12 months (HR=1.6; p=0.083p=0.083))

MULTIVARIATE ANALYSIS FOR PFSMULTIVARIATE ANALYSIS FOR PFS

eFLCr:eFLCr: HR= 1.9 (95%CI= 1.2-3.4); p= HR= 1.9 (95%CI= 1.2-3.4); p= 0.0300.030))

FLCr 0.03-32FLCr 0.03-32

No (%)No (%)

13 (29.5)13 (29.5)

20 (45.5%)20 (45.5%)

28 (62)28 (62)

FLCr 0.03-32FLCr 0.03-32

median = 22 monthsmedian = 22 months

p= 0.019p= 0.019

PFSPFS

FLCr< 0.03 or >32FLCr< 0.03 or >32

median = 10 monthsmedian = 10 months

p= 0.030p= 0.030

OSOS

FLCr 0.03-32FLCr 0.03-32

median = NRmedian = NR

FLCr< 0.03 or >32FLCr< 0.03 or >32

median = 17 monthsmedian = 17 months

ResponseResponse

CRCR

VGPRVGPR

PRPR

RESPONSE TO THERAPY RESPONSE TO THERAPY ACCORDING TO FLCrACCORDING TO FLCr

FLCr <0.03 or >32FLCr <0.03 or >32

No (%)No (%)

5 (12)5 (12)

20 (47.5)20 (47.5)

24 (57)24 (57)

FLCr 0.03-32FLCr 0.03-32

No (%)No (%)

13 (29.5)13 (29.5)

20 (45.5)20 (45.5)

28 (62)28 (62)

pp

0.0280.028

0.4680.468

0.5420.542