M. OffidaniM. Offidani11, A. Savini, A. Savini11, L. Corvatta, L. Corvatta22, C. Polloni, C. Polloni11, S. Gentili, S. Gentili11, A. Brioni, A. Brioni33, G. Visani, G. Visani22, P. Galieni, P. Galieni22, F. Alesiani, F. Alesiani22, M. Brunori, M. Catarini, M. Brunori, M. Catarini22, A. Mele, A. Mele22, M. Burattini, M. Burattini22, A. Samori, A. Samori22, R. Centurioni, R. Centurioni22, N. Blasi, N. Blasi22, M. Ferranti, M. Ferranti22, P. Fraticelli, P. Fraticelli22, R. Rizzi, R. Rizzi22, P. Leoni, P. Leoni11

11 Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti Ancona, Ancona, Italy; Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti Ancona, Ancona, Italy; 22 Marche Multiple Myeloma Network, GEMaMM, Italy; Marche Multiple Myeloma Network, GEMaMM, Italy; 33 Istituto di Ematologia e Oncologia Medica Seragnoli, Bologna, Italy Istituto di Ematologia e Oncologia Medica Seragnoli, Bologna, Italy

Studies including thalidomide showed a rate of severe Studies including thalidomide showed a rate of severe infectious complications, ranging from 6% to 22%, that infectious complications, ranging from 6% to 22%, that maybe represent life-threatening adverse event or maybe represent life-threatening adverse event or compromise compliance to therapy. Therefore antibacterial compromise compliance to therapy. Therefore antibacterial prophylaxis has become a routine clinical practice despite prophylaxis has become a routine clinical practice despite its role in the new-drugs era has to be defined.its role in the new-drugs era has to be defined.

We performed a post-hoc analysis of We performed a post-hoc analysis of 224 patients224 patients treated treated with with thalidomide based combinationsthalidomide based combinations in order to: in order to:

1.1. assess time, type and outcome of infectionsassess time, type and outcome of infections

2.2. search for factors affecting onset of infections during search for factors affecting onset of infections during induction and build a risk model in order to perform induction and build a risk model in order to perform targeted prophylaxis.targeted prophylaxis.

CharacteristicsCharacteristics

AgeAge> 65 yrs> 65 yrsDisease statusDisease status

newly diagnosednewly diagnosedrelapsed/refractoryrelapsed/refractory

PS (ECOG)PS (ECOG) 01-23-4

ISSISSII-III

Prior lines of therapyPrior lines of therapy11> 2> 2

Renal failureRenal failureUnfavourable cytogeneticUnfavourable cytogeneticAntiinfective prophylaxisAntiinfective prophylaxis

No (%)No (%)

141 (63)

119 (53)105 (47)

77 (34)129 (58)

18 (8)

156 (69)

49 (22)55 (25)38 (17)45 (32)

168 (75)

Median (range)Median (range)

70 (31-91)

Characteristics HR 95%CI p

Monoclonal Component > 2 g/dl 2,4 1,5 - 5,7 0,015

Plateles count < 130.000/µl 2,1 1,3 - 4,2 0,026

Prophylaxis: NO 2,1 0,7 - 5,2 0,198

Newly diagnosed 1,9 0,8 - 4,3 0,210

CONCLUSIONSCONCLUSIONS

ParametersParametersAgeAge

6565> 65> 65

SexSexMMFF

Performance statusPerformance status0-10-12-42-4

ImmunophenotypeImmunophenotypeIgAIgAOtherOther

Previous DVTPrevious DVTYesYesNoNo

Bone marrow plasmacellsBone marrow plasmacells 30%30%> 30%> 30%

Monoclonal componentMonoclonal component 2 gr/dL2 gr/dL> 2 gr/dL> 2 gr/dL

Hb levelHb level< 11 gr/dL< 11 gr/dL 11 gr/dL11 gr/dL

PLT countPLT count< 130000/< 130000/ll 130000/130000/ll

2-microglobulin 2-microglobulin 3.5 mg/dL3.5 mg/dL> 3.5 mg/dL> 3.5 mg/dL

Albumin Albumin 3.5 g/dL3.5 g/dL> 3.5 g/dL> 3.5 g/dL

ISSISS112-32-3

CRP CRP normalnormalabnormalabnormal

CreatinineCreatinine 2 mg/dL2 mg/dL> 2 mg/dL> 2 mg/dL

Disease statusDisease statusnewly diagnosednewly diagnosedrelapsed/refractoryrelapsed/refractory

Prior ASCTPrior ASCTyesyesnono

ProphylaxisProphylaxisYesYesNoNo

%%

17171818

20201414

17172020

17171717

32321616

16162020

10102121

16161919

22221212

17171818

16161818

23231616

17171616

18181616

13132222

16161818

15152525

OROR

0.9200.920

1.5831.583

0.8030.803

0.9720.972

0.3920.392

0.7560.756

0.4080.408

0.8230.823

0.4810.481

0.9800.980

1.1431.143

1.6051.605

1.1341.134

1.1501.150

0.5540.554

0.8750.875

0.5240.524

pp

0.8200.820

0.2000.200

0.5600.560

0.9500.950

0.0520.052

0.5190.519

0.5200.520

0.5930.593

0.0470.047

0.9560.956

0.7170.717

0.1960.196

0.7460.746

0.7720.772

0.0960.096

0.7700.770

0.0840.084

UNIVARIATE ANALYSIS OF UNIVARIATE ANALYSIS OF FACTORS AFFECTING INFECTIONSFACTORS AFFECTING INFECTIONS

86 patients 86 patients (38,5%)(38,5%) developed an infection developed an infection 39 patients 39 patients (17,5%)(17,5%) developed grade 3-4 infection developed grade 3-4 infection

23 pneumonia (1 CMV, 1 probable fungal infection)23 pneumonia (1 CMV, 1 probable fungal infection)9 FUO9 FUO6 bacteremia (all due to Gram- bacteria)6 bacteremia (all due to Gram- bacteria)1 orbital abscess1 orbital abscess

INDUCTION THERAPY:INDUCTION THERAPY:•42 patients 42 patients ThaDD-VThaDD-V•160 patients 160 patients ThaDDThaDD

•5 patients 5 patients VDTVDT•8 patients 8 patients TDTD

•9 patients 9 patients VMPTVMPT

INTERMEDIATE RISK GROUPINTERMEDIATE RISK GROUP

p= 0,921

Prob

abili

ty o

f in

fect

ion

months

Patients without prophylaxisPatients with prophylaxis

HIGH RISK GROUPHIGH RISK GROUP

p= 0,004

Prob

abili

ty o

f in

fect

ion

months

Patients without prophylaxis

Patients with prophylaxis

18%18% 2%2%

monthsPr

obab

ility

of s

ever

e in

fect

ion

p=0,023

months

High risk group (3 risk factors)Intermediate risk group (2 risk factors)Low risk group (1 risk factor)

Prob

abili

ty o

f sev

ere

infe

ctio

n

months

Prog

ress

ion

free

surv

ival

Patients without infection

Patients with infection

months

•Despite antibiotic prophylaxis, patients receiving thalidomide combination therapy develop infections particularly pneumoniapneumonia•Higher risk patients are those with bulk diseasebulk disease, represented by high MC and low platelets count• Infections don’t compromise both compliance to therapy and outcome but they worse patients QoL and significantly increase costs of care•Severe infections increase the risk of DVTDVT•High risk patients should receive more suitable antimicrobial prophylaxis

Cum

ulat

ive

risk

Probability of infectioninfection

Probability of DVTDVT

months

Infectious complications in patients with Multiple Myeloma treated withInfectious complications in patients with Multiple Myeloma treated withnew-drug combinations including Thalidomidenew-drug combinations including Thalidomide