Heinz Ludwig©2018
Supportive Care in Multiple Myeloma
Prof. Heinz LudwigWilhelminen Cancer Research InstituteWilhelminenspital, Vienna, Austria
The 4th World Congress on Controversies in Multiple Myeloma (COMy)Paris, France May 3‐5, 2018
DisclosuresResearch Funding: Takeda, AmgenSpeaker‘s Bureau: Takeda, Amgen, Celgene, Bristol‐Myers Squibb, Janssen
Heinz Ludwig©2018
Why is supportive care essential?
• Markedly increased mortality rate due to infections within first months after start of initial therapy
• Infections remain the second most frequent cause of mortality during the course of the disease
• Acute myeloma‐associated renal failure is an emergency complication requiring fast work up and prompt treatment initiation
• Neuropathy, diarrhea, obstipation, thrombolic events, rash, and others impair QoL
• Toxicity of therapy frequently enforces treatment discontinuation or dose reduction
• Severe haematotoxicity (thrombopenia) precludes use of certain treatments
Heinz Ludwig©2018
Supportive care in multiple myeloma
Infections
Psychological distress
Diarrhea
Fatigue
Rash
Hematologic
Renal failure
Neuropathy
Pain
Constipation
Cardiac
Thrombosis
Bone disease
Tumor lysis
Bleeding
Hypercalcemia
Heinz Ludwig©2018
Risk factors for infections in multiple myeloma
1. Nucci M, Anaissie E. Clin Infect Dis 2009;49:1211–25;2. Blimark C, et al. Haematologica 2015;100:107–13.
InfectionMyeloma‐related
innate immunodeficiency
Older age
Myeloma therapies
Myeloma‐and treatment‐associated organ
dysfunction
Gender
B‐cell dysfunction (hypogammaglobulinaemia),
T‐cell, dendritic cell and NK‐cell abnormalities
Renal failure, pulmonary impairment, severe alimentary,
mucosal damage, hyper‐glycaemia, transfusional iron overload, myeloma‐associated
deposition diseases
Age‐related frailty, geriatric conditions, physical
dysfunctions, cognitive dysfunction, social isolation
20% higher risk in males
Neutropenia, mucositis,Catheter‐related infections
Heinz Ludwig©2018
Highly increased risk of infections
MGUS1: 2 x risk (pneumonia, osteomyelitis, sepsis, pyelonephritis cellulitis, endocarditis, meningitis, influenza, herpes
Myeloma2: bacterial ‐ 7 x risk, viral – 10 x riskunderlying cause of death: 22%
Grade 3 & 4 infectionsContinuous LenDex (FIRST Study3) 29%Carfilzomib LenDex (ASPIRE Study4) 16.5%
1 Kristinsson SY et al., Heamtologica 2012, 2 Blimack C et al., Hematologica 2014, 3 Benbouker l et al., NEJM 2014, 4 Jakubowiak ASH 2013
Heinz Ludwig©2018
Cumulative incidence of infection‐ and non infection‐related deaths
Blimark C et al., Haemtologica 2014
Infections accounted for 22% of deaths during the follow up period
Infection‐related Non infection‐relatedcauses of death
CV
Follow up of 9253 Swedish multiple myeloma patients
22% of mortalitywithin 2 months after DX
Heinz Ludwig©2018
Episodes of infections following diagnosis, and risk factors for infections
199 patients, Follow up (median): 33 months, 771 episodes of infections were identified.
Teh BW et al., Br J Heamatol 2015
Episodes with infection during 33 mos median FU
5.0%
63.3%
25.1%
6.5%
Hd Melphalan
Iv Cyclophosphamide
Combination chemotherapy
Cumulative dose of Glucocorticoids
Risk factors for infections
None 1‐4 5‐9 ≥10
Percen
tage
of patients
Cox regression analysis
Heinz Ludwig©2018
Treatment‐emergent infections during the first 18 monthsof therapy within the FIRST trial
Results pooled across treatment arms given the lack of difference in severe infections between the arms TE, treatment-emergent.
ECOG PS ≥ 2Hemoglobin ≤ 11 g/dLLDH ≥ 200 U/LSβ2M ≥ 6 mg/L
Risk factors for infection
Dumontet Ch et al. Leukemia in press
Time to grade ≥3 infections in pts w/o high‐risk factors for infection
Heinz Ludwig©2018
Sites of infection and involved microorganisms in 162 patients during ASCT
Park S et al, Transpl Infect Dis 2015: 17: 679‐687
Upper respiratory tract29.8%
26.0%
14.4%
4.8%
2.9%
Lower respiratory tract
Gastrointestinal
Urinary tract
Catheter‐related infection 1.9%Skin and soft tissue infection 2.9%Herpes simplex 2.9%Other 3.8%Unexplained fever 5.8%
Respiratory tract infectionInfluenza virus 10Influenza A (H1N1)/B 9 (3)/1Pneumococcus 9Mycoplasma 2Staphylococcus aureus 2Haemophilus influenzae 1Others 3GastroenteritisClostridium difficile toxin 3Catheter‐related infectionCoagulase‐neg. Staphylococcus 1
Urinary tract infectionEscherichia coli 2Skin and soft tissue infectionStreptococcus species 1
Herpes zoster
Heinz Ludwig©2018
Diagnostic measures – personal recommendations
Viral infections• PCR for adenovirus, RSV, CMV, HSV, VZV, EBV• Antigen detection in patient probes: RSV, Flu A&B, Adeno, VZV, HSV
• Antibody testing not informative• Cave: herpes sine herpete
Bacterial infections• Blood cultures• Septifast
Fungal infections (only during HD‐Dex, allo‐transplantation)• Candida – visual inspection – blood cultures• Aspergillus – CT thorax, galactomannan test, blood cultures
CT, computed tomography; HD-Dex, high-dose dexamethasone; HHV, Herpesviridae; PCR, polymerase chain reaction.
Heinz Ludwig©2018
90 samples, 56 from bonchoalveolar lavage and 34 from nasopharyngeal aspirates
All 90 samples
30 nasophyryngealsamples
Convential PCR testing FilmArray respiratory panel*
Hammond SP et al., J Clin Med 2012
*multiplex PCRtests for 21 respiratorypathogens
** PIV=parainfluenza
**
Methodology for detection of infectious agents is still in it‘s infancy
Other techniques presently assessed: Mass spectrometry, NGS
Heinz Ludwig©2018
Recommendations for vaccination of patients with MM
Ludwig H et al., Leukemia 2018 in press
Vaccine Recommendation No. of doses
Timing after ASCT Comment
Influenza Tri‐ or quadri‐valent vaccine1
annually 4‐6 mo. Should be repeated in case of insufficient response
PneumococciNDMM: PCV13 3 6‐12 mo. Newly diagnosed, pneumococcal vaccine‐nai ̈ve patients
Followed by: PPSV 23 1 ≥12 mo.>8 weeks after completion of PCV13
Response rate to PCV 23: 57%
Herpes zoster Vaccination after ASCT 1May be considered at ≥24 mo. (if no GVHD or ongoing
immunosuppression)
A varicella‐zoster virus glycoprotein E subunit vaccine candidate was shown to be highly effective in controls
Haemophilus influenzaetype b Vaccination 3 6‐12 mo.
Hepatitis A
Vaccination of pts and nonimmune close contacts living/travelling to endemic
areas
2 6‐12 mo. All patients should be tested for hepatitis A, in case of negative results vaccination is recommended
Hepatitis B
Vaccination of pts and nonimmune close contacts living/travelling to endemic
areas
3 6‐12 mo. Patients should be tested for hepatitis B, in case of negative results vaccination is recommended
Meningococcal conjugate Recommended in high‐risk patients 1‐2 6‐12 mo. High‐risk: patients with splenectomy or complement deficiency
Live vaccines Generally not recommendedMay be considered at ≥24 mo. (if no GVHD or ongoing
immunosuppression)
Measles, mumps, and rubella (MMR), varicella zoster, Bacillus Calmette‐Guerin, oral typhoid and yellow fever, life influenza virus
(intranasal live) and oral polio (live)
Ludwig H et al, Leukemia 2018
Heinz Ludwig©2018
A second influenza vaccine dose may boost immune response in MM patients
13 1019
0
35
19
40
15
54
38
63
31
0
20
40
60
80
100
Infl. A(H3N2)
Infl. B Infl. A(H1N1)
All strains
Cumulative % of p
atients
Seroprotection
Pre‐vaccine 1st vaccine 2nd vaccine
48 patients with multiple myeloma
Hahn M, et al. Haematologica 2015;100:e285.
34
6
27
6
50
23
52
17
0
20
40
60
80
100
Infl. A(H3N2)
Infl. B Infl. A(H1N1)
All strainsCu
mulative % of p
atients
Seroconversion
1st vaccine 2nd vaccine
Heinz Ludwig©2018
Levofloxacin 500mg/d*R
Placebo for 3 months
Febrile episodes or death < first 3 months
Infection or death 27% vs 19%, p=0.002
*40% of patients had prophylactic trimethoprim, in addition• Levoflaxacin reduced gram‐negative infections
• Sulfamethoxazol‐Trimetoprim reduced gram‐postive infections
• No difference in carriage of or infections with C. difficile, MRSA and ESBLGnB between both arms
Prophylactic Antibiotics vs Control during first 3 Months after Treatment Initiation
Drayson MT et al., Blood 2017, 130: 930
977 patients
Heinz Ludwig©2018
When to use antibiotic prophylaxis?
• Elderly Patients
• Patients with frequent episodes of infections
• Particularly if risk for febrile neutropenia is high
• Limit prophylaxis to episodes of poorly controlled myeloma
• Flurochinolone, TMP‐SMX , Amoxicillin
• Consider Metronidazole if relapsing Clostridia infections
• In case of suspected bacterial infection and active disease:
• Act promptly, start antibiotic treatment and diagnostic tests
Heinz Ludwig©2018
Consider IV immunoglobulin prophylaxis in selected patients only
Time to first infection
Patients with poor antibody response to Pneumovax showed the greatest benefit
Only patients in plateau phase were enrolled
1IVIG Prophylaxis vs Placebo in MM patientsduring ‚plateau phase‘
1Chapel HM, et al. Lancet 1994;343:1059–63,.
IVIg, intravenous immunoglobulin
Heinz Ludwig©2018
Metaanalysis on IV immunoglobulin prophylaxis in patients with MM and CLL
Metaanalysis of major IVIG infection trials 1, 2,3 comparing IVIg with Placebo or no treatment
1Chapel HM, et al. Lancet 1994;343:1059–63, 2 Cooperative Goup NEJM 1988 3 Boughton BL et al., Clin Lab Haematol 19754. Terpos E, et al. Haematologica 2015;100:1254–66 5Ludwig H et al., Leukemia 2018
Prophylactic immunoglobulin replacement is not routinely recommended;4,5 however, it may be useful in a subset of patients with severe, recurrent bacterial infections and
hypogammaglobulinaemia4
Heinz Ludwig©2018
Prophylaxis and treatment recommendations for viral infections
Viral infections Prophylaxis Treatment
Herpes simplexAciclovir, valaciclovir or famciclovir Pts on PI & on
DaratumumabElotuzumab
7–14 days of aciclovir, valaciclovir or famciclovir
Herpes zosterAciclovir, valaciclovir or famciclovir
7–14 days of aciclovir, valaciclovir or famciclovir
Cytomegalovirus None14–21 days of ganciclovir or valganciclovir or foscarnet, cidofovir, leflunomide, maribavir, letermovir
Influenza Vaccination Oseltamivir for 5–7 days, peramivir*
Respiratory syncytial virus
NoneRibavirin 200 mg 3x/day, for 2 weeks
Epstein–Barr virus NoneNone establishedRituximab – B‐cell depletion, CMV‐antivirals!
Adenovirus None Cidofovir
Ludwig H et al., Leukemia 2018, in press*per infusion only
Heinz Ludwig©2018
Prevalence of renal failure
• 20‐ 30% of patients have renal impairment at presentation1,2
• 50% at some time during the course of their disease
• < 3% present with acute renal failure
• 2‐ 5% of myeloma patients require long‐term dialysis
• Increased risk of infections and early death3
1Alexanian et al. Arch Intern Med 1990;150:1693–1695, 2Kyle et al. Mayo Clin Proc 2003;78:21–33 3Blade et al. Arch Intern Med 1998;158:1889–1893
Heinz Ludwig©2018
Acute Renal Failure
Prerenal Intrinsic Postrenal
Tubulointerstitial Glomerular
Reduced perfusionVascular disease
Obstructive uropathy
Acute tubular necrosisAcute interstitial nephritis
Cast nephropathy
GlomerulonephritisVasculitis
Amyloidosis*
*usually not ‚acute‘
Heinz Ludwig©2018
Tamm‐Horsefall protein binds topatient‐specific CDR3 region of light chains
695 amino acids211‐220 amino acids
Light chain Tamm‐Horsefall protein
9 Amino acidbinding region
Heinz Ludwig©2018
Pathophysiology of cast nephropathy
Hutchison CA et al., Nat Rev Nephrol. ; 8(1): 43–51. 2011
Heinz Ludwig©2018
Diagnostic workup
Dimopoulos MA et al., JCO 2016
S‐creatinine and eGFR (CKD‐EPI or MDRD formula), Urea, Na, K, Ca, Total protein, electrophoresis, and immunofixation of a sample of 24‐h urine collection, S‐FLCs
Proteinuria consisting mainly of LCFLCs high (i.e >500‐1,500mg/L)
Nonselective proteinuria or significant albuminuria or FLCs low (i.e <500mg/L)
Renal biopsy not necessary, but helpful for excluding/diagnosis of other renal pathology
Consider amyloidosis or MIDD or other comorbidconditions: Renal biopsy is often necessary
Heinz Ludwig©2018
Monoclonal gammopathy of renal significance (MGRS)
Leung N, et al. submitted.
Lesion % with MIgdeposits
% with detectable MIg
% with MM
% with MGRS
% with Other HC
Light chain cast nephropathy 100 100 99 0 ~1AIg amyloidosis 96 99 16 80 1‐4MIDD 100 100 0‐20 78‐100 1‐2Light chain proximal tubulopathy 100 97 12‐33 61‐80 3‐8Cryoglobulinemic (I & II) glomerulonephritis 100 90‐100(I)
/49(II)6‐8(I) 0(II) 47‐52 (I)
20(II)24‐56(I) 7(II)
PGNMID 100 30‐32 4 96 ~1Crystal‐storing histiocytosis 83 90 33 8 50Cryocrystalglobulin/crystalglobulin
nephropathy
91 82 61 18 4
Immunotactoid glomerulonephritis 69‐93 63‐71 0‐13 25‐50 25‐50
C3 glomerulopathy with MGRS 0 28‐83 0‐40 40‐90 6‐10Monoclonal fibrillary glomerulonephritis 15‐17 7‐17 0‐54 55‐98 2‐10
Heinz Ludwig©2018
Management of PP induced renal failure (RF)
Exclude (or confirm contribution of) non‐paraprotein‐induced causes of RF (NSAID, hypercalcemia, contrast media, antibiotics, sepsis)
• Treat complicating diseases (infections)
• Hydration, control fluid balance, blood pressure
• Avoid nephrotoxic drugs
• Bisphosphonates or denosumab
• Alkalinisation of urine
• Start anti‐myeloma therapy ASAP
• Role of extended dialysis with high‐output dialysismembrane is controversial as yet
Heinz Ludwig©2018
PNP investigator assessment
0%10%20%30%40%50%60%70%80%
BL n=80
C1 n=79
C2 n=71
C3 n=65
C4 n=59
C5 n=46
C6 n=40
C7 n=31
C8 n=27
EOT n=26
Grade 1,2Grade 3,4
0%
20%
40%
60%
80%
BL/C1n=78
C2n=76
C3n=66
C4n=58
C5n=51
C6n=38
C7n=31
C8n=24
EOTn=24
PNP patient self assessment
Grade 1, 2
Grade 3, 4
Ludwig H et al., ASH 2013 abstract
Polyneuropathy: Physicians underestimate the severity of PNP
Patients treated with 9 cycles of Bortezomib‐Bendamustine‐Dexamethasone
Heinz Ludwig©2018
Dose adjustment rules for thalidomide‐ andbortezomib‐induced peripheral neuropathy
Severity of neuropathy Thalidomide dose adjustment Bortezomib dose adjustmenta
Grade 1 (asymptomatic;
paresthesia, weakness and/or loss of
reflexes) with no pain or loss of
function
Continue to monitor the patient with clinical examination. Consider
reducing dose if symptoms worsen. However, dose reduction is not
necessarily followed by improvement of symptoms.
None;
consider SC and/or weekly administration
Grade 1 with pain or grade 2
(moderately symptomatic; interfering
with function but not with activities of
daily living)
Reduce dose or interrupt treatment and continue to monitor the
patient with clinical and neurological examination. If no improvement
or continued worsening of the neuropathy, discontinue treatment. If
the neuropathy resolves to Grade 1 or better, the treatment may be
restarted, if the benefit/risk is favorable.
Reduce dose to 1.0 mg/m2 twice weekly or
change treatment schedule to 1.3 mg/m2
once per week; use SC administration
Grade 2 with pain or grade 3
(severely symptomatic; interfering
with activities of daily living)
Discontinue treatment Withhold treatment until symptoms of
toxicity have resolved. When toxicity
resolves re‐initiate treatment, and reduce
dose to 0.7 mg/m2 once per week.
Grade 4 (neuropathy which is disabling)
and/or severe autonomic neuropathy
Discontinue treatment Discontinue treatment
Modified according to Ludwig H et al, Leukemia 2018
Heinz Ludwig©2018
Opioids antagonistsMorphin, Hydromorphon,Dihydrocodein, Tramadol, Tapentadol*
antagonistsOxycodon, Nalbuphin
Muscle relaxantsTolperisonBaclofen
Ca‐antagonistsNifedipine
Anticonvulsive agentsGabapentin (Neurontin®)Pregabalin (Lyrica®)Carbamazepin (Tegretol®)
AntidepressantsTricyclic (Amitriptylin, Nortryptilin)SSRIs (Paroxetin, Maprotilin, Bupriopion,
Dulexitin)
Topic therapiesEMLALidocain 5% (Versatis®)Capsaicin 0.075% (Qutenza®)
Treatment of neuropathic pain
*µ Agonist and Noradrenalin reuptake inhibitor
Heinz Ludwig©2018
Patient‐related risk factors (RF)
Infection
Surgery
Previous VTE
Progressive disease
Cardiovascular disease
Immobilization
Old age, obesity
Blood clotting disorders
Hyperviscosity
Treatment‐related risk factors (RF)
Hd Dexamethasone
Erythropoietin
Doxorubicin
Thalidomide
Lenalidomide
Pomalidomide
Hormone therapy in ♀ Polychemotherapy
0 or 1 Pt‐related RF ≥2 Pt‐related RF
Aspirin (81‐325 mg/d) LMWH or full dose cumarin LMWH or full dose cumarin
VTE prophylaxis during TX with IMiDs: Risk factor‐based recommendations
Modified according to Kristinsson SY. ASH Edcuation Program Book, 2010: 437‐444; Palumbo et al. Leukemia 2008;22:414–423
Heinz Ludwig©2018
Edoxaban – a novel direct oral anticoagulant shows similar efficacy and bleeding risk in cancer patients
Raskob GE et al., NEJM 2017
1046 cancer patients with previous VTE.
LMWH for at least 5 days followed by oral edoxaban (60 mg daily)R
Dalteparin, 200 IU/kg, daily for 1 month, followed by dalteparin 150 IU/kg daily TX for 6 - 12 months
Incidence of thromboembolic complications Incidence of major bleeding
11.3%
7.9% 6.9%
4.0%
Heinz Ludwig©2018
Management of VTEs
• Novel anticoagulants have recently been shown to be effective in patients with cancer1
• Optimal duration of prophylaxis not defined, most experts discontinue LMWH or WAR prophylaxis in patients with well controlled disease
• In case of VTE: discontinue myeloma TX, escalate or continue anti‐thrombotic TX, resume IMIDs when full anticoagulation is established
• Relapse rate of VTE significantly reduced with long term prophylaxis
• Episodes of VTE do not impair OS
• Major adverse event of thromboprophylaxis: bleeding• Prophylactic doses of LMWH or aspirin confer little risk of major bleeding• Novel anticoagulants and warfarin confer a slightly higher risk of bleeding
1Young et al, Abstract 625, ASH 2017
Heinz Ludwig©2018
Rash: Lenalidomide associated
Skin rash usually is mildRarely • Erythema multiforme• Acute febrile neutrophilic dermatosis • Stevens‐Johnson syndrome • Toxic epidermal necrolysis
*Package insert
Skin and subcutaneoussystem disorders* Len-TX Placebo
Rashc 75 (21.1) 33 (9.4)
Sweating Increased 35 (9.9) 25 (7.1)
Dry Skin 33 (9.3) 14 (4.0)
Pruritus 27 (7.6) 18 (5.1)
Heinz Ludwig©2018
Treatment recommendations for lenalidomide‐induced rash
Grade 1: wait & see or topical steroids and/or antihistamines
Grade 2: topical steroids and/or antihistamines
Grade 3: discontinue therapy, oral steroids
Grade 4: discontinue therapy, oral/iv steroids.
Week Monday Thirsday Wednesday Tuesday Friday Saturday Sunday
1 2.52 2.5 2.53 2.5 2.54 5.0 5.05 7.56 7.5 7.5
In case of severe AEs and lenalidomide being the last treatment option try to desensitize the patient to lenalidomide
van de Donk NWCJ, et al. Cancer Manag Res. 2012;4:253‐68, 2Lee MJ et al., Br. J Heamatol 2014.
Heinz Ludwig©2018
Causes of diarrhea in multiple myeloma
• Bortezomib, IMiDs, high‐dose chemotherapy
• Bacteria (Clostridium difficile, Shigella, Salmonella)
• Viruses (CMV, Adeno‐, Entero‐, Noro‐virus)
• Protozoa (Lamblia, Entamoeba histolytica)
• Graft vs host disease in patients undergoing allogeneic transplantation
• Bile salt malabsorption (primary bile acid diarrhea)*
*75Se into the SeHCAT molecule (taurine conjugated bile acid analogue, retention measured on day 7 after ingestion
Heinz Ludwig©2018
Causes of diarrhea in multiple myeloma
• Bortezomib, IMiDs, high‐dose chemotherapy
• Bacteria (Clostridium difficile, Shigella, Salmonella)
• Viruses (CMV, Adeno‐, Entero‐, Noro‐virus)
• Protozoa (Lamblia, Entamoeba histolytica)
• Graft vs host disease in patients undergoing allogeneic transplantation
• Bile salt malabsorption (primary bile acid diarrhea)*
*75Se into the SeHCAT molecule (taurine conjugated bile acid analogue, retention measured on day 7 after ingestion
Heinz Ludwig©2018
Treatment of diarrhea in multiple myeloma
• Opioids (Loperamide)
• Opiods plus atropin (Lomotil®)
• Antisecretory agents
• Somatostatin
• Long acting somatostatin
• Bismuth subsalicylate
• Rehydration
• Electrolyte supplementation
• Bile acid binder Colesevelam (Cholestagel®)
Heinz Ludwig©2018
Colesevelam improves lenalidomide‐associated diarrhea in MM
10 pts with severe Lenalidomide‐induced diarrheaColesevelam*, a bile acid binder (up to 6 tablets a day and not within 4 hours of LEN administration)
Improvement of symptoms, often within a few days
Pawlyn C, et al. EHA 2014:abstract P1006. Poster presentation.* Cholestagel in EU, Welchol in US
Heinz Ludwig©2018
Somnolence, thirst, nausea, increasing pain
Heinz Ludwig©2018
Treatment of hypercalcaemia
1 can only be administered in patients with GFR ≥ 30ml/min, 2 Dose adaptation in renal failure required
Rehydration, normal saline
3–6 L/day, 500 mL/h Monitor fluid balance
Furosemide 80–100 mg/day Start furosemide after replacement of fluid deficit; monitor and replace electrolytes (especially potassium and magnesium)
Calcitonin 5–10 U/kg in 500 mL saline over 6hrs, followed by the same dose, s.c., once or twice daily
Causes a rapid drop of calcium,but tachyphylaxis sets in soon.
Corticosteroids 40 mg dexamethasone, d1‐d4 Reduces Ca resorption, anti‐myeloma effect
Bisphosphonates
Zoledronate1 4 mg as 15‐minute infusion
Start after replacement of fluid deficitafter 24–48 hours
Pamidronate1 60–90 mg
in 1 L saline over 4 h
Ibandronate2 4‐8 mgas slow intravenous injection
Dialysis in selected patients, avoid nephrotoxic drugs
Heinz Ludwig©2018
Denosumab for hypercalcemia in patientsresistant or previously treated with bisphosphonates
Denosumab 120mg, d 1, 8, 15, 29; thereafter 4 weekly
HU MI et al. JNCI 2013
Heinz Ludwig©2018
Conclusions
• Prevention and treatment of adverse events is of key importance in the management of
patients with multiple myeloma
• Reduces the need for treatment discontinuation
• Enhances the efficacy of treatment
• Reduces the need for hospitalization
• Maintains/improves quality of life
• Reduces mortality
• Is an essential element in the management of patients with MM
Heinz Ludwig©2018
Thank you for your attention