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