3115 Evolving Treatment Trends in Relapsed/Refractory Multiple Myeloma in Europe from 2016 to 2018: Analysis of a Multi-National Survey Maximilian Merz,1 Isabelle Vande Broek,2 Manuel Pérez,3 Brigitte Kolb,4 Argiris Symeonidis,5 Emmanouil Nikolousis,6 Athanasios Zomas,7 Francisco Gonzalez,7 Lenka Kellermann,8 Hartmut Goldschmidt1 1University of Heidelberg, Heidelberg, Germany; 2AZ Nikolaas, Sint Niklaas, Belgium; 3Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; 4CHU de Reims, Hopital Robert Debré, Reims, France; 5University of Patras Medical School, Patras, Greece; 6University Hospital Birmingham, Birmingham, United Kingdom; 7Takeda Pharmaceuticals International AG, Zurich, Switzerland; 8Oncology Information Service, Freiburg, Germany

Drivers of treatment selection Figure 7. Proportions of patients receiving daratumumab-based treatment as 2nd-, 3rd-, and ≥4th-line therapy, by year and region • The frequencies of key disease, patient, and treatment journey characteristics among all patients and among patients receiving select key 40 regimens for 2nd-line and ≥3rd-line therapy in 2018 are summarized in Table 4 and Table 5, respectively. Background Objective 35 35 • Among patients receiving IMiD-based therapies in subsequent lines, the rates of prior IMiD treatment were significantly lower than in the overall 35 31 population.

% − Conversely, the rates of prior PI exposure were lower than average among patients receiving Kd and DVd at 2nd line, and higher than 30 27 27

1–11 s, 26 • Recently, treatment options for RRMM have increased substantially with multiple approvals of novel agents and combinations (Table 1). • To investigate the management of RRMM across Europe and understand the impact of recently approved novel regimens on real-world t 25 average among patients receiving Rd-based therapies at 2nd line.

n 24 24

12 e – Patients with RRMM now generally receive a range of different doublet or triplet regimens. i 25 • At 2nd line, the proportions of patients with ISS Stage III disease were higher among those receiving KRd, Kd, DRd, and DVd but lower among treatment patterns. t a 20 • These approvals have made the MM treatment algorithm increasingly complex, with changes driven chiefly by access to novel agents p those receiving Dd, IRd, and R/Rd.

f 20 o 17 and regimens. − Conversely, the proportion of patients having a prior biochemical relapse was higher among patients subsequently receiving IRd.

n 15 15 o • Furthermore, patient and disease characteristics have a profound impact on treatment decision-making. i • The groups receiving KRd and DRd included higher proportions of younger and fitter patients. t 15 13 r

o 11 − However, there was a lower-than-average rate of cardiac comorbidities in those patients receiving KRd. p 10 9 9 o Table 1. Key treatment options approved for RRMM since 2015 r 10 7 • Of note, at 3rd line the treatment choices are also driven by access to novel-agent-based regimens in the prior 2nd-line setting. P 5 5 3 Agent Regimen Study Median US US label EU EU label Methods 5 1 1 1 age, yrs* approval approval 0 0 Table 4. Patient/disease and treatment journey characteristics (%) among patients in 2018 receiving specific 2nd-line regimens 0 Carfilzomib KRd ASPIRE1 64 July 2015 1–3 prior lines Nov 2015 ≥1 prior therapy 2016 2017 2018 2016 2017 2018 2016 2017 2018 Characteristic Any regimen* KRd Kd DRd DVd Dd IRd R/Rd • This multi-national survey (iREAL) extracted retrospective, anonymized data from patients with RRMM treated in academic or community All patients DACH Non-DACH 2 Kd ENDEAVOR 65 Jan 2016 1–3 prior lines July 2016 ≥1 prior therapy hospitals and practices in eight selected European countries from January 2016 to December 2018. 2nd-line 3rd-line ≥4th-line Age <70 years 38.7 46.8 41.3 49.2 37.5 46.2 39.9 32.1 ECOG PS ≤1 64.6 77.5 32.6 70.9 66.7 71.8 63.8 61.8 Ixazomib IRd TOURMALINE-MM13 66 Nov 2015 ≥1 prior therapy Nov 2016 ≥1 prior therapy − Center selection was conducted based on epidemiologic research and analysis; the patient sample was determined by considering the distribution of the treated prevalence on the healthcare providers, the regional population density, and the healthcare structure. • Proportions of patients receiving specific key novel treatment regimens are summarized in Table 2. Cardiac comorbidities 36.2 20.0 60.4 25.4 33.3 38.5 35.6 38.3 − Data were analyzed overall and for Germany, Austria, and Switzerland (DACH) versus other countries (Belgium, France, Greece, ISS Stage III 42.1 52.8 60.4 54.0 61.1 25.6 27.0 32.2 Daratumumab Single-agent SIRIUS4 63.5 Nov 2015 ≥3 prior lines May 2016 RRMM (prior therapy (inc. a PI and an IMiD) inc. a PI and an IMiD) Spain, and UK; non-DACH) due to differences in treatment access. Table 2. Change in rates of use of key novel treatment regimens in Europe, 2016 to 2018 High-risk cytogenetics† 10.8 13.1 5.9 5.3 6.9 7.7 14.1 8.4 • Patients with RRMM, defined as undergoing ≥2nd-line treatment, who were receiving treatment on a regular or other type of prescription or Prior SCT 22.7 28.9 10.8 30.2 20.8 30.8 25.8 17.8 DRd POLLUX5 65 Nov 2016 ≥1 prior therapy April 2017 ≥1 prior therapy Regimen, %* 2nd-line therapy 3rd-line therapy 4th-line therapy on a named-patient program, were included. Prior PI treatment 77.0 95.8 56.9 87.3 34.7 89.7 89.0 82.5 6 − Centers reported all RRMM patients treated in the reporting period retrospectively back to initial diagnosis based on data in the patients’ 2016 2017 2018 2016 2017 2018 2016 2017 2018 DVd CASTOR 64 Nov 2016 ≥1 prior therapy April 2017 ≥1 prior therapy Prior IMiD treatment 16.8 3.2 37.8 11.1 62.5 7.7 9.2 8.2 files; treatment course data were updated and new RRMM patients were included quarterly. D-Pom-dex EQUULEUS7 64 June 2017 ≥2 prior therapies N/A N/A Carfilzomib-based triplets (KRd) 7.9 11.4 12.7 6.3 4.9 3.7 6.2 4.3 4.7 Initiated in university hospital 40.4 18.5 13.9 14.3 18.1 28.2 41.7 49.6 − Patients receiving treatment in clinical trials were excluded. (inc. a PI and R) Biochemical relapse 30.2 25.2 35.1 23.8 34.7 35.9 44.2 28.5 − Data on prior 1st-line treatment were gathered retrospectively from patient records. Carfilzomib-based doublets (Kd) 4.3 7.7 9.0 5.4 10.5 9.6 9.9 9.8 8.4 Elotuzumab Elo-Rd ELOQUENT-28 67 Nov 2015 1–3 prior therapies May 2016 ≥1 prior therapy Biochemical and symptomatic • Treatment regimens were classified according to the ‘leading agent’ in the combination: Ixazomib-based (IRd) 0.5 3.0 5.1 1.5 3.9 8.9 0.9 8.2 8.2 54.1 62.0 47.6 55.0 43.1 30.8 48.5 56.7 relapse 9 − PI-based regimens included bortezomib-based, carfilzomib-based, and ixazomib-based regimens, and could include doublets and Elo-Pom-dex ELOQUENT-3 69 Nov 2018 ≥2 prior therapies Aug 2019 ≥2 prior therapies DRd 0.2 2.2 5.9 0 2.7 6.0 0.2 2.3 3.6 (inc. a PI and R) (inc. a PI and R) triplets in combination with IMiDs (but not mAbs) Symptomatic relapse 14.6 10.6 16.3 21.2 20.8 30.8 6.1 13.9 − IMiD-based regimens included thalidomide-based, lenalidomide-based, and pomalidomide-based regimens that did not also include a DVd 0 0.5 2.3 0 1.6 6.8 0.6 2.3 4.7 Colored cells denote significant positive (green) or negative (red) difference from values for ‘any regimen’ (p<0.05, multivariate analysis). Pomalidomide Pom-Vd OPTIMISMM10 67 N/A N/A May 2019 ≥1 prior regimen (inc. R) PI or a mAb *Not all regimens included in ‘any regimen’ are represented in the table. Dd 0.1 0.6 1.2 4.7 8.0 10.1 19.3 20.5 21.6 †Presence of del17, t(4;14), or t(14;16). (Approval Pom-dex MM-00311 64 Feb 2013 ≥2 prior therapies Aug 2013 ≥2 prior regimens − mAb-based regimens included daratumumab-based and elotuzumab-based regimens, and could include single-agent use, doublets, prior to 2015) (inc. a PI and R) (inc. V and R) and triplets in combination with PIs or IMiDs. Elo-based 0.6 2.0 1.9 1.6 2.4 3.4 1.1 3.2 3.3 *Median age shown for investigational arm. Pom-based 1.0 1.0 0.7 25.5 21.3 20.7 22.2 15.6 16.5 Table 5. Patient/disease and treatment journey characteristics (%) among patients in 2018 receiving specific ≥3rd-line regimens

*% of treated patients with regimen data. Characteristic Any regimen* KRd Kd DRd DVd Dd IRd R/Rd

• Rates of treatment initiation due to biochemical relapse (based on M-protein level only, no symptoms) are summarized in Figure 4. • The progression-free period (time from start of one line to start of next line) decreased with increasing number of relapses (Table 3). Age <70 years 38.6 57.9 43.5 41.7 39.7 37.3 40.0 33.6 • Approximately one third of patients manifested an asymptomatic rather than clinical relapse. − Further investigation is needed to clarify these trends over time. ECOG PS ≤1 58.3 72.9 46.4 62.1 65.4 51.7 57.8 76.0 − The reason for the apparent decrease in rate of biochemical relapses from 2016 to 2018 in later lines of therapy is not clear. Cardiac comorbidities 34.0 27.1 41.0 31.8 35.9 33.3 31.1 32.6 Results Table 3. Median time from start of one line of therapy to start of subsequent line, by year ISS stage III 39.6 28.0 52.3 53.8 57.7 39.1 46.2 25.7 Figure 4. Proportion of patients with biochemical relapse by line High-risk cytogenetics† 9.9 12.1 15.1 3.0 8.3 12.6 12.4 7.2 Treatment period 2016 2017 2018 2016 2017 2018 Prior SCT 34.4 58.9 30.5 27.3 23.7 36.5 40.0 37.2 Patient disposition and characteristics 40 36 35 Start of 1st-line (including SCT) N 802 1034 1144 Prior PI treatment 93.7 94.4 83.3 99.2 95.5 96.3 97.3 92.4 34 to start of 2nd-line treatment • The total number of patients included was 2,782 in 2016, 3,902 in 2017, and 4,658 in 2018, including: 35 33 32 % 31 Prior IMiD treatment 72.6 60.7 79.1 42.4 62.8 80.6 75.1 59.2 − 1,202, 1,704, and 2,047 in DACH countries (Germany: 1,024, 1,469, 1,805; Austria: 101, 124, 139; Switzerland: 77, 111, 103) 30 Median progression-free period, months (range) 35 (0–198) 35 (0–198) 34 (0–210)

s, 28 t 30 − 1,580, 2,198, and 2,611 in non-DACH countries (Belgium: 101, 202, 268; France: 617, 820, 974; Greece: 91, 95, 76; Spain: 411, 586, 640; n Initiated in university hospital 39.7 42.1 39.7 25.8 21.2 41.5 45.3 52.6 e

i Start of 1st-line (no SCT) N 1814 2649 3298 t 23 UK: 360, 495, 653). a 25 to start of 2nd-line treatment Biochemical relapse 26.3 29.9 20.5 15.9 23.7 20.5 35.6 32.9 p

f Median progression-free period, months (range) 17 (0.5–380) 14 (0.5–380) 15 (0.7–380) • Of the patients enrolled who initiated a new treatment in 2016, 2017, and 2018, 40%, 49%, and 51%, respectively, were in 3rd line or beyond o 20 Biochemical and symptomatic

n 52.3 56.1 56.5 47.0 46.2 60.1 47.6 43.1

o relapse

(Figure 1). i

t 15

r Start of 2nd-line to start of N 1250 1210 668

− This potentially reflects the increasing availability of treatment options for RRMM and extended survival in MM. o

p 3rd-line treatment Symptomatic relapse 19.4 12.1 20.9 30.3 28.8 17.1 14.7 23.4

o 10 r Median progression-free period, months (range) 16 (0.4–96) 14 (0.5–96) 13 (0.5–96) P Figure 1. Line of therapy in which RRMM patients initiated a new treatment, by year 5 Colored cells denote significant positive (green) or negative (red) difference from values for ‘any regimen’ (p<0.05, multivariate analysis). Start of 3rd-line to start of N 507 574 331 *Not all regimens included in ‘any regimen’ are represented in the table. 2nd line 3rd line ≥4th line 0 4th-line treatment †Presence of del17, t(4;14), or t(14;16). 100% 2nd line 3rd line ≥4th line % Median progression-free period, months (range) 11 (0.5–71) 9 (0.6–71) 9 (0.9–67) 18% s, 24% 21% t

n 80% 43% e

i 49%

t 52% 25% Treatment patterns a

p 25% 31%

Treatment sequencing f 60% • The proportion of patients treated with triplet regimens increased in all lines of therapy from 2016 to 2018, reflecting the adoption of newly o

n approved triplets in RRMM, particularly in DACH countries (Figure 5). • From 2016 to 2018, prior IMiD exposure among patients receiving 2nd-line therapy increased from 28% to 32% overall, including from 11% to o i 40% t r − The limited adoption in non-DACH countries in later lines may be associated with delayed access and possibly limited availability of 20% in DACH (Figure 8). o 57% p 51% 48% − This may be associated with the approval of Rd as frontline therapy in Europe in February 2015 and the approval of lenalidomide as o additional triplet options following relapse/refractoriness to prior regimens.

r 20%

P post-ASCT maintenance therapy in Europe in February 2017. Conclusions 0% Figure 5. Proportions of patients receiving monotherapy, doublets, and triplets as 2nd-, 3rd-, and ≥4th-line therapy, − Among patients receiving 3rd-line therapy, there was an increase in prior IMiD exposure from 77% to 82% in all countries, reflecting the 2016 2017 2018 by year and region uptake of novel triplet combinations. n=2,316 n=2,896 n=2,956 − Rates of prior IMiD exposure appeared higher in non-DACH versus DACH, associated with a higher rate of frontline thalidomide use in 2nd-line regimens 3rd-line regimens ≥4th-line regimens • Multiple drug approvals for RRMM in Europe have resulted in marked changes in the treatment algorithm, with a certain non-DACH countries. 100% 100% 100% more immediate impact in countries with earlier access to new treatment options. • The data revealed a real-world population that was older and with poorer PS than RCT populations, and that had a substantial 2 2 2 2 3 3 1 2 1 4 9 • Most patients were IMiD-exposed or IMiD-refractory at ≥4th line (data not shown). 8 9 10 11 10 10 9 11 15 comorbidity burden. 90% 90% 19 19 19 17 90% 26 21 24 • Multiple decision drivers – such as age, fitness, comorbidities, and prior treatment – are associated with the use • Median age at diagnosis for patients enrolling in 2016, 2017, and 2018, was 68, 69, and 70 years, respectively. 80% of different novel regimens as 2nd-line and 3rd-line therapy. − 23%, 24%, and 26% of these patients were aged >75 years. 80% 80% Figure 8. Prior and current treatment with IMiDs as induction or maintenance in 1st- and/or 2nd-line therapy among patients − 58%, 57%, and 58% of patients were male. 70% 54 51 56 70% 70% currently receiving 2nd- or 3rd-line therapy in (A) 2016 and (B) 2018 − Results from RCTs are taken into consideration when making treatment choices and regimens are 62 58 41 • Median age at 2nd-, 3rd- and ≥4th-line was 71–73 years. 71 66 48 42 57 60% 72 72 60% 61 57 67 53 60% 42 implemented in real-world practice across patients of all ages and levels of performance status. 1–3, 5–7, 8, 10, 11 65 63 64 47 44 50 1st-line 1st-line − These real-world patients appear older than phase 3 RRMM RCT populations, in which median age was 64–67 years. 51 41 (A) (B) 50% 47 1st- + 2nd-line • Approximately one third of patients had an ECOG PS ≥2 at 2nd line in 2016–2018, increasing to >40% at ≥4th line (Figure 2). 50% 50% 1st- + 2nd-line 94.5% • The increasing range of treatment options has resulted in patients receiving more lines of therapy for RRMM, 1–3 90.6% − This compares to reported rates of ECOG PS 2 of 5–10% in phase 3 RRMM RCTs. 2nd-line 2nd-line 87.6% highlighting the need for cautious planning of treatment sequencing to optimize the use of available combinations 40% 40% 40% 84.8% 87.3% 81.4% 82.2% 78.6% according to patient characteristics and disease factors. 30% 30% 30% 76.8% 77.0% 75.4% Figure 2. Proportion of patients with ECOG PS ≥2 by line of treatment 71.6% 45 48 43 42 43 % % 20% 20% 40 20% 2016 2017 2018 48 49 35 38 33 38 34 33 32 33 33 33 32 s, s, 52.8% 39.1%

50 t t 44 26 27 26 29 27 30 27 49.1%

25 n n 10% 25 10% 25 10% 37.1% References e e i i

% 55.4% t t 47.0% 56.5% 37 a a 1. Stewart AK, et al. N Engl J Med 2015;372(2):142–52. 7. Chari A, et al. Blood 2017;130(8):974–81. s,

40 36 p p t

35 0% 0% 0% 50.6% f f n 33 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 58.5% 2. Dimopoulos MA, et al. Lancet Oncol 2016;17(1):27–38. 8. Lonial S, et al. N Engl J Med 2015;373(7):621–31. o o

e 57.0%

i 31 31

t 66.3% 3. Moreau P, et al. N Engl J Med 2016;374(17):1621–34. 9. Dimopoulos MA, et al. N Engl J Med 2018;379(19):1811–22. n n

a All patients DACH Non-DACH All patients DACH Non-DACH All patients DACH Non-DACH o o i i p 30 65.3% t t

4. Lonial S, et al. Lancet 2016;387(10027):1551–60. 10. Richardson PG, et al. Lancet Oncol 2019;20(6):781–94. r r f 18.1% 27.3% o o o Triplets Doublets Monotherapy 5. Dimopoulos MA, et al. N Engl J Med 2016;375(14):1319–31. 11. San Miguel J, et al. Lancet Oncol 2013;14(11):1055–66. p p n o 28.4% o 30.1% r r o 18.5% 6. Palumbo A, et al. N Engl J Med 2016;375(8):754–66. 12. Goldschmidt H, et al. Ann Hematol 2019;98(1):1–18. i 20 t

P P 19.5% r 18.0% 10.8% o • The proportions of patients treated with PI-based regimens as 2nd-, 3rd-, and ≥4th-line therapy increased from 2016 to 2018 (Figure 6), as did 42% 6.4% 42% p 28% 32% 20% 7.5%

o 26.2% r 10 the use of daratumumab-based regimens (Figure 7). 4.1% 16.6% 21.2%

P 15.4% Abbreviations 10.3% 11% 2.8% 13.1% 12.5% 13.7% 10.8% 11.5% − The increased use of PI-based regimens was driven by increased/earlier use of the novel PIs carfilzomib and ixazomib. 6.6% 3.5% ASCT, autologous stem cell transplantation; CHD, congestive heart disease; DACH, Germany, Austria, and Switzerland; Dd, daratumumab-dexamethasone; D-Pom-dex, 0 − These trends were more obvious in DACH, highlighting the impact of earlier access to modern treatment in these countries. Current 2L Current 3L Current 2L Current 3L Current 2L Current 3L Current 2L Current 3L Current 2L Current 3L Current 2L Current 3L daratumumab-pomalidomide-dexamethasone; DRd, daratumumab-lenalidomide-dexamethasone; DVd, daratumumab-bortezomib-dexamethasone; ECOG PS, Eastern 2nd line 3rd line ≥4th line 2,1062106 ptspts 826 pts 897 pts 395 pts 1,2091209 ptspts 431 pts 3,2003200 ptspts 1,5861586 ptspts 1,4321432 ptspts 702 pts 1,7681768 ptspts 884 pts Cooperative Oncology Group performance status; Elo, elotuzumab; Elo-Pom-dex, elotuzumab-pomalidomide-dexamethasone; Elo-Rd, elotuzumab-lenalidomide- dexamethasone; IMiD, immunomodulatory drug; IRd, ixazomib-lenalidomide-dexamethasone; ISS, International Staging System; Kd, carfilzomib-dexamethasone; KRd, Figure 6. Proportions of patients receiving PI-based treatment as 2nd-, 3rd-, and ≥4th-line therapy, by year and region iREAL total DACH Other iREAL total DACH Other • Among 2nd-line patients, >40% presented with ≥1 treatment-dependent comorbidity in 2016–2018, including hypertension in 23–27% and renal carfilzomib-lenalidomide-dexamethasone; L, line; mAb, monoclonal antibody; MM, multiple myeloma; N/A, not applicable; non-DACH, Belgium, France, Greece, Spain, impairment in 9–10% (Figure 3). 2nd-line regimens 3rd-line regimens ≥4th-line regimens and UK; PI, proteasome inhibitor; Pom, pomalidomide; Pom-dex, pomalidomide-dexamethasone; Pom-Vd, pomalidomide-bortezomib-dexamethasone; PS, performance − Comorbidity burden was similar at 3rd line and ≥4th line (data not shown). status; Pts, patients; R, lenalidomide; RCT, randomized controlled trial; Rd, lenalidomide-dexamethasone; RRMM, relapsed/refractory multiple myeloma; SCT, stem cell 60 60 60 • The rate of PI-based treatment as 1st-line therapy was 74%, 74%, and 75% in 2016, 2017, and 2018, respectively. • Cytogenetic risk was evaluated in 38%, 39%, and 42% of patients at initial diagnosis among those included in iREAL in 2016, 2017, and 2018, 54 transplantation; V, bortezomib. • Among these patients (Figure 9): respectively. 50 49 − Any PI-based to any IMiD-containing therapy was the most common treatment sequence in all years − The proportion of patients with high-risk cytogenetics, defined as del(17), t(4;14), or t(14;16), was 8%, 10%, and 10% of the total population, 50 50 47 50 Disclosures 43 44 − Any PI-based to any PI-based therapy use increased from 20% in 2016 to 28% in 2018 respectively. 42 This study was funded by Takeda Pharmaceuticals International AG. 41 − Any PI-based to any mAb-based therapy use also increased from 1% to 8%. 39 40 40 37 37 MM: travel grants from Takeda Vertrieb GmbH, Janssen, AbbVie, Celgene, Amgen; research funding from Takeda Vertrieb GmbH; membership on an entity's board of 40 36 35 35 35 35 35 35 34 Figure 3. Proportion of 2nd-line patients presenting with comorbidities 33 33 33 directors or advisory committees for Amgen. IVB: none. MP: membership on an entity's board of directors or advisory committees for Janssen, Celgene; speakers bureau 32 Figure 9. Treatment regimen sequences from 1st-line to 2nd-line therapy 30 30 for Janssen. BK: membership on an entity's board of directors or advisory committees for Amgen, Takeda; travel and registration for attendance at international medical 2016 2017 2018 42 43 45 30 30 27 30 28 Proportion of patients, % congress (ASH) for Janssen. AS: research funding for AbbVie, Amgen, Celgene, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda. EN: none. AZ, FG: 45 25 % 24 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 23 employment with Takeda Pharmaceuticals International AG. LK: research funding from Takeda, Amgen, BMS, Celgene, Janssen, Sanofi. HG: consultancy for Amgen, 40 22 s, 21

t 20 19 Celgene, Janssen, BMS, Sanofi, Adaptive Biotechnology, Takeda; grants from Amgen, Janssen, BMS, Sanofi, Chugai, John Hopkins University, n 35 e 20 17 17 i 20 20 16 2016 51 20 1 12 7 0 9 Dietmar-Hopp-Foundation; research funding from Amgen, Celgene, Janssen, BMS, Sanofi, Takeda, Chugai, Molecular Partners, MSD, Mundipharma, Novartis; honoraria t 27 15 15 15 a 30 14 25 13 13 13 13 13 p 12 12 from Celgene, Janssen, BMS, Sanofi, Chugai, Novartis, ArtTempi. 23 f 25 11 11 11 11 o 9 9 8 8 8 8 2017 43 26 4 13 6 1 7

n 7 7 20 10 10 6 10

o 5 5 i 4 4 4 t 12 12 12 4 4 Acknowledgements

r 3 3 3 15 11 11 11 10 2 2 o 9 8 9 1 1 1 1 1 1 1 p 10 6 7 6 6 7 0 2018 38 28 8 12 4 3 7 The authors would like to thank all investigators for their valuable contributions to the iREAL study. The authors also acknowledge Jenny Wilkinson and Steve Hill of o r 0 0 0 FireKite, an Ashfield company, part of UDG Healthcare plc, for writing assistance during the development of this poster, which was funded by Millennium Pharmaceuticals P 5 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 2016 2017 2018 Inc., and complied with Good Publication Practice 3 ethical guidelines (Battisti et al., Ann Intern Med 2015;163:461–4) and Renda Ferrari, PhD, (Millennium 0 PI to IMiD PI to PI PI to mAb IMiD to PI IMiD to IMiD IMiD to mAb Other* Pharmaceuticals, Inc.) for editorial support. Any Hypertension Diabetes CHD Renal impairment* Cardiac arrhythmias Cardiac insufficiency All patients DACH Non-DACH All patients DACH Non-DACH All patients DACH Non-DACH *‘Other’ 1st-line to 2nd-line sequences included PI-based to other regimen, IMiD-based to other regimen, and other regimen to any regimen; All PIs Carfilzomib Ixazomib *Renal impairment was per investigator assessment. other regimens included all non-PI-, non-IMiD-, non-mAb-containing regimens. Poster presentation at the 61st Annual Meeting of the American Society of Hematology (ASH), December 7–10, 2019, Orlando, FL, USA