Abstract
Introduction
To document the decision-making criteria physicians use when selecting regimens for second- and third-line therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) in Germany.
Methods
Experienced multiple myeloma (MM) physicians extracted data from medical records from 30 June to 8 September 2023 for patients who initiated approved second- and third-line therapy for MM in 2021. Regimens, most important treatment goal, and key reasons for prescribing were reported in addition to patient characteristics. All data were summarised descriptively.
Results
MM physicians (33 hospital-based, 16 office-based) with a median of 17 years of treatment experience extracted data from a total of 268 patient records (second-line, n = 170; third-line, n = 98). In second- and third-line, 17 and 16 different regimens were documented, respectively. The most utilized second-line regimens were: daratumumab (D), lenalidomide (R) and dexamethasone (d) (DRd 16.5%); carfilzomib (K), d and D (KdD 12.4%); Kd (11.2%); KRd; (10.0%); D, bortezomib (V) and d (DVd 9.4%); and V with cyclophosphamide (C) and d (VCd 7.1%). The main reasons for selecting the regimen were treatment effectiveness, patient characteristics/status, and relapse. Inducing deepest possible response and prolonging survival or symptom control were the most important treatment goals for triplet regimens. The main third-line regimens were: pomalidomide (P) and d (Pd 15.3%); DRd (13.3%); Rd (13.3%); elotuzumab (E) and Pd (EPd 12.2%); isatuximab (Isa) and Kd or KdD (10.2%); and ixazomib (I) and Rd (IRd 8.2%). The main reasons for selecting the regimens varied for third-line regimens but primarily focused on treatment effectiveness, patient characteristics/status, and prior therapy response or mechanism of action. The most important treatment goal was prolongation of survival.
Conclusion
The results suggest that in the absence of a single standard of care for RRMM, prescribers made patient-centred choices of regimens with efficacy as the main goal of therapy.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12325-025-03248-x.
Keywords: Multiple myeloma, Prescription preference, Second-line therapy, Third-line therapy, Treatment goals, Treatment reasons, Shared decision-making, Personalized care, Relapse and refractory
Key Summary Points
| Why carry out this study? |
| A wide variety of multidrug combinations are available for the treatment of relapsed and/or refractory multiple myeloma (RRMM), which allows physicians options for pursuing effective treatment aligned with individual patient treatment goals. |
| The aims of the current study were to gain a greater understanding of the decision-making criteria physicians use when selecting from approved regimens for second- and third-line therapy for MM in Germany, as well as to gain an understanding of patient characteristics and prior treatment history associated with regimen selection. |
| What was learned from this study? |
| For this rather young cohort of patients with RRMM, with a substantial representation of cytogenetically high-risk patients, experienced MM physicians selected a variety of second-line and third-line regimens with the most frequent primary treatment goals to induce the deepest possible response and to prolong progression-free survival and overall survival. Good efficacy was the primary reason for prescribing, followed by patient characteristics and selecting a regimen with another mode of action. |
| The study findings suggest that the management of RRMM is complex, and various multidrug therapies allow physicians to individualise treatment by making patient-centred decisions, keeping efficacy as the main goal of therapy. |
Introduction
Multiple myeloma (MM) represents one of the most common haematological malignancies, with an annual crude incidence rate of 8/100,000, increasing with age and accounting for 1.8% of cancer-related deaths in Germany [1]. MM remains uncured, and the primary treatment goal is disease control to prolong survival and improve quality of life (QoL) [2, 3]. Therapeutic options for newly diagnosed MM include combinations of a proteasome inhibitor (PI; bortezomib), immunomodulatory drugs (IMiD; lenalidomide), anti-CD38 antibodies (anti-CD38-ABs), cytostatics, glucocorticoids, and eligibility-dependent stem cell transplantation (SCT) [3–5].
After first-line treatment, the disease is characterised by periods of remission and relapse, with each period of remission generally shorter than the previous one [3, 6–8]. A wide variety of multidrug combinations are available for the treatment of relapsed and/or refractory MM (RRMM) [2, 4]. There are a large number of aspects to be considered for regimen selection, including transplant eligibility, prior therapy, length of initial remission, prior treatment response, cytogenetics, prognostic risk factors, toxicity, adverse events, patient living conditions, and patient QoL [5, 6, 9, 10].
The aims of the current study were to gain a greater understanding of the decision-making criteria physicians use when selecting approved regimens for second- and third-line therapy for MM in Germany, as well as to gain an understanding of patient characteristics and prior treatment history associated with regimens.
Methods
Study Design
We conducted a national, multicentre, retrospective, medical chart review of patients with RRMM who initiated second- or third-line therapy between January and December 2021. The index therapy line was defined as the initiation of second- or third-line therapy within the eligibility period (1 January–31 December 2021); the start of this therapy was the index date. The pre-index period spanned from the date of MM diagnosis and the index date. No post-index follow-up was documented. The study planned to include at least 150 patients from at least 25 physicians in Germany. Each physician could provide data from up to six medical records. Each physician completed a survey in addition to abstracting data from medical records. This was an exploratory, descriptive study with no hypotheses testing and thus sample size calculations were not performed. The determination of the number of physicians/medical records was based on feasibility estimates from fieldwork partners.
No identifiable protected health information was extracted during the study, and we consulted with the institutional review board (IRB) of Nordrhein (Düsseldorf). An official waiver of ethical approval was granted from the IRB of Nordrhein (Düsseldorf) on 31 May 2023.
Study Population
This study recruited experienced MM physicians practicing in hospitals and office-based centres in Germany. Participating haematologists or oncologists must have had at least 4 years of clinical experience, have been personally responsible for managing at least 10 patients per year who have RRMM, spend at least 60% of their time on patient care, and act as the main decision-maker for treatment of their patients with RRMM. MM physicians were recruited using a convenience sampling approach from panels of physicians who previously opted into research participation. The study sponsor was blinded to the identity of physicians. Physicians who accepted the email invitation and met the inclusion criteria were those who participated in the study.
The selection criteria included patients with MM who were aged 18 years or older and who had initiated an approved second- or third-line therapy for MM within the eligibility period. If a participant initiated both second- and third-line therapy during 2021, they were included in the third-line group. MM physicians extracted data from 30 June to 8 September 2023 from medical patient records using an electronic data collection form (eDCF) designed specifically for this study. The eDCF was tested by 2 MM physicians in Germany to ensure its usability and completeness before launching data collection.
Study Objectives and Assessments
The primary study objective was to document the regimens selected and the decision-making criteria physicians used when selecting regimens for second- and third-line therapy for MM in Germany. Secondary objectives were to describe demographics, clinical characteristics and treatment history of patients (including re-treatment with an anti-CD38-AB-containing regimen) receiving each type of second- or third-line therapy for MM in Germany, as well as physician characteristics.
Primary and secondary treatment goals were selected from a list of seven options and the top five most important reasons for prescribing therapies were selected from a list of 28 options (see Supplementary Table S1). This selection was conducted for the medical record data abstraction (based on actual patient data) and the physician survey (based on physician reports of their general practice).
Statistical Analyses
All data were summarised descriptively using mean values, medians, ranges, and standard deviations for continuous variables of interest and frequency distributions for categorical variables. Analyses were conducted using Statistical Analysis System software (version 9.4).
Results
Sample Characteristics
A total of 49 well-experienced and mainly hospital-based physicians participated in the study (Table 1). They extracted a total of 268 medical records, of which 170 patients (63.4%) initiated second-line therapy and 98 patients (36.6%) third-line therapy during 2021. Table 2 shows the patient demographic and clinical characteristics, overall and by index therapy line.
Table 1.
Physician characteristics
| Characteristic | Physicians (N = 49) |
|---|---|
| Age, mean (SD), years | 50.5 (8.0) |
| Sex, n (%) | |
| Male | 37 (75.5) |
| Female | 10 (20.4) |
| Missing | 2 (4.1) |
| Primary medical specialty, n (%) | |
| Haematology/oncology | 42 (85.7) |
| Medical oncology | 5 (10.2) |
| Haematology | 2 (4.1) |
| Geographic location, n (%) | |
| Bremen; Hamburg; Niedersachsen; Schleswig-Holstein | 11 (22.4) |
| Nordrhein-Westfalen | 10 (20.4) |
| Hessen; Rheinland-Pfalz; Saarland | 10 (20.4) |
| Baden-Württemberg; Bayern | 15 (30.6) |
| Berlin; Brandenburg; Mecklenburg-Vorpommern; Sachsen; Sachsen-Anhalt; Thüringen | 3 (6.1) |
| Primary practice setting, n (%) | |
| Hospital-based | 33 (67.3) |
| Office-based | 16 (32.7) |
| Size of primary practice setting, n (%) | |
| Individual | 4 (8.2) |
| Small/intermediate (2–9 haematologists/oncologists) | 28 (57.1) |
| Large (10 or more haematologists/oncologists) | 17 (34.7) |
| No. of years in practice since full qualification, mean (SD) | 17.2 (6.0) |
| Approximate no. of patients with MM managed in a typical month,a mean (SD) | 36.1 (22.7) |
SD standard deviation
aIncluding new diagnoses, treatment initiation, and follow-up care
Table 2.
Patient demographic and clinical characteristics
| Characteristic | Total sample (N = 268) |
Initiated second-line therapy in 2021 (n = 170) |
Initiated third-line therapy in 2021 (n = 98) |
|---|---|---|---|
| Age at initiation of index therapy line, mean (SD), years | 67.2 (9.4) | 66.9 (9.4) | 67.6 (9.3) |
| Sex, n (%) | |||
| Male | 158 (59.0) | 105 (61.8) | 53 (54.1) |
| Female | 109 (40.7) | 64 (37.6) | 45 (45.9) |
| Intersex | 1 (0.4) | 1 (0.6) | 0 |
| MM subtype among at least 5% of the overall sample, n (%) | |||
| IgG kappa | 108 (40.3) | 68 (40.0) | 40 (40.8) |
| IgG lambda | 59 (22.0) | 36 (21.2) | 23 (23.5) |
| IgA kappa | 24 (9.0) | 13 (7.6) | 11 (11.2) |
| IgM kappa | 14 (5.2) | 6 (3.5) | 8 (8.2) |
| IgA lambda | 13 (4.9) | 9 (5.3) | 4 (4.1) |
| ECOG performance status upon initiation of second- or third-line therapy for MM, n (%) | |||
| 0 | 26 (9.7) | 14 (8.2) | 12 (12.2) |
| 1 | 121 (45.1) | 84 (49.4) | 37 (37.8) |
| 2 | 93 (34.7) | 58 (34.1) | 35 (35.7) |
| 3 | 22 (8.2) | 8 (4.7) | 14 (14.3) |
| 4 | 0 | 0 | 0 |
| Unknown | 6 (2.2) | 6 (3.5) | 0 |
| ISS stage upon initiation of second- or third-line therapy, n (%) | |||
| I | 28 (10.4) | 22 (12.9) | 6 (6.1) |
| II | 101 (37.7) | 73 (42.9) | 28 (28.6) |
| III | 137 (51.1) | 73 (42.9) | 64 (65.3) |
| Unknown | 2 (0.7) | 2 (1.2) | 0 |
| History of at least 1 bone lesion, n (%) | 198 (73.9) | 119 (70.0) | 79 (80.6) |
| Clinical signs and symptoms prior to initiation of second- or third-line therapy for MMa n (%) | |||
| Anaemia | 176 (65.7) | 119 (70.0) | 57 (58.2) |
| Bone pain | 169 (63.1) | 102 (60.0) | 67 (68.4) |
| Increase in paraproteins | 123 (45.9) | 84 (49.4) | 39 (39.8) |
| Hypercalcaemia | 99 (36.9) | 54 (31.8) | 45 (45.9) |
| Renal dysfunction/insufficiency | 99 (36.9) | 58 (34.1) | 41 (41.8) |
| High-risk cytogeneticsb, n (%) | 91 (43.3) | 53 (42.7) | 38 (44.2) |
| Eligible for transplant in prior-line therapy, n (%) | |||
| Yes | 64 (23.9) | 53 (31.2) | 11 (11.2) |
| No | 204 (76.1) | 117 (68.8) | 87 (88.8) |
ECOG Eastern Cooperative Oncology Group, Ig immunoglobulin G, ISS International Staging System, MM multiple myeloma, SD standard deviation
aAmong at least 10% of the total sample
bCytogenetically high-risk MM is defined by the presence of t(4;14), t(14;16), del(17p13), or > 3 copy(1q21) mutations; proportions are based on the denominator of patients who were tested for cytogenetic abnormalities (n = 210; n = 124 second-line and n = 86 third-line)
At the start of index therapy, patients had a median age of 68.4 years, were predominantly male (59%), had good PS of 80% with Eastern Cooperative Oncology Group (ECOG)-PS of 1 or 2, and bone lesion (74%), anaemia (66%), and bone pain (63%) were common. International Staging System (ISS) stage upon index therapy initiation was primarily II (37.7%) or III (51.1%). Cytogenetic testing was available for 78%, of which 43% had high-risk cytogenetics [defined as the presence of t(4;14), t(14;16), del(17p13), or > 3 copy(1q21) mutations].
Treatment Patterns and Decision-Making Criteria
Patients Who Initiated Second-Line Therapy in 2021
Pre-index Therapy
Of the 170 patients who received second-line therapy, 53 (31.2%) were eligible for transplant during first-line therapy and 117 (68.8%) were not. Most patients who were transplant-eligible during first-line therapy received a PI-including regimen in the first line (94.2%; predominantly bortezomib). Time to relapse from initiation of first-line therapy was a median of 24.2 months [mean (SD): 27.2 (20.3) months]. Most patients who were transplant-ineligible during first-line therapy received IMiD-including (61.5%; predominantly lenalidomide) or PI-including (53.0%; predominantly bortezomib) regimens in the first line (25.6% received PI + IMiD-based regimens). Time to relapse from initiation of first-line therapy was a median of 13.1 months [mean (SD): 23.0 (51.7) months].
First-line therapy was primarily discontinued due to completion of planned treatment (38.8%) or progressive disease (32.9%). Median time to next treatment from initiation of first-line therapy was 24.7 months for patients who were transplant-eligible during first-line therapy and 16.8 months for those who were not.
Index Therapy
A total of 17 different regimens were prescribed for second-line index therapy, most commonly daratumumab (D) with lenalidomide ®) and dexamethasone (d) [DRd 16.5% (28/170)], carfilzomib (K) with d and D [KdD 12.4% (21/170)], Kd [11.2% (19/170)], KRd [10.0% (17/170)], D with bortezomib (V) and d [DVd 9.4% (16/170)], and V with cyclophosphamide C) and d [VCd 7.1% ([12/170)] (Supplementary Table S2).
The proportions of regimens for second-line index therapy concur with those from the physician survey. The most common regimen physicians stated they prescribed during second-line therapy in 2021 was DRd, independent of whether patients were eligible for transplant (31%) or ineligible for transplant (27%). The next most common regimens were KRd (25%), DVd (20%), and KdD (18%) for transplant-eligible patients and KRd (16%), Kd (16%), DVd (16%), and KdD (14%) for transplant-ineligible patients.
Patients receiving Kd and KRd were slightly older than those receiving DRd, KdD, DVd, or VCd (Table 3 and Supplementary Table S3). Patients who received VCd had the shortest time to relapse from first-line therapy, and patients receiving Kd had the longest. At least a third of patients receiving DRd, KdD, Kd, and KRd had high-risk cytogenetics, but these were not common among patients receiving DVd or VCd. Patients receiving DRd and VCd were commonly treated by office-based physicians. No differences in clinical signs and symptoms before initiation of index therapy or comorbidities were evident among the different regimens. Re-treatment with an anti-CD38-AB-containing regimen was uncommon (range across regimens: 0–3 participants).
Table 3.
Key characteristics by main regimens used in second-line therapy initiated in 2021
| DRd (n = 28, 16.5%) |
KdD (n = 21, 12.4%) |
Kd (n = 19, 11.2%) |
KRd (n = 17, 10.0%) |
DVd (n = 16, 9.4%) |
VCd (n = 12, 7.1%) |
|
|---|---|---|---|---|---|---|
| Age at regimen initiation, mean (SD), years | 67.9 (7.9) | 59.9 (11.2) | 72.7 (8.1) | 70.4 (6.3) | 66.2 (7.9) | 61.2 (9.4) |
| Sex, n (%) | ||||||
| Female | 11 (39.3) | 6 (28.6) | 6 (31.6) | 4 (23.5) | 6 (37.5) | 4 (33.3) |
| Male | 17 (60.7) | 14 (66.7) | 13 (68.4) | 13 (76.5) | 10 (62.5) | 8 (66.7) |
| Intersex | 0 | 1 (4.8) | 0 | 0 | 0 | 0 |
| Time to relapse from initiation of first-line therapy, mean (SD), months | 24.3 (14.8) | 36.6 (54.7) | 49.7 (110.8) | 18.3 (12.9) | 24.2 (14.2) | 6.4 (7.5) |
| Time to next treatment from initiation of first-line therapy, mean (SD), months | 26.4 (14.1) | 38.7 (54.6) | 54.1 (118.4) | 21.2 (12.5) | 25.9 (13.7) | 15.0 (14.9) |
| Best response to first-line therapy, n (%) | ||||||
| Stringent complete response | 9 (32.1) | 5 (23.8) | 0 | 0 | 2 (12.5) | 0 |
| Complete response | 7 (25.0) | 2 (9.5) | 2 (10.5) | 5 (29.4) | 6 (37.5) | 2 (16.7) |
| Very good partial response | 10 (35.7) | 9 (42.9) | 9 (47.4) | 10 (58.8) | 5 (31.3) | 5 (41.7) |
| Partial response | 2 (7.1) | 5 (23.8) | 4 (21.1) | 1 (5.9) | 1 (6.3) | 0 |
| Minimal response | 0 | 0 | 1 (5.3) | 1 (5.9) | 1 (6.3) | 0 |
| Stable disease | 0 | 0 | 2 (10.5) | 0 | 1 (6.3) | 5 (41.7) |
| Progressive disease | 0 | 0 | 1 (5.3) | 0 | 0 | |
| ECOG performance status upon initiation of regimena, n (%) | ||||||
| 0 | 2 (7.1) | 6 (28.6) | 1 (5.3) | 1 (5.9) | 0 | 0 |
| 1 | 17 (60.7) | 7 (33.3) | 7 (36.8) | 9 (52.9) | 8 (50.0) | 10 (83.3) |
| 2 | 9 (32.1) | 7 (33.3) | 7 (36.8) | 7 (41.2) | 6 (37.5) | 2 (16.7) |
| 3 | 0 | 1 (4.8) | 2 (10.5) | 0 | 0 | 0 |
| 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| ISS stage upon initiation of regimen, n (%) | ||||||
| I | 3 (10.7) | 4 (19.0) | 3 (15.8) | 0 | 1 (6.3) | 4 (33.3) |
| II | 10 (35.7) | 8 (38.1) | 8 (42.1) | 7 (41.2) | 8 (50.0) | 6 (66.7) |
| III | 15 (53.6) | 9 (42.9) | 7 (36.8) | 10 (58.8) | 7 (43.8) | 0 |
| Unknown | 0 | 0 | 1 (5.3) | 0 | 0 | 0 |
| High-risk cytogeneticsb, n (%) | 11 (39.3) | 9 (42.9) | 6 (31.6) | 6 (35.3) | 3 (18.8) | 1 (8.3) |
| Were eligible for transplant in first-line therapy, n (%) | 13 (46.4) | 11 (52.4) | 1 (5.3) | 6 (35.3) | 4 (25.0) | 2 (16.7) |
| Received treatment with anti-CD38-AB-containing regimen in first-line therapy, n (%) | 0 | 2 (9.5) | 3 (15.8) | 3 (17.6) | 1 (6.3) | 1 (8.3) |
| Prescribing physician’s primary practice setting, n (%) | ||||||
| Hospital-based | 15 (53.6) | 17 (81.0) | 15 (78.9) | 15 (88.2) | 11 (68.8) | 6 (50.0) |
| Office-based | 13 (46.4) | 4 (19.0) | 4 (21.1) | 2 (11.8) | 5 (31.3) | 6 (50.0) |
| Approximate no. of patients with MM managed in a typical month by the prescribing physician, mean (SD) | 30.4 (11.3) | 51.3 (28.6) | 42.2 (30.6) | 33.4 (24.6) | 38.1 (17.5) | 55.2 (36.5) |
Data from the remaining regimens is shown in supplementary Table S2
Anti-CD38-AB anti-CD38 antibody, DRd daratumumab/lenalidomide/dexamethasone (d), DVd daratumumab/bortezomib/dexamethasone, ECOG Eastern Cooperative Oncology Group, Kd carfilzomib/dexamethasone, KdD carfilzomib/dexamethasone/daratumumab, KRd carfilzomib/lenalidomide/dexamethasone, ISS International Staging System, MM multiple myeloma, SD standard deviation, VCd bortezomib/cyclophosphamide/dexamethasone
a0 = normal activity; 1 = symptoms demonstrated, but the patient remains ambulatory and able to perform self-care; 2 = ambulatory > 50% of the time and requires occasional assistance; 3 = ambulatory < 50% of the time and requires nursing care; 4 = bedridden
bCytogenetically high-risk MM is defined by the presence of t(4;14), t(14;16), del(17p13), or > 3 copy(1q21) mutations
Treatment sequencing of second-line index therapy based on prior therapy is presented in Fig. 1. Patients who received a PI in the first line often received re-treatment with a second PI [e.g. KdD, isatuximab (Isa) with K and d (IsaKd), KRd, DVd, V with R and d (VRd)]. Only a few patients received an anti-CD38-AB-containing regimen in the first line. Patients who did not receive an anti-CD38-AB in the first line often received one in the second line (e.g. DRd, KdD, IsaKd, DVd). When patients were treated with an IMiD-including combination in the first line, nearly half of the patients received an IMiD-including re-treatment in the second line, and the other half experienced a mode of action change to PI-including combinations (Fig. 1).
Fig. 1.
Treatment sequencing based on transplant receipt and therapy type in first line for regimens for second-line therapy for MM during 2021; numbers in parentheses represent numbers of patients; Other refers to patients who were transplant-ineligible and/or high dose therapy and further therapy is unknown. Among the KdD and IsaKd group, 21 patients received KdD and 4 received IsaKd. CD38+ containing an anti-CD38-antibody, CD38– not containing an anti-CD38– antibody, D daratumumab monotherapy, DPd daratumumab/pomalidomide/dexamethasone, DRd daratumumab/lenalidomide/dexamethasone, DVd daratumumab/bortezomib/dexamethasone, ERd elotuzumab/lenalidomide/dexamethasone, IMiD+ containing immunomodulatory drug, IMiD– not containing immunomodulatory drug, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone, K+ containing carfilzomib, K– not containing carfilzomib, Kd carfilzomib/dexamethasone, KdD carfilzomib/daratumumab/dexamethasone, KRd carfilzomib/lenalidomide/dexamethasone, MM multiple myeloma, PI+ containing proteasome inhibitor, PI– not containing proteasome inhibitor, PVd pomalidomide/bortezomib/dexamethasone, RCd lenalidomide/cyclophosphamide/dexamethasone, Rd lenalidomide/dexamethasone, TE transplant eligible, TI transplant ineligible, VAd bortezomib/doxorubicin/dexamethasone, VCd bortezomib/cyclophosphamide/dexamethasone, Vd bortezomib/dexamethasone, VRd bortezomib/lenalidomide/dexamethasone
The most common reasons for prescribing DRd and DVd were good efficacy and fitness; for KRd, good efficacy, fitness, and disease risk/stage; for KdD, unfavourable cytogenetics, performance status, and symptomatic relapse; for Kd, age, good efficacy, and fitness; and for VCd, symptomatic relapse, good efficacy, and QoL (Fig. 2).
Fig. 2.
Reasons for prescribing second-line regimens. D daratumumab, DPd daratumumab/pomalidomide/dexamethasone, DRd daratumumab/lenalidomide/dexamethasone, DVd daratumumab/bortezomib/dexamethasone, ERd elotuzumab/lenalidomide/dexamethasone, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone, Kd carfilzomib/dexamethasone, KdD carfilzomib/daratumumab/dexamethasone, KRd carfilzomib/lenalidomide/dexamethasone, PVd pomalidomide/bortezomib/dexamethasone, RCd lenalidomide/cyclophosphamide/dexamethasone, Rd lenalidomide/dexamethasone, VAd bortezomib/doxorubicin/dexamethasone, VCd bortezomib/cyclophosphamide/dexamethasone, Vd bortezomib/dexamethasone, VRd bortezomib/lenalidomide/dexamethasone
The most frequently identified most important treatment goals for DRd and KdD were prolongation of progression-free survival (PFS) and induction of deepest possible response (Fig. 3). For Kd, these were prolongation of overall survival (OS), symptom control, and recovery of QoL. For KRd and DVd, the most important goals were induction of the deepest possible response and prolongation of OS. For VCd, these were induction of deepest possible response and symptom control.
Fig. 3.
Most and second most important treatment goals for most common second-line regimens. D daratumumab, DPd daratumumab/pomalidomide/dexamethasone, DPR deepest possible response, DRd daratumumab/lenalidomide/dexamethasone, DVd daratumumab/bortezomib/dexamethasone, ERd elotuzumab/lenalidomide/dexamethasone, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone, Kd carfilzomib/dexamethasone, KdD carfilzomib/daratumumab/dexamethasone, KRd carfilzomib/lenalidomide/dexamethasone, OS overall survival, PFS progression-free survival, PVd pomalidomide/bortezomib/dexamethasone, QoL quality of life, RCd lenalidomide/cyclophosphamide/dexamethasone, Rd lenalidomide/dexamethasone, VAd bortezomib/doxorubicin/dexamethasone, VCd bortezomib/cyclophosphamide/dexamethasone, Vd bortezomib/dexamethasone, VRd bortezomib/lenalidomide/dexamethasone
Patients Who Initiated Third-Line Therapy in 2021
Pre-index Therapy
A total of 29 of 98 patients (29.6%) were eligible for transplant during first-line therapy and 69 (70.4%) were not; 11 patients (11.2%) were transplant-eligible during second-line therapy and 87 (88.8%) were not.
For patients who were transplant-eligible during first-line therapy, time to relapse was a median of 23.5 months [mean (SD): 38.0 (48.6) months] from initiation of first-line therapy and 3.6 months [mean (SD): 12.1 (14.2) months] from initiation of second-line therapy.
For patients who were transplant-ineligible during first- and second-line therapies, time to relapse was a median of 15.4 months [mean (SD): 16.9 (10.2) months] from initiation of first-line therapy and 19.8 months [mean (SD): 20.1 (17.1) months] from initiation of second-line therapy.
First-line therapy was primarily discontinued due to completion of planned treatment (70.4%); for second-line treatment, discontinuation occurred because of completion of planned treatment (61.2%) or progressive disease (25.5%). Median time to next treatment from initiation of first-line therapy was 26.6 months for patients who were transplant-eligible during first-line therapy and 16.0 months for those who were not. Median time to next treatment from initiation of second-line therapy was 6.9 months for patients who were transplant-eligible during second-line therapy and 20.6 months for those who were not.
Index Therapy
Of a total of 16 different regimens initiated in third-line therapy during 2021, the most prescribed regimens were pomalidomide (P) and d [Pd 15.3% (15/98)]; DRd [13.3% (13/98)]; Rd [13.3% (13/98)]; elotuzumab (E) and Pd [EPd 12.2% (12/98)]; IsaKd or KdD [10.2% (10/98]; IsaKd n = 8, KdD n = 2); and ixazomib (I) and Rd [IRd 8.2% (8/98)] (Supplementary Table S4).
The proportions of regimens for third-line index therapy are slightly different from those given in the physician survey. The most common regimen physicians stated they typically prescribed to transplant-eligible patients during third-line therapy in 2021 was KdD (20%) and the second most common were DRd, DVd, and EPd (each 18%). For transplant-ineligible patients, the most common third-line regimen was EPd (25%), and the second most common regimens were Pd and IRd (each 16%).
Patients receiving Pd, DRd, EPd, and IRd were slightly older than those receiving Rd or IsaKd/KdD (Table 4 and Supplementary Table S5). Patients receiving DRd or KdD had the longest time to relapse from first-line therapy. Transplant receipt in the first line was most common among patients receiving IsaKd and least common among patients receiving Panobinostat (Pano) with Vd (PanoVd), Kd, IRd, or Rd. Patients receiving Pd or IsaKd were always treated by hospital-based physicians; patients receiving DRd were most commonly treated by office-based physicians. No differences in clinical signs and symptoms before initiation of index therapy or comorbidities were evident among the different regimens. Re-treatment with an anti-CD38-AB-containing regimen was uncommon.
Table 4.
Key characteristics by main regimens used in third-line therapy initiated in 2021
| Pd (n = 15, 15.3%) |
DRd (n = 13, 13.3%) |
Rd (n = 13, 13.3%) |
EPd (n = 12, 12.2%) |
IsaKd (n = 8, 8.2%) |
IRd (n = 8, 8.2%) |
|
|---|---|---|---|---|---|---|
| Age at regimen initiation, mean (SD), years | 72.0 (6.8) | 70.9 (7.8) | 59.9 (12.0) | 70.8 (7.5) | 62.7 (6.0) | 70.5 (9.4) |
| Sex, n (%) | ||||||
| Female | 9 (60.0) | 5 (38.5) | 6 (46.2) | 5 (41.7) | 1 (12.5) | 3 (37.5) |
| Male | 6.40.0) | 8 (61.5) | 7 (53.8) | 7 (58.3) | 7 (87.5) | 5 (62.5) |
| Intersex | 0 | 0 | 0 | 0 | 0 | 0 |
| Time to relapse from initiation of first-line therapy, mean (SD), months | 36.0 (59.6) | 35.0 (25.0) | 16.0 (6.9) | 21.9 (12.6) | 19.0 (10.0) | 16.1 (10.4) |
| Time to next treatment from initiation of first-line therapy, mean (SD), months | 37.4 (60.5) | 35.5 (25.0) | 16.0 (7.2) | 23.1 (12.3) | 19.5 (10.2) | 17.4 (11.3) |
| Time to relapse from initiation of second-line therapy, mean (SD), months | 29.7 (23.5) | 18.1 (10.4) | 16.2 (8.9) | 20.1 (19.5) | 16.2 (9.7) | 13.4 (11.1) |
| Time to next treatment from initiation of second-line therapy, mean (SD), months | 30.7 (25.5) | 18.8 (10.5) | 16.7 (8.7) | 20.8 (19.3) | 17.0 (9.1) | 14.2 (11.0) |
| Best response to first-line therapy, n (%) | ||||||
| Stringent complete response | 1 (6.7) | 3 (23.1) | 0 | 1 (8.3) | 1 (12.5) | 0 |
| Complete response | 1 (6.7) | 5 (38.5) | 1 (7.7) | 5 (41.7) | 2 (25.0) | 0 |
| Very good partial response | 6 (40.0) | 2 (15.4) | 7 (53.8) | 4 (33.3) | 0 | 5 (62.5) |
| Partial response | 7 (46.7) | 1 (7.7) | 2 (15.4) | 1 (8.3) | 4 (50.0) | 2 (25.0) |
| Minimal response | 0 | 2 (15.4) | 0 | 0 | 0 | 0 |
| Stable disease | 0 | 0 | 2 (15.4) | 0 | 1 (12.5) | 0 |
| Progressive disease | 0 | 0 | 0 | 1 (8.3) | 0 | 1 (12.5) |
| Unknown | 0 | 0 | 1 (7.7) | 0 | 0 | 0 |
| Best response to second-line therapy, n (%) | ||||||
| Stringent complete response | 0 | 1 (7.7) | 0 | 1 (8.3) | 0 | 0 |
| Complete response | 1 (6.7) | 3 (23.1) | 1 (7.7) | 7 (58.3) | 2 (25.0) | 0 |
| Very good partial response | 6 (40.0) | 5 (38.5) | 4 (30.8) | 2 (16.7) | 0 | 0 |
| Partial response | 8 (53.3) | 2 (15.4) | 4 (30.8) | 1 (8.3) | 5 (62.5) | 4 (50.0) |
| Minimal response | 0 | 2 (15.4) | 1 (7.7) | 1 (8.3) | 0 | 2 (25.0) |
| Stable disease | 0 | 0 | 2 (15.4) | 0 | 1 (12.5) | 0 |
| Progressive disease | 0 | 0 | 0 | 0 | 0 | 2 (25.0) |
| Unknown | 0 | 0 | 1 (7.7) | 0 | 0 | 0 |
| ECOG performance status upon initiation of regimena, n (%) | ||||||
| 0 | 0 | 3 (23.1) | 3 (23.1) | 1 (8.3) | 1 (12.5) | 0 |
| 1 | 1 (6.7) | 9 (69.2) | 4 (30.8) | 6 (50.0) | 3 (37.5) | 4 (50.0) |
| 2 | 10 (66.7) | 1 (7.7) | 4 (30.8) | 5 (41.7) | 1 (12.5) | 2 (25.0) |
| 3 | 4 (26.7) | 0 | 2 (15.4) | 0 | 3 (37.5) | 2 (25.0) |
| 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| ISS stage at initiation of regimen, n (%) | ||||||
| I | 0 | 2 (15.4) | 1 (7.7) | 1 (8.3) | 1 (12.5) | 0 |
| II | 2 (13.3) | 4 (30.8) | 5 (38.5) | 5 (41.7) | 2 (25.0) | 1 (12.5) |
| III | 13 (86.7) | 7 (53.8) | 7 (53.8) | 6 (50.0) | 5 (62.5) | 7 (87.5) |
| Unknown | 0 | 0 | 0 | 0 | 0 | 0 |
| High-risk cytogeneticsb, n (%) | 5 (33.3) | 4 (30.8) | 5 (38.5) | 4 (33.3) | 3 (37.5) | 4 (50.0) |
| Were eligible for transplant in first line, n (%) | 4 (26.7) | 5 (38.5) | 1 (7.7) | 4 (33.3) | 4 (50.0) | 1 (12.5) |
| Received treatment with anti-CD38-AB-containing regimen in first-line therapy, n (%) | 1 (6.7) | 1 (7.7) | 0 | 8 (66.7) | 2 (25.0) | 2 (25.0) |
| Received treatment with anti-CD38-AB-containing regimen in second-line therapy, n (%) | 10 (66.7) | 1 (7.7) | 4 (30.8) | 3 (25.0) | 3 (37.5) | 2 (25.0) |
| Prescribing physician’s primary practice setting, n (%) | ||||||
| Hospital-based | 15 (100.0) | 4 (30.8) | 7 (53.8) | 6 (50.0) | 8 (100.0) | 7 (87.5) |
| Non-hospital-based | 0 | 9 (69.2) | 6 (46.2) | 6 (50.0) | 0 | 1 (12.5) |
| Approximate no. of patients with MM managed in a typical month by the prescribing physician, mean (SD) | 52.9 (15.3) | 34.3 (28.7) | 37.2 (23.0) | 37.8 (29.3) | 45.0 (19.8) | 38.3 (11.1) |
Data from the remaining regimens is shown in supplementary Table S4
Anti-CD38-AB anti-CD38 antibody, DRd daratumumab/lenalidomide/dexamethasone, ECOG Eastern Cooperative Oncology Group, EPd elotuzumab/pomalidomide/dexamethasone, ISS International Staging System, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone, MM multiple myeloma, Pd pomalidomide/dexamethasone, Rd lenalidomide/dexamethasone, SD standard deviation
a0 = normal activity; 1 = symptoms demonstrated, but the patient remains ambulatory and able to perform self-care; 2 = ambulatory > 50% of the time and requires occasional assistance; 3 = ambulatory < 50% of the time and requires nursing care; 4 = bedridden
bCytogenetic high-risk MM is defined by the presence of t(4;14), t(14;16), del(17p13), or > 3 copy(1q21) mutations
Treatment sequencing across the first, second, and third (index) lines of therapy according to transplant eligibility and regimens received is shown in Fig. 4. Similar to the findings for second-line index therapy (Fig. 1), patients who received a PI- or IMiD-including combination in the first line often received re-treatment with a second PI or IMiD. Only a few patients received an anti-CD38-AB-containing regimen in the first line or in the second line. Patients who did not receive an anti-CD38-AB in the prior therapy often received an anti-CD38-AB in the third line (e.g. DRd, KdD, IsaKd). When patients were treated with an IMiD-including combination in the second line, patients often received an IMiD-including re-treatment in the third line (e.g. Pd, Rd, EPd) (Fig. 4).
Fig. 4.
Treatment sequencing based on transplant receipt and therapy type in first and second lines for regimens for third-line therapy for MM during 2021: Panel A grouped by PI use; Panel B grouped by anti-CD38-antibody use; Panel C grouped by IMiD use; numbers in parentheses represent numbers of patients, Other refers to patients who were transplant-ineligible and/or high dose therapy and further therapy is unknown. Among the KdD and IsaKd group, 2 patients received KdD and 8 received IsaKd. 1L first line, 2L second line, 3L third line, CD38+ containing an anti-CD38-antibody, CD38– not containing an anti-CD38-antibody, D daratumumab monotherapy, DRd daratumumab/lenalidomide/dexamethasone, DVd daratumumab/bortezomib/dexamethasone, EPd elotuzumab/pomalidomide/dexamethasone, ERd elotuzumab/lenalidomide/dexamethasone, IMiD+ containing immunomodulatory drug, IMiD– not containing immunomodulatory drug, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone; K+ containing carfilzomib, K– not containing carfilzomib, Kd carfilzomib/dexamethasone, KdD carfilzomib/daratumumab/dexamethasone, KRd carfilzomib/lenalidomide/dexamethasone, MM multiple myeloma, PanoVd panobinostat/bortezomib/dexamethasone, Pd pomalidomide/dexamethasone, PI+ containing proteasome inhibitor, PI– not containing proteasome inhibitor, PVd pomalidomide/bortezomib/dexamethasone, Rd lenalidomide/dexamethasone, TE transplant eligible, TI transplant ineligible, VCd bortezomib/cyclophosphamide/dexamethasone, VRd bortezomib/lenalidomide/dexamethasone
The most common reasons for prescribing Pd and Rd were good efficacy, age, and long duration of response (Fig. 5). For DRd, these were good efficacy, fitness, and other mode of action. For EPd, QoL, other mode of action, age, deep response to prior therapy, and long duration of response; for IsaKd or KdD, age, long duration of response, and performance status; and for IRd, disease risk/stage and age.
Fig. 5.
Reasons for prescribing third-line regimens. D daratumumab, DRd daratumumab/lenalidomide/dexamethasone, DVd daratumumab/bortezomib/dexamethasone, EPd elotuzumab/pomalidomide/dexamethasone, ERd elotuzumab/lenalidomide/dexamethasone, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone, Kd carfilzomib/dexamethasone, KdD carfilzomib/daratumumab/dexamethasone, KRd carfilzomib/lenalidomide/dexamethasone, PanoVd panobinostat/bortezomib/dexamethasone, Pd pomalidomide/dexamethasone, PVd pomalidomide/bortezomib/dexamethasone, Rd lenalidomide/dexamethasone, VCd bortezomib/cyclophosphamide/dexamethasone, VRd bortezomib/lenalidomide/dexamethasone
The most frequently identified most important treatment goals were primarily prolongation of PFS and OS (Fig. 6).
Fig. 6.
Most and second most important treatment goals for most common third-line regimens. D daratumumab, DPR deepest possible response, DRd daratumumab/lenalidomide/dexamethasone, DVd daratumumab/bortezomib/dexamethasone, EPd elotuzumab/pomalidomide/dexamethasone, ERd elotuzumab/lenalidomide/dexamethasone, IRd ixazomib/lenalidomide/dexamethasone, IsaKd isatuximab/carfilzomib/dexamethasone, Kd carfilzomib/dexamethasone, KdD carfilzomib/daratumumab/dexamethasone, KRd carfilzomib/lenalidomide/dexamethasone, OS overall survival, PanoVd panobinostat/bortezomib/dexamethasone, Pd pomalidomide/dexamethasone, PFS progression-free survival, PVd pomalidomide/bortezomib/dexamethasone, QoL quality of life, Rd lenalidomide/dexamethasone, VCd bortezomib/cyclophosphamide/dexamethasone, VRd bortezomib/lenalidomide/dexamethasone
Discussion
To our knowledge, this is the first published real-world evidence study asking physicians to state the most important treatment goals and primary reasons for selecting later-line regimens for MM in Germany. We found that a variety of regimens were selected, the most frequent primary treatment goals being induction of deepest possible response and prolongation of PFS and OS, especially amongst triplet regimens. Reasons for selecting specific regimens varied, but good efficacy of the regimen was most frequently noted. Also commonly considered were patient characteristics (especially age and health status), tolerability/toxicity profile of the regimen, and patient QoL. For third-line regimens, the regimen offering a different mode of action to prior treatment was also commonly noted, alongside long duration of response to prior treatment.
Patients were on average aged less than 70 years upon initiation of second- or third-line, which is slightly younger than previously reported for later-line therapy [8]. This finding may reflect the disproportion of hospital-based physicians within our sample. The performance status measured with ECOG-PS or Karnofsky was also one of the baseline characteristics in our study. Overall, not all regimens are equally suitable for a patient whose fitness state needs to be accounted for when assessing the performance status to select a suitable regimen. Half of the patient population in our study were classified in ISS stage III, which is the stage associated with the poorest outcomes [11]. More patients receiving third-line therapy were in ISS stage III than patients receiving second-line therapy, which may reflect deterioration in disease status with each treatment line. This finding may also be an artifact of selection bias, where physicians may have selected higher-risk patients. However, at initial MM diagnosis, a smaller proportion of patients in the third-line therapy cohort were in stage III disease than were patients in the second-line cohort, which may reflect that patients who go on to receive third-line therapy are in better health/fitness.
Testing for cytogenic abnormalities was documented for 78% of our sample, which is higher than previously reported rates (ranging from 69 to 73%) [8, 12]. This could be reflective of the high proportion of younger patients within our sample. Patients for whom carfilzomib-including regimens were selected frequently had high-risk cytogenetics, and recent research has documented good efficacy of carfilzomib-including regimens in such groups [13, 14].
Approximately 30% of our sample had received a transplant before second-line therapy, comparable to rates earlier reported [8, 15–17]. Prior receipt of a transplant has been documented to be associated with greater likelihood of receiving D-containing or K-containing regimens in later lines [8]. Our study results did not replicate these findings; variability was shown in the proportions of patients receiving each later-line regimen who had received a transplant in earlier lines and no clear pattern emerged based on subsequent therapy type. However, Steinmetz et al. [8] included only patients who had received KRd, Kd, DRd, DVd, or R-including regimens in second and third lines. In contrast, our study allowed any type of approved regimen in second and third lines. Decisions concerning regimens for second- and third-line therapies did not appear to be driven by prior transplant receipt. Although we report a shorter median time to next treatment from second-line therapy for transplant-eligible patients (7 months) than for transplant-ineligible patients (21 months), this may be attributed to the small sample size of the transplant-eligible subgroup.
In second-line therapy, triplet therapy was frequently used and often included K and/or D, with DRd and KdD being the most frequently prescribed second-line regimens. The use of second-generation agents and monoclonal ABs in second-line settings in Germany and other European countries has previously been documented [8, 15, 18]. In third-line therapy, regimen choice was more diverse, but regimens were primarily IMiD-based, with R being the most frequent IMiD; the doublets Pd and Rd were most frequently used, as were the triplets DRd and EPd. Lehne et al. [17] similarly found that patients in Germany frequently received IMiD-including regimens from 2016 to 2020, with R-including regimens being the most frequent. Time to relapse among transplant-ineligible patients was longer for second-line therapy than first-line therapy, indicating the positive impact of anti-CD38-AB-containing regimens that were more commonly used in second-line than first-line, despite the higher number of high-risk patients in second-line. Although we observed that re-treatment with the anti-CD38-AB-containing regimen was uncommon, this is likely a reflection of the study design, because patients with a higher risk of progression are more likely to receive follow-up therapy. As a result, our sample is composed of many high-risk patients and likely does not reflect patients who received particularly effective first-line therapies. Treatment choices are complex due to the availability of novel therapeutic options, mostly applied as combination regimens [19]. Data from the large global prospective observational study, INSIGHT MM, similarly indicate that there is no global treatment standard [20, 21].
In our questionnaire, it was asked whether patients were eligible for transplant at the beginning of second- and third-line therapies. However, information about SCT received during these lines was not collected since the documentation of therapy ended with the initiation of second- and third-line therapies. Although this is rarely the case in Germany, there is published evidence that high-dose melphalan plus auto-SCT therapy may be an option in second-line therapy for patients who did not receive this therapy in first-line therapy [22].
Unlike in previous reports, we directly asked physicians to state their most important treatment goals and their primary reasons for selecting regimens. Regardless of treatment line, primary treatment goals were induction of deepest possible response and prolongation of OS and PFS, while recovery of QoL and symptomatic control were important for doublet second-line therapies, and for third-line regimens. The second most important treatment goals were recovery of QoL and symptomatic control independent of treatment line and doublet or triplet therapy. Physicians primarily selected regimens on the basis of efficacy, patient age and fitness, tolerability/toxicity considerations, comorbidities, and QoL. A hypothetical physician preference study conducted in the United States similarly reported that efficacy and prolongation of survival were key factors in treatment decision-making for RRMM [23, 24]. To expand on these findings, it would be valuable to conduct a prospective study looking at similar aspects that would allow examination of the decision-making process more precisely at the time of the actual decision. The findings from such a prospective study could be used to design future studies specifically tailored to the needs of decision-makers.
Our cross-sectional, retrospective study has the following limitations. Physicians and patients selected for study inclusion represent a convenience (i.e., non-random) sample. Therefore, study findings may have limited generalizability to the population of patients with MM in Germany and the physicians who treat them. All data captured were limited to data available in the medical records to which the physician had access. Unlike clinical trial settings with specific definitions of study outcomes and scheduled assessments described in the protocol, it is not possible in real-world retrospective studies to implement consistent monitoring nor application of homogenous evaluation criteria. Physicians were asked to report their reasons for prescribing regimens during 2021, and this information may be subject to recall bias, given that the data were collected during 2023. Restricting the eligible sample to patients who received a second- or third-line regimen during a single year may have led physicians to preferentially select patients with higher risk or earlier/more frequent progression [7]. Moreover, younger and higher-risk patients are treated in hospitals in Germany, while patients who are older and those with more comorbidities are commonly treated in office-based clinics, so the fact that our sample was mostly made up of physicians who were in a hospital setting means that older patients and those with more comorbidities might be underrepresented. Finally, the variability in regimen selection led to very few patients represented by each type of regimen, and thus a lot of between-patient variability within regimens (reflected by the large standard deviations) occurred, which impacts the ability to draw conclusions about specific regimens.
The results from our study support the notion that there is no standard of care for RRMM in later lines of treatment, and treatment choices appear to be made using a patient-centred approach. Patients have also reported that it is important for them to be involved in the decision-making process and to receive information on treatment effectiveness, future treatment options, and QoL after treatment [25, 26].
Conclusion
While physicians have many options for combination therapies from which to choose to meet individual patient goals, triplet therapies were frequently selected to treat RRMM in second-line and third-line in Germany to achieve the greatest efficacy as measured by depth of response and duration of survival. Many of the selected combinations have not been formally compared against each other in controlled settings. Providing individualised treatment for MM-patients is important, as one treatment does not fit all patients, and approved MM-treatment options allow physicians to personalise treatment according to their patient’s condition. In our study, we demonstrated that there is great variability in MM-therapy options that allow individual, patient-based therapy decisions to achieve MM-patient goals.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgments
Medical Writing, Editorial, and Other Assistance
Medical writing, editing, and design support was provided by John Forbes and Emily Gill of RTI-HS; funded by Amgen GmbH (Germany). Editorial support was also provided by Carine Thual of Amgen (Europe) GmbH.
Authorship
H. Tilman Steinmetz, Franziska Ertel, Beate Brinkmann, Katherine Houghton, and Carmen Flossmann contributed to the study conception and design and material preparation. Data collection and analysis were performed by Katherine Houghton and Tram Nham. The first draft of the manuscript was written by Katherine Houghton, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Participation
We thank all participants of the study.
Funding
This study as well as the Rapid Service Fee and Open Access Fee for publishing this article were funded by Amgen GmbH (Germany).
Data Availability
Qualified researchers may request data from Amgen clinical studies. Further details are available at Amgen’s website on Clinical Trial Data Sharing Requests.
Declarations
Conflict of Interest
Dr. H. Tilman Steinmetz has received research funding from Accord Healthcare, Amgen, Celgene, Novartis, Vifor; he has membership on an entity’s board of directors, speaker’s bureau, or its advisory committees with AbbVie, Accord Healthcare, Alexion, Amgen, Ariad, Bluebird Bio, BMS/Celgene, Boehringer, Gilead, Hexal/Sandoz, Incyte, IoMedico, Janssen-Cilag, Lilly, Miltenyi, Novartis, Oncopeptides, Otsuka, Pfizer, Pharmacosmos, Sanofi, Shire, Sobi, Stemline, TAD, Takeda, Vifor; and has received travel grants from Alexion, Amgen, Bayer, BMS/Celgene, Janssen-Cilag, Sanofi, Sobi, and Takeda. Katherine Houghton and Tram Nham are employees of RTI Health Solutions, which received funding from Amgen GmbH (Germany) to conduct this research study and to provide medical writing support. Beate Brinkmann, Dr. Franziska Ertel, and Dr. Carmen Flossmann are employees of Amgen GmbH (Germany) and hold Amgen stocks.
Ethics/Ethical Approval
This study was conducted retrospectively from data obtained for clinical purposes and complied with all relevant market research guidelines and legal obligations. No identifiable protected health information was extracted during the study, and the authors consulted with the institutional review board (IRB) of Nordrhein (Düsseldorf), who determined that the present study did not need ethical approval owing to the anonymisation of the data collected. An official waiver of ethical approval was granted from the IRB of Nordrhein (Düsseldorf) on 31 May 2023.
Footnotes
Prior presentation: Steinmetz T, Ertel F, Brinkmann B, Houghton K, Nham T, Flossmann C. Treatment goals and decision-making criteria for second- and third-line therapy for multiple myeloma in Germany. Poster presented at the European Hematology Association (EHA) 2024 Hybrid Congress; June 13, 2024. Madrid, Spain.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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