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CARVYKTI® (ciltacabtagene autoleucel)

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CARVYKTI - LocoMMotion (MMY4001) Study

Last Updated: 07/23/2025

SUMMARY

  • LocoMMotion was a prospective, noninterventional, multinational study evaluating the efficacy and safety of current, real-life, standard-of-care (SOC) antimyeloma treatments in patients with relapsed/refractory multiple myeloma (RRMM) who received ≥3 prior lines of therapy (LOTs).1-5
    • At a median follow-up of 26.4 months (95% confidence interval [CI], 25.0-28.1), the overall response rate (ORR) among the 248 enrolled patients was 31.9% (95% CI, 26.1-38.0).4
    • The median progression-free survival (PFS) was 4.6 months (95% CI, 3.9-5.6), and the median overall survival (OS) was 13.8 months (95% CI, 10.8-17.0).4
    • The median duration of treatment was 4.0 months (range, 0.1-33.6) and the median duration of response (DOR) was 7.4 months (95% CI, 4.9-11.1).4
    • An adverse event (AE) was reported in 86.7% of patients during the index LOT. The most commonly reported AEs were cytopenias.4
    • A total of 158 patients (63.7%) died during the study, predominantly due to progressive disease (PD).4
  • A final analysis of the LocoMMotion study was conducted that reported mature survival data, additional subgroup analyses, subsequent therapies and their outcomes, as well as long-term safety data from the LocoMMotion study.6
    • None of the patients achieved stringent complete response.
    • Prespecified subgroup analysis showed that ORR was minimally impacted by high-risk disease characteristics at baseline.
    • During the index LOT, an AE was reported in 86.7% of patients, with 63.7% of patients dying during the study, predominantly due to progressive PD.
  • Efficacy outcomes were evaluated in key subgroups of patients participating in the LocoMMotion study after a median follow-up of 16 months.7
    • The ORR ranged from 11.8% to 43.9% across all subgroups. The characteristics associated with worse efficacy outcomes included tripleclass refractory, penta-drug exposed, penta-drug refractory, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥1, poor renal function (creatinine clearance ≤60 mL/min), International Staging System (ISS) stage II-III, presence of extramedullary plasmacytomas, high lactate dehydrogenase (LDH; >245 U/L), bone marrow plasma cells ≥60%, and high-risk cytogenetics.
  • An analysis of health-related quality of life (HRQoL) was conducted in patients in the LocoMMotion study.8
    • In the overall population, the least square (LS) mean changes from baseline during SOC treatment showed minimal improvement in HRQoL, primarily worsening during subsequent treatment.
    • Patients who achieved very good partial response (≥VGPR) during SOC treatment had a greater improvement in patient-reported outcome (PRO) scores, including LS mean change for pain score.

CLINICAL DATA

LocoMMotion (MMY4001; clinicaltrials.gov identifier: NCT04035226) was a prospective, noninterventional, multinational study evaluating the efficacy and safety of current, real-life, SOC antimyeloma treatments in patients with RRMM who received ≥3 prior LOTs.1-5

Study Design/Methods

  • The study was conducted in the United States and 9 European countries (Germany, France, Spain, Italy, United Kingdom, Poland, Russia, the Netherlands, and Belgium).2
  • The study design is summarized in Figure: LocoMMotion Study Design.

LocoMMotion Study Design1-5

Abbreviations: CD, cluster of differentiation; CBR, clinical benefit rate; CR, complete response; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IMWG, International Myeloma Working Group; mAb, monoclonal antibody; MM, multiple myeloma; MR, minimal response; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PFS2, time to progression on the next line of subsequent antimyeloma therapy or death, whichever occurs first; PI, proteasome inhibitor; PR, partial response; PRO, patient-reported outcome; sCR, stringent complete response; SOC, standard of care; VGPR, very good partial response.
aProgressive disease/responses were assessed by response review committee. Responses with subsequent LOTs were subject to investigator assessment.
bCBR is defined as the percentage of patients with clinical benefit. CBR = ORR (sCR + CR + VGPR + PR) + MR.

Results

Patient Characteristics

  • Overall, 248 patients were included in the study, all of whom received a median of 4 prior LOTs (range, 2-13).3 The baseline patient characteristics are summarized in Table: Baseline Patient Demographics and Characteristics.
  • The index LOT included 91 unique treatment regimens. A total of 65.3% of patients (n=162) received a combination of ≥3 drugs and 2.4% of patients had a stem cell transplant (SCT).4 SOC regimens are summarized in Table: Antimyeloma SOC Treatments.

Baseline Patient Demographics and Characteristics2,3,9
Patient Characteristic
Total (N=248)
Median age, years (range)
68 (41-89)
Sex, male, n (%)
135 (54.4)
Geographic region, n (%)
   US
23 (9.3)
   Europe
225 (90.7)
Racea, n (%)
   White
182 (73.7)
   Black or African American
5 (2.0)
   Other
1 (0.4)
   Unknown/not reported
59 (23.9)
Baseline ECOG PSb, n (%)
   0
65 (26.2)
   1
179 (72.2)
   2
3 (1.2)
   3
1 (0.4)
Median years since initial MM diagnosis (range)
6.3 (0.3-22.8)
Median number of prior LOTs (range)
4 (2-13)
Prior LOTsc, n (%)
   2
16 (6.5)
   3
48 (19.4)
   4
62 (25.0)
   ≥5
122 (49.2)
ISS stage at enrollmentd, n (%)
   I
70 (32.3)
   II
69 (31.8)
   III
78 (35.9)
Presence of extramedullary plasmacytomasc, n (%)
   Yes
33 (13.3)
   No
215 (86.7)
Type of measurable diseasec, n (%)
   Serum only
123 (49.6)
   Serum and urine
19 (7.7)
   Urine only
22 (8.9)
   Serum free light chain
82 (33.1)
   Not evaluable
2 (0.8)
Previous stem cell transplant, n (%)
160 (64.5)
Creatinine clearancec, n (%)
   ≤60 mL/min
94 (40.0)
   >60 mL/min
141 (60.0)
Triple-class exposedc, n (%)
248 (100)
Refractory status, n (%)
   Any PI
197 (79.4)
   Any immunomodulatory drugs
233 (94.0)
   Any anti-CD38 mAb
229 (92.3)
   Triple-class refractorye
182 (73.4)
   Penta-drug refractoryf
43 (17.3)
   Refractory to last line of prior therapy, n (%)
230 (92.7)
Abbreviations: CD, cluster of differentiation; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; LOT, line of therapy; mAb, monoclonal antibody; MM, multiple myeloma; PI, proteasome inhibitor; US, United States.
aN=247.
bScreening ECOG PS scores were 0 or 1 only.
cBased on a median follow-up of 11 months.
dN=217.
ePI, immunomodulatory drug, and anti-CD38 mAB.
f2 PIs, 2 immunomodulatory drugs and anti-CD38 mAb.

Antimyeloma SOC Treatments3
SOC Treatments, n (%)
N=248
Autologous stem cell transplant
6 (2.4)
Glucocorticoids
222 (89.5)
PI
134 (54.0)
Immunomodulatory drugs
118 (47.6)
Alkylating agents
107 (43.1)
Anti-CD38 mAbs
24 (9.7)
Anthracyclines
18 (7.3)
Topoisomerase inhibitor
16 (6.5)
Other antineoplastic agents
15 (6.0)
HDAC inhibitors
12 (4.8)
Anti-SLAMF7 mAbs
9 (3.6)
BCMA-targeted ADC
7 (2.8)
BCL-2 inhibitor
6 (2.4)
Mitotic inhibitor
2 (0.8)
SINE
2 (0.8)
Abbreviations: ADC, antibody-drug conjugate; BCL-2, B-cell lymphoma 2; BCMA, B-cell maturation antigen; CD, cluster of differentiation; HDAC, histone deacetylase; mAb, monoclonal antibody; PI, proteasome inhibitor; SINE, selective inhibitor of nuclear export; SLAM, signaling lymphocytic activation molecule; SOC, standard of care.

Efficacy - Final Analysis

  • The median duration of follow-up was 26.4 months (95% CI, 25.0-28.1).4
Index SOC Treatment

Efficacy Outcomes of Patients on SOC Therapy (Final Analysis)4,6
Parameter
Total (N=248)
ORR, % (95% CI)
31.9 (26.1-38.0)
Median duration of treatment, months (range)
4.0 (0.1-33.6)
Median DOR, months (95% CI)
7.4 (4.9-11.1)
Best response rate, n (%)
   sCR
0
   CR
1 (0.4)
   VGPR
32 (12.9)
   PR
46 (18.5)
   Minimal response
14 (5.6)
   Stable disease
78 (31.5)
   PD
43 (17.3)
Median PFS, months (95% CI)
4.6 (3.9-5.6)
   12-month PFS rate, % (95% CI)
21 (15.3-27.3)
   24-month PFS rate, % (95% CI)
10.5 (6.1-16.3)
Median OS, months (95% CI)
13.8 (10.8-17.0)
   12-month OS rate, % (95% CI)
53.4 (46.7-59.6)
   24-month OS rate, % (95% CI)
33.7 (27.3-40.2)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; ORR; overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; SOC, standard of care; VGPR, very good partial response.
Subsequent LOTs
  • Overall, 152 patients (61.3%) received a subsequent LOT. A total of 78 patients had 1 subsequent LOT and 74 patients had ≥2 subsequent LOTs (1 LOT, 31%; 2 LOTs, 13%; 3 LOTs, 10%; >3 LOTs, 7%).4
  • The median progression-free survival on the subsequent LOT (PFS2) by investigator assessment was 10.8 months (95% CI, 8.4-13.0). Only PFS events that occurred after starting the subsequent LOT was considered, and patients who withdrew before subsequent LOT 1 were censored.4
  • A total of 79 different regimens were used in subsequent LOT 1. The most common subsequent LOT regimens are detailed in Table: Treatment Regimens Used in Index and Subsequent LOTs. The median duration of treatment was 2.8 months (range, <1-29.7).4
    • The usage of B cell maturation antigen (BCMA)-targeted therapy increased from 2.8% in index LOT to 24.2% in the subsequent LOT.

Treatment Regimens Used in Index and Subsequent LOTs4,6
LOT
No. of Regimens
No. of Patients
Most Common Regimens,a,b %
Index LOT
91
248
Kd (14.1), CPd (14.1), Pd (11.7)
Subsequent LOT 1
78
152
blmf (6.5), CPd (4.0)
Subsequent LOT 2
47
74
blmf (5.6), KCd (1.6), Kd (1.6)
Subsequent LOT 3
30
42
blmf (3.2), IPd (2), DKd (0.8)
Subsequent LOT 4+
34
17
blmf (1.2)
Abbreviations: blmf, belantamab mafodotin; CPd, cyclophosphamide, pomalidomide, and dexamethasone; DKd, DARZALEX, carfilzomib, and dexamethasone; IPd, isatuximab, pomalidomide, and dexamethasone; KCd, carfilzomib, cyclophosphamide, and dexamethasone; Kd, carfilzomib and dexamethasone; Pd, pomalidomide and dexamethasone.
aPatients can be counted in more than one regimen.
bPercentage calculated out of N=248; for subsequent LOT, the percentage does not account for patients who died or were lost to follow-up.

Efficacy - Primary and Updated Analyses


Efficacy Outcomes of Patients on SOC Therapy (Primary and Updated Analyses)2,3
Parameter
Total (N=248)
11.0 Month Follow-up
16.1-Month Follow-up
ORR, % (95% CI)
29.8 (24.2-36.0)
31.5 (25.7-37.6)
   Triple class refractory at baselinea
25.1 (19.0-32.1)
-
   Not triple class refractory at baselineb
43.1 (30.8-56.0)
-
Best response rate, %
   sCR
0
0
   CR
0.4
0.4
   VGPR
12.1
12.9
   PR
17.3
18.1
   Minimal response
5.2
-
   Stable disease
31.0
-
   PD
18.5
-
   NEc
15.3
-
Median PFS, months (95% CI)
4.6 (3.9-5.6)
4.6 (3.9-5.6)
   Patients not achieving VGPR
3.9 (3.4-4.6)
3.9 (3.4-4.6)
   Patients achieving VGPR or better
NR (8.54-NE)
15.2 (13.3-NE)
   Triple class refractory at baseline
3.9 (3.4-4.6)
-
   Not triple class refractory at baseline
8.2 (5.7-12.0)
-
12-month PFS rate, % (95% CI)
19.9 (13.6-27.0)
-
Median PFS from the initiation of SOC through subsequent LOTs (PFS2), months (95% CI)
-
9.9 (7.6-12.0)
Median OS, months (95% CI)
12.4 (10.28-NE)
13.8 (10.8-18.5)
   Patients not achieving VGPR
10.9 (8.4-14.2)
10.9 (8.4-14.2)
   Patients achieving VGPR or better
NE (NE-NE)
NE (17.9-NE)
   Triple class refractory at baseline
11.1 (8.8-14.2)
-
   Not triple class refractory at baseline
NE (12.4-NE)
-
12-month OS rate, % (95% CI)
51.8 (44.1-58.8)
-
Median DOR, months (95% CI)
7.4 (4.7-12.5)
7.7 (5.1-13.1)
   Patients not achieving VGPR
4.5 (3.5-7.3)
-
   Patients achieving VGPR or better
NE (7.7-NE)
-
   Triple class refractory at baseline
4.5 (3.7-NE)
-
   Not triple class refractory at baseline
9.1 (7.3-NE)
-
Median time to first response, months (range)
1.9 (0.7-9.5)
-
Median time to best response, months (range)
2.4 (0.7-12.2)
-
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NE, not estimable; NR, not reached; ORR; overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; SOC, standard of care; VGPR, very good partial response.
aN=183.
bN=65.
cFourteen patients were NE due to death within 2 months after initiating SOC therapy; 12 patients were NE due to discontinuation or switching of SOC therapy.

Safety - Final Analysis

  • During the index LOT, an AE was reported in 86.7% of patients. See details in Table: TEAEs During the Index LOT and Summary of TEAEs and SPM.
    • SPMs were reported in 13 patients (5.2%), five were reported during index LOT, while eight were reported after index LOT.6 
  • During the study, 158 patients (63.7%) died, with the majority of deaths (67.7%) attributed to PD (regardless of the stage of treatment [during or after index LOT or after starting subsequent LOTs]), 15.8% due to AEs, and 16.5% from other causes.4,6
    • Sixty deaths occurred during or after the index LOT but before subsequent LOTs, while 98 deaths occurred after the start of subsequent LOTs.
    • During the index LOT, 21 patients (8.5%) died from TEAEs, most commonly infections (13 patients, 5.2%), and one patient had a grade 5 TEAE that did not resolve before dying from PD.

TEAEs During the Index LOT6 
TEAE, n (%)
N=248
Any TEAE
215 (86.7)
Any serious TEAE
91 (36.7)
Maximum severity of TEAE
   Grade 1
17 (6.9)
   Grade 2
46 (18.5)
   Grade 3
84 (33.9)
   Grade 4
46 (18.5)
   Grade 5
22 (8.9)
TEAE with death as the outcome
21 (8.5)a
Abbreviations: LOT, line of therapy, PD, progressive disease, TEAE, treatment-emergent adverse event.
a1 patient with unresolved grade 5 TEAE died from PD.

Summary of TEAEs and SPM6 
TEAE
Any Grade
Grade 3/4
Hematologic TEAEs, %
   Thrombocytopenia
26.2
19.4
   Anemia
25.8
10.9
   Neutropenia
20.2
17.3
Non-hematologic TEAEs, %
   General disorders and
   administration site
   conditions
40.7
-
   Gastrointestinal disorders
33.5
-
   Infections and infestations
33.1
-
SPMs, n
   Squamous cell carcinoma
4
-
   Basal cell carcinoma
2
-
   Secondary acute myeloid
   leukemia
2
-
   Cancer of the
   lung/bronchus
2
-
   High-grade suspected
   cholangiocellular
   carcinoma
1
-
   Plasma cell leukemia
1
-
   Multiple destructive FDG-
   positive lesions
   throughout the skeleton
   and skull
1
-
Fatal SPMs
1
-
Abbreviations: FDG, flurodeoxyglucose; SPM, second primary malignancy; TEAE, treatment-emergent adverse event.

Safety - Primary and Updated Analyses

  • Overall, at a median follow-up of 26.4 months, an AE was reported in 86.7% of patients during the index LOT. The most common AEs reported were cytopenias.4
    • At a median follow-up of 16.1 months, treatment-emergent adverse events (TEAEs) had been reported in 85.9% of patients (n=213), of whom 56.5% (n=140) reported grade 3/4 TEAEs. The most common grade 3/4 TEAEs were hematologic; thrombocytopenia (18.5%), neutropenia (16.1%), and anemia (10.1%).3
    • Non-hematologic TEAEs at a median follow-up of 11.01 months are summarized in
      Table: Non-hematologic TEAEs at a Median Follow-Up of 11.01 Months.
  • A second primary malignancy was reported in 13 patients (5.2%; during index LOT, n=5; after index LOT, n=8).4
  • Throughout the entire study period, 158 patients (63.7%) died, predominantly due to PD, regardless of the stage of treatment (during or after index LOT or after starting subsequent LOTs).4

Non-hematologic TEAEs at a Median Follow-Up of 11.01 Months2
TEAE
Total (N=248)
Any Grade, n (%)a
Grade 3/4, n (%)a
Non-hematologic TEAEsb
   Infections and infestations
71 (28.6)
16 (6.5)
   Nervous system disorders
49 (19.8)
8 (3.2)
General disorders and administration site conditions
   Pyrexia
31 (12.5)
6 (2.4)
   Fatigue
30 (12.1)
2 (0.8)
   Asthenia
23 (9.3)
2 (1.2)
   Peripheral edema
19 (7.7)
1 (0.4)
Gastrointestinal disorders
   Diarrhea
38 (15.3)
2 (0.8)
   Nausea
23 (9.3)
3 (1.2)
   Constipation
14 (5.6)
0
   Vomiting
14 (5.6)
2 (0.8)
   Metabolism and nutrition disorders
31 (12.5)
9 (3.6)
Musculoskeletal and connective tissue disorders
   Back pain
20 (8.1)
4 (1.6)
   Arthralgia
15 (6.0)
3 (1.2)
Respiratory, thoracic, and mediastinal disorders
   Dyspnea
28 (11.3)
6 (2.4)
   Investigations
25 (10.1)
6 (2.4)
   Psychiatric disorders
22 (8.9)
3 (1.2)
   Renal and urinary disorders
22 (8.9)
13 (5.2)
   Injury, poisoning, and procedural complications
21 (8.5)
6 (2.4)
   Skin and subcutaneous tissue disorders
20 (8.1)
1 (0.4)
   Cardiac disorders
18 (7.3)
9 (3.6)
   Vascular disorders
18 (7.3)
7 (2.8)
Abbreviations: TEAE, treatment-emergent adverse event.
aPercentages are calculated with the all-treated analysis set as denominator.
bReported in ≥5% of patients.

LocoMMotion Subgroup Analysis

Expanded Subgroup Outcomes Based on Final Analysis

Mateos et al (2024)6 reported mature survival data, additional subgroup analyses, subsequent therapies and their outcomes, as well as long-term safety data from the final analysis of the LocoMMotion study that explored the use of real-world clinical practice (RWCP) therapies in managing triple-class exposed patients with RRMM.

Results

Efficacy


Antimyeloma RWCP Treatments - Index and Subsequent LOTs6 
Treatment, n (%)a
Index LOT (N=248)
1st Subsequent LOT (n=152)
2nd Subsequent LOT (n=74)
3rd Subsequent LOT (n=42)
≥4th Subsequent LOT (n=17)
Glucocorticoids
227 (91.5)
107 (70.4)
47 (63.5)
23 (54.8)
9 (52.9)
PI
135 (54.4)
53 (34.9)
24 (32.4)
9 (21.4)
8 (47.1)
   Carfilzomib
63 (25.4)
22 (14.5)
11 (14.9)
3 (7.1)
3 (17.6)
   Bortezomib
50 (20.2)
24 (15.8)
10 (13.5)
5 (11.9)
6 (35.3)
   Ixazomib
22 (8.9)
7 (4.6)
3 (4.1)
1 (2.4)
1 (5.9)
IMiD
121 (48.8)
51 (33.6)
17 (23)
10 (23.8)
7 (41.2)
   Pomalidomide
74 (29.8)
30 (19.7)
7 (9.5)
6 (14.3)
4 (23.5)
   Lenalidomide
36 (14.5)
9 (5.9)
5 (6.8)
3 (7.1)
5 (29.4)
   Thalidomide
11 (4.4)
11 (7.2)
5 (6.8)
1 (2.4)
1 (5.9)
   Iberdomide
0 (0)
1 (0.7)
0 (0)
0 (0)
0 (0)
Alkylating agents
108 (43.5)
68 (44.7)
29 (39.2)
13 (31)
5 (29.4)
   Cyclophosphamide
80 (32.3)
43 (28.3)
17 (23)
7 (16.7)
4 (23.5)
   Bendamustine
16 (6.5)
14 (9.2)
6 (8.1)
2 (4.8)
0 (0)
   Melphalan
14 (5.6)
13 (8.6)
6 (8.1)
4 (9.5)
0 (0)
   Carmustine
1 (0.4)
1 (0.7)
1 (1.4)
1 (2.4)
0 (0)
   Other
1 (0.4)
0 (0)
0 (0)
1 (2.4)
0 (0)
   Melflufen
0 (0)
0 (0)
1 (1.4)
0 (0)
1 (5.9)
Anti-CD38 mAb
24 (9.7)
16 (10.5)
5 (6.8)
11 (26.2)
7 (41.2)
   Daratumumab
23 (9.3)
13 (8.6)
4 (5.4)
5 (11.9)
6 (35.3)
   Isatuximab
1 (0.4)
3 (2)
1 (1.4)
6 (14.3)
2 (11.8)
BCMA-targeted therapies
7 (2.8)
24 (15.8)
21 (28.4)
10 (23.8)
7 (41.2)
   CAR-T
0 (0)
0 (0)
2 (2.7)
0 (0)
1 (5.9)
   Bispecific antibody
0 (0)
5 (3.3)
2 (2.7)
0 (0)
4 (23.5)
   Antibody-drug
   conjugate
7 (2.8)
19 (12.5)
17 (23)
10 (23.8)
3 (17.6)
Anthracyclines
21 (8.5)
8 (5.3)
7 (9.5)
4 (9.5)
2 (11.8)
Topoisomerase inhibitor
17 (6.9)
6 (3.9)
3 (4.1)
1 (2.4)
0 (0)
Histone deacetylase inhibitor
12 (4.8)
6 (3.9)
0 (0)
0 (0)
0 (0)
Anti-SLAMF7 mAb
9 (3.6)
7 (4.6)
0 (0)
1 (2.4)
2 (11.8)
BCL-2 inhibitor
6 (2.4)
3 (2)
2 (2.7)
2 (4.8)
1 (5.9)
Selective inhibitor of nuclear export
2 (0.8)
11 (7.2)
3 (4.1)
3 (7.1)
4 (23.5)
Other
19 (7.67)
9 (5.9)
7 (9.5)
4 (9.5)
(23.5)
Abbreviations: BCL, B-cell lymphoma; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor;
CD, cluster of differentiation; IMiD, immunomodulatory drug; LOT, line of therapy; mAb, monoclonal antibody;
PI, proteasome inhibitor; RWCP, real-world clinical practice; SLAM, signalling lymphocytic activation molecule.
aPatients can be counted in >1 drug group.

Subgroup analysis of ORR6 
Variable
N
ORR, n (%)
95% CI
Age, years
<65
88
30 (34.1)
24.3-45.0
≥65
160
49 (30.6)
23.6-38.4
Creatinine clearance/GFR, mL/min
≥60
87
26 (29.9)
20.5-40.6
>60
130
45 (34.6)
26.5-43.5
Baseline ECOS PS
0
65
21 (32.3)
21.2-45.1
≥1
183
58 (31.9)
25.2-39.2
No. of LOTs
≤3
64
24 (37.5)
25.7-50.5
≥4
184
55 (29.9)
23.4-37.1
ISS stage at study entry
1
69
23 (33.3)
22.4-45.7
2
69
21 (30.4)
19.9-40.9
3
78
23 (29.5)
19.7-40.9
Triple-class refractorya
Yes
182
49 (26.9)
20.6-34.0
No
66
30 (45.5)
33.1-58.2
Penta-drug refractoryb
Yes
43
10 (23.3)
11.8-38.6
No
205
69 (33.7)
27.2-40.6
Penta-drug exposedb
Yes
112
32 (28.6)
20.4-37.9
No
136
47 (34.6)
26.6-43.2
Extramedullary plasmacytoma
Yes
24
7 (29.2)
12.6-51.1
No
224
72 (32.1)
26.1-38.7
LDH, U/L
≤245
119
41 (34.5)
26.0-43.7
>245
81
22 (27.2)
17.9-26.2
Platelets (109/L)
<75
61
9 (14.8)
7.0-26.2
≥75
181
68 (37.6)
30.5-45.1
Abbreviations: CD, cluster of differentiation; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group, GFR, glomerular filtration rate, IMiD, immunomodulatory drug; ISS, International Staging System, LDH, lactate dehydrogenase, LOT, line of therapy; ORR, overall response rate; PI, proteasome inhibitor; PS, performance status.
aTriple-class exposed/refractory is defined as exposed/refractory to a PI, an IMiD, and an anti-CD38 antibody. bPenta-drug exposed/refractory is defined as exposed/refractory to at least 2 PIs, 2 IMiDs, and 1 anti-CD38 antibody (includes triple-class exposed/refractory).

Efficacy Outcomes Stratified by Patient and Disease Characteristics

An analysis of efficacy outcomes stratified by treatment history, patient characteristics and disease characteristics was conducted in 248 patients participating in the LocoMMotion study at a median follow-up of 16 months.7

Results

Patient Characteristics

  • Overall, 248 patients were included. The duration of follow-up was 16 months, spanning a median of 4 cycles (range, 1-25) of SOC therapy.7

Efficacy

  • The ORR ranged from 11.8% to 43.9% across all subgroups.7
  • The characteristics associated with worse efficacy outcomes included triple class refractory, penta-drug exposed, penta-drug refractory, ECOG PS ≥1, poor renal function (creatinine clearance ≤60 mL/min), ISS stage II-III, presence of extramedullary plasmacytomas, high LDH (>245 U/L), bone marrow plasma cells ≥60%, and high-risk cytogenetics.7
  • Efficacy outcomes stratified by treatment history, patient characteristics, and disease characteristics are summarized in Table: Efficacy Outcomes by Patient Treatment History, Table: Efficacy Outcomes by Patient Characteristics, and Table: Efficacy Outcomes by Disease Characteristics, respectively.7

Efficacy Outcomes by Patients Treatment History7
Treatment History
Na
Median OS, Months
(95% CI)
Median PFS,
Months
(95% CI)
ORR, %
(95% CI)
Median DORb,
Months
(95% CI)
Overall
248
13.8 (10.8-18.5)
4.6 (3.9-5.6)
31.5 (25.7-37.6)
7.7 (5.1-13.1)
Number of LOTs
   ≤3
65
11.1 (7.4-15.1)
4.3 (3.1-6.0)
36.9 (25.3-49.8)
4.9 (3.4-NE)
   ≥4
183
15.9 (10.9-20.2)
4.9 (4.0-5.7)
29.5 (23.0-36.7)
9.0 (5.6-NE)
Triple-class refractory
   Yes
182
11.1 (9.0-15.9)
4.1 (3.4-4.6)
26.9 (20.6-34.0)
5.1 (4.0-9.0)
   No
66
NE (13.0-NE)
8.2 (5.7-12.9)
43.9 (31.7-56.7)
13.1 (7.7-NE)
Penta-drug exposed
   Yes
112
11.6 (8.2-17.9)
3.9 (3.0-5.1)
27.7 (19.6-36.9)
4.9 (3.7-NE)
   No
136
15.1 (11.1-NE)
5.6 (4.3-7.2)
34.6 (26.6-43.2)
11.1 (5.6-NE)
Penta-drug refractory
   Yes
43
8.2 (5.7-13.0)
3.4 (2.1-4.5)
23.3 (11.8-38.6)
4.0 (1.2-NE)
   No
205
15.5 (12.0-NE)
5.4 (4.2-6.0)
33.2 (26.8-40.1)
9.0 (5.1-17.8)
Abbreviations: CI, confidence interval; DOR, duration of response; LOT, line of therapy; NE, not estimable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
aN values correspond to ORR data.
bIn responders (partial response or better).

Efficacy Outcomes by Patient Characteristics7
Patient Characteristics
Na
Median OS, Months
(95% CI)
Median PFS,
Months
(95% CI)
ORR, %
(95% CI)
Median DORb,
Months
(95% CI)
Overall
248
13.8 (10.8-18.5)
4.6 (3.9-5.6)
31.5 (25.7-37.6)
7.7 (5.1-13.1)
Age, years
   <65
88
13.3 (8.9-NE)
4.4 (3.3-6.0)
34.1 (24.3-45.0)
11.1 (3.5-NE)
   ≥65
160
14.2 (10.3-18.5)
4.9 (3.7-5.7)
30.0 (23.0-37.7)
7.4 (5.0-13.1)
Baseline ECOG PS
   0
65
NE (18.5-NE)
5.7 (3.7-6.7)
30.8 (19.9-43.4)
8.1 (4.5-NE)
   ≥1
183
11.1 (7.6-13.8)
4.4 (3.6-5.6)
31.7 (25.0-39.0)
7.7 (4.9-17.8)
Baseline renal function (creatinine clearance), mL/min
   ≤60
92
11.1 (7.6-NE)
4.4 (3.5-5.7)
31.5 (22.2-42.0)
5.6 (4.5-9.0)
   >60
139
16.0 (11.8-NE)
5.1 (3.7-6.0)
33.1 (25.4-41.6)
13.1 (5.1-NE)
Abbreviations: CI, confidence interval; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; NE, not estimable; ORR, overall response rate; OS, overall survival; PFS, progressionfree survival.
aN values correspond to ORR data.
bIn responders (partial response or better).

Efficacy Outcomes by Disease Characteristics7
Disease Characteristics
Na
Median OS, Months
(95% CI)
Median PFS,
Months
(95% CI)
ORR, %
(95% CI)
Median DORb,
Months
(95% CI)
Overall
248
13.8 (10.8-18.5)
4.6 (3.9-5.6)
31.5 (25.7-37.6)
7.7 (5.1-13.1)
Baseline ISSc
   I
46
NE (20.2-NE)
6.0 (4.9-9.4)
37.0 (23.2-52.5)
NE (4.7-NE)
   II
38
8.4 (5.3-10.9)
3.9 (1.9-5.7)
21.1 (9.6-37.3)
5.1 (1.2-NE)
   III
40
16.4 (5.4-NE)
5.1 (3.5-6.4)
35.0 (20.6-51.7)
9.5 (2.6-NE)
Presence of extramedullary plasmacytomas
   Yes
26
6.3 (4.9-8.2)
2.3 (1.4-3.5)
23.1 (9.0-43.6)
11.1 (3.5-NE)
   No
222
15.5 (12.0-20.2)
5.1 (4.3-6.0)
32.4 (26.3-39.0)
7.7 (4.9-13.1)
LDH, U/L
   ≤245
114
19.4 (13.3-NE)
5.6 (4.6-6.3)
36.0 (27.2-45.5)
5.6 (4.5-NE)
   >245
79
8.1 (5.5-12.0)
3.4 (2.3-4.4)
26.6 (17.3-37.7)
9.5 (3.0-NE)
Bone marrow plasma cells, %
   ≤30
48
18.5 (12.4-NE)
4.9 (3.6-6.4)
29.2 (17.0-44.1)
NE (3.7-NE)
   >30 to <60
11
10.9 (4.1-NE)
5.4 (0.8-6.3)
27.3 (6.0-61.0)
4.5 (4.5-NE)
   ≥60
17
7.6 (2.6-11.8)
4.4 (1.0-8.5)
11.8 (1.5-36.4)
NE (5.0-NE)
Cytogenetic riskd
   High
11
6.2 (1.9-9.0)
4.9 (1.0-6.4)
18.2 (2.3-51.8)
4.3 (4.0-NE)
   Standard
29
18.5 (9.2-NE)
5.6 (2.0-9.9)
31.0 (15.3-50.8)
NE (4.7-NE)
Abbreviations: CI, confidence interval; del, deletion; DOR, duration of response; ISS, International Staging System; LDH, lactate dehydrogenase; NE, not estimable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; t, translocation.
aN values correspond to ORR data.
bIn responders (partial response or better).
cISS staging is calculated at study entry based on laboratory parameters for albumin and β2-microglobulin.
dMutations of t(4;14), t(14;16), or del17p13 were considered high-risk; cytogenetic assessments were performed at local laboratory.

Health-Related Quality of Life in patients in the locommotion study

An analysis of HRQoL was conducted in 248 patients in the LocoMMotion study.8

Study Design/Methods

  • HRQoL was assessed using the following PRO questionnaires8:
    • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item (EORTC QLQ-C30)
    • Four single items (ie, feeling restless or agitated, thinking about illness, worried about dying, worried about future health) from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire myeloma module (EORTC QLQ-C30 MY20).
    • EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L).
  • HRQoL was assessed at the following timepoints8:
    • Baseline (defined as the closest value to day 1 of SOC treatment; screening visit or cycle 1 day 1 visit)
    • Day 1 of each treatment cycle
    • End of treatment visit
    • During follow-up (every 4 weeks)

Results

  • Mean questionnaire response rate was approximately 78% during SOC treatment and approximately 71% during follow-up.8
  • In the overall population, the LS mean changes from baseline during SOC treatment showed minimal improvement in HRQoL, primarily worsening during subsequent treatment (see Table: LS Mean Changes in Scores From Baseline During SOC and Subsequent LOTs).8
  • Patients who achieved ≥VGPR during SOC treatment had greater improvement in PRO scores, including LS mean change for pain score (see Table: LS Mean Changes in Scores from Baseline by Response).8
  • A meaningful improvement in PRO scores (defined by a literature-based minimally important difference of 10 points in mean score) was not achieved in most patients, especially for pain symptoms.8

LS Mean Changes in Scores From Baseline During SOC and Subsequent LOTs8
Scale
LS mean change from baseline (95% CI)a
During SOC treatment (n=173)
During subsequent treatment (n=99)
EORTC QLQ-C30
   Physical functioningb
0.7 (-2.0, 3.4)
-11.2 (-15.5, -6.8)
   Global health statusb
2.9 (0.0, 5.9)d
-4.6 (-8.3, -0.9)e
   Pain scorec
-2.4 (-6.3, 1.5)
1.0 (-3.5, 5.4)
   Fatigue symptomsc
-2.4 (-5.5, 0.7)
6.5 (2.5, 10.4)
EORTC QLQ-MY20
   Restless or agitatedc
-5.1 (-8.8, -1.4)d
3.5 (-1.1, 8.1)e
   Thinking about illnessb
9.0 (4.9, 13.0)f
3.7 (-1.3, 8.8)e
   Worried about dyingb
4.8 (1.1, 8.4)d
-4.2 (-10.1, 1.8)e
   Worried about healthb
10.3 (6.5, 14.2)f
0.9 (-3.7, 5.6)
EQ-5D-5L
   Visual analog scaleb
2.2 (-0.1, 4.6)f
-4.0 (-7.5, -0.5)g
   Utility scoreb
0.00 (-0.03, 0.02)h
-0.04 (-0.07, 0.01)i
Abbreviations: EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item; EORTC QLQ-C30 MY20, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire myeloma module; EQ-5D-5L, EuroQol Five Dimension Five Level Questionnaire; LOT, line of therapy; LS, least square; SOC, standard of care.
aBolded scores indicate worsening.
bHigher score indicates better outcome.
cHigher score indicates worse outcome.
dn=171.
en=98.
fn=172.
gn=97.
hn=170.
in=95.

LS Mean Changes in Scores from Baseline by Responsea,8
Scale
LS mean change from baseline (95% CI)a
≥VGPR (n=25)
PR (n=42)
NR (n=71)
PD (n=26)
EORTC QLQ-C30
   Physical functioningb
1.9
(-3.0, 6.7)
3.9
(-0.4, 8.3)
-2.8
(-8.3, 2.6)
-8.9
(-17.6, -0.3)
   Global health statusb
6.4
(1.2, 11.7)
5.6
(0.5, 10.7)d
-3.5
(-8.6, 1.7)e
-7.2
(-14.8, 0.4)
   Painc
-14.1
(-21.5, -6.7)
-2.2
(-8.7, 4.4)
2.3
(-3.6, 8.2)
8.5
(-3.0, 20.1)
   Fatiguec
-5.8 (-11.2, -0.5)
-0.7 (-5.8, 4.5)
-2.6 (-7.7, 2.5)
-1.8 (-9.2, 5.6)
EORTC QLQ-MY20
   Restless or agitatedc
2.2 (-3.5, 8.0)
-5.4 (-11.8, 1.1)
-5.0 (-10.7, 0.6)f
-6.6 (-19.8, 6.7)
   Thinking about illnessb
10.1 (4.0, 16.2)
11.5 (4.8, 18.3)
7.1 (0.5, 13.6)e
-0.5 (-12.9, 11.9)
   Worried about dyingb
2.1 (-3.6, 7.8)
10.5 (4.1, 16.9)
-0.3 (-6.3, 5.7)f
0.1 (-7.2, 7.5)
   Worried about healthb
8.0 (0.8, 15.2)
13.3 (7.2, 19.4)
4.9 (-1.0, 10.9)e
-0.1 (-12.2, 11.9)
EQ-5D-5L
Visual analog scaleb
5.6 (1.2, 10.0)g
5.7 (1.9, 9.5)
-1.3 (-5.1, 2.5)
-9.9 (-16.7, -3.0)
Utility scoreb
0.03
(-0.02, 0.08)g
0.01
(-0.02, 0.04)
-0.01
(-0.05, 0.02)f
-0.09
(-0.14, -0.03)
Abbreviations: EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item; EORTC QLQ-C30 MY20, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire myeloma module; EQ-5D-5L, EuroQol Five Dimension Five Level Questionnaire; LS, least square; NR, nonresponder; PD, progressive disease; PR, partial response; VGPR, very good partial response.
aBolded scores indicate worsening.
bHigher score indicates better outcome.
cHigher score indicates worse outcome.
dn=41.
en=70.
fn=69.
fn=24.
Note: Non-evaluable patients were excluded from analysis.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 26 June 2025.

 

References

Show
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2 Mateos MV, Weisel K, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia. 2022;36(5):1371-1376.  
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5 Mateos MV, Weisel K, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma receiving ≥3 prior lines of therapy. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021; Virtual Meeting.  
6 Mateos MV, Weisel K, Stefano VD, et al. LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis). Leukemia. 2024;38 (12):2554-2560.  
7 Einsele H, Moreau P, De Stefano V, et al. Subgroup analyses in patients with relapsed/refractory multiple myeloma receiving real-life current standard of care in the LocoMMotion study. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.  
8 Delforge M, Moreau P, Einsele H, et al. Health-related quality of life in patients with relapsed/refractory multiple myeloma receiving real-life current standard of care in the LocoMMotion study. Oral Presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL & Virtual.  
9 Moreau P, Weisel K, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational  study of real-life current standards of care in patients with relapsed/refractory multiple myeloma who  received ≥3 prior lines of therapy. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA/Virtual Meeting.