Teclistamab in Elderly Patients With Relapsed/Refractory Multiple Myeloma: A Subgroup Analysis of the French RetrosTECtive Cohort

ABSTRACT

Introduction

Real‐world data on teclistamab in relapsed or refractory multiple myeloma (R/R MM), particularly in elderly patients, remain limited.

Methods

We analysed efficacy and safety outcomes in patients ≥ 75 years from the French RetrosTECtive cohort. Among 303 patients, 90 were aged ≥ 75 years and compared with 213 younger patients.

Results

Elderly patients had fewer high‐risk cytogenetic abnormalities and a longer disease history. Remarkably, teclistamab appeared more effective in this population, with 74% achieving at least a very good partial response, compared with 62% of younger patients. Median progression‐free survival was 15.1 months in the elderly cohort versus 12.4 months in younger patients.

Conclusion

This improved efficacy did not come at the cost of increased toxicity: adverse event rates were comparable, although older patients more frequently received prophylactic measures. These findings support teclistamab as a safe and effective therapeutic option for geriatric patients with R/R MM.

Trial Registration

The authors have confirmed clinical trial registration is not needed for this submission.

1. Introduction

Teclistamab, the first bispecific antibody targeting both B‐cell maturation antigen (BCMA) and CD3 (BCMAxCD3), was approved for relapsed or refractory multiple myeloma (R/R‐MM) based on the MajesTEC‐1 trial [1]. In that study, teclistamab yielded a median progression‐free survival (PFS) of 11.3 months and an overall response rate (ORR) of 63% after a median follow‐up of 14 months, with an approximately 40% of patients achieving complete response (CR). These results established teclistamab as a treatment offering durable and deep responses with manageable toxicity.

However, the MajesTEC‐1 trial had restrictive eligibility criteria, and only 14% of participants were aged ≥ 75 years. This contrasts with real‐world demographics: in France, the median age at myeloma diagnosis is 70 years for men and 74 years for women, with around one‐third of patients ≥ 75 years and 20%–25% ≥ 80 years at diagnosis [2]. Data on this older and often frailer population, who account for a substantial proportion of patients encountered in clinical practice, remain scarce.

The RetrosTECtive study [3] included 303 patients with R/R‐MM who had received more than or equal to three prior lines of therapy and were treated with teclistamab across 30 French centres between October 2022 and September 2023. Approximately one‐third of enrolled patients were aged ≥ 75 years, underscoring the importance of evaluating outcomes in this subgroup. With an ageing population and higher comorbidity burden, real‐world studies are essential to complement clinical trials and better reflect clinical practice. Aside from a recent US series [4], evidence on teclistamab in the elderly remains limited.

The objective of this study was to compare patient characteristics, cytogenetic risk, efficacy and safety of teclistamab in elderly (≥ 75 years) versus younger (< 75 years) patients.

2. Materials and Methods

Patients from the RetrosTECtive cohort were stratified by age using the ≥ 75 years cut‐off applied in MajesTEC‐1. After patient consent, data were collected by treating physicians across 26 French centres and entered into a dedicated web‐based database. Demographics, comorbidities, prior therapies and cytogenetic risk profiles were analysed.

2.1. Treatment

Teclistamab was administered subcutaneously every week at 1.5 mg/kg following two step‐up doses of 0.06 and 0.3 mg/kg including premedication as recommended by the European Medicines Agency. All patients were treated in university or community hospitals, no patients were treated outside of hospital.

2.2. Frailty

The evaluation of patients' frailty was also considered in relation to efficacy and toxicity. Frailty was defined as follows: patients aged over 75 with comorbidities, and patients younger than 75 with an ECOG score of 2 or more were considered frail, others were considered fit.

2.3. Patient's Evaluation and AE's Grading

Performance Status was assessed using the Eastern Cooperative Oncology Group (ECOG) scale. High‐risk cytogenetics were defined as the presence of TP53 mutation, del(17p), t(4;14), t(14;16) and/or gain (1q).

The International Myeloma Working Group (IMWG) was used to evaluate the best response to treatment in patients. Adverse effects, such as immune effector cell‐associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), were evaluated at each hospital using the recommended, published grading scales [5]. Only cases of CRS and ICANS of Grade 2 or above were collected, as these imply the use of dedicated therapy.

2.4. Statistical Analysis

Descriptive statistics summarised baseline characteristics. Kaplan–Meier estimates were used for PFS and OS, with 95% confidence interval (CI), the Log‐rank test was used for group comparison. Comparisons between groups used the chi‐square test or Fisher's exact test, as appropriate. A two‐sided p‐value < 0.05 was considered statistically significant.

PFS was defined as the time from teclistamab initiation to disease progression or death, whichever occurred first. Overall survival (OS) was defined as the time from teclistamab initiation to death from any cause.

3. Results

3.1. Patient Characteristics

Ninety patients aged 75 years or older (≥ 75 group), were identified from the RetrosTECtive cohort and compared with 213 patients (< 75 group). The median age of the elderly cohort was 78 years (range, 75–88), including 38 patients (13%) aged ≥ 80 years, compared with a median age of 66 years, (range, 37–74) in the younger cohort (Table 1). Women were more frequent among older patients (61% vs. 45.5%, p = 0.0134). Comorbidities were more common in the elderly group (mean 1, 26 vs. 1; p = 0.005).

TABLE 1.

Patients, disease and treatment characteristics.

Characteristic	All patients (N = 303)	< 75 years old (N = 213)	≥ 75 years old (N = 90)
Patient age, years, median (min‐max) [IQR]	70 (37–88) [63–75]	66 (37–74) [58.25–71]	78 (75–88) [76–82]
Gender
Male	49.8%	54.5%	39%
Female	50.2%	45.5%	61%
ECOG‐PS
0	38 (15%)	29 (16%)	9 (13%)
1	119 (47.6%)	85 (47%)	34 (49%)
≥ 2	92 (37%)	65 (36%)	27 (39%)
Missing	53	34	20
Mutated TP53
No	54 (67%)	40 (63%)	14 (82%)
Yes	27 (33%)	24 (37%)	3 (18%)
Missing	222	149	73
del(17p)
No	137 (81%)	107 (79%)	30 (86%)
Yes	33 (19%)	28 (21%)	5 (14%)
Missing	133	78	55
t(4;14)
No	151 (85%)	116 (83%)	35 (92%)
Yes	27 (15%)	24 (17%)	3 (8%)
Missing	125	73	52
t(14,16)
No	84 (92%)	64 (94%)	23 (100%)
Yes	4 (8%)	4 (6%)	0 (0%)
Missing	212	145	67
t(11,14)
No	115 (81%)	88 (80%)	27 (84%)
Yes	27 (19%)	22 (20%)	5 (16%)
Missing	161	103	58
Gain 1q
No	66 (55%)	51 (54%)	15 (58%)
Yes	55 (45%)	44 (46%)	11 (42%)
Missing	182	118	64
Del(1p32)
No	90 (85%)	67 (82%)	23 (96%)
Yes	16 (15%)	15 (18%)	1 (4%)
Missing	197	131	66
Extra‐medullary disease
No	250 (88%)	176 (87%)	74 (93%)
Yes	33 (12%)	27 (13%)	6 (7%)
Missing	20	10	10
Para‐medullary disease
No	204 (74%)	150 (76%)	54 (70%)
Yes	70 (26%)	47 (24%)	23 (30%)
Missing	29	16	13
Plasmacytosis
No	244 (86%)	174 (85%)	70 (90%)
Yes	39 (14%)	31 (15%)	8 (10%)
Missing	20	8	12
Number of previous lines, median (min–max) [IQR]	4 (2–11) [3, 4, 5]	4 (2–11) [3, 4, 5]	4 (2–10) [3, 4, 5, 6]
Triple‐class exposed (at least 1 PI, 1 IMiD, 1 anti‐CD38)
No	8 (3%)	5 (2%)	3 (3%)
Yes	295 (97%)	208 (98%)	87 (97%)
Penta‐exposed (at least 2 PI, 2 IMiD, 1 anti‐CD38)
No	155 (51%)	98 (46%)	57 (63%)
Yes	148 (49%)	115 (54%)	33 (37%)
Triple‐class refractory (at least 1 PI, 1 IMiD, 1 anti‐CD38)
No/NA	147 (49%)	96 (45%)	51 (57%)
Yes	156 (51%)	117 (55%)	39 (43%)
Penta‐refractory (at least 2 PI, 2 IMiD, 1 anti‐CD38)
No/NA	233 (77%)	159 (75%)	74 (82%)
Yes	70 (23%)	54 (25%)	16 (18%)
Previous anti‐BCMA
No	262 (86%)	272 (81%)	80 (89%)
Yes	41 (14%)	31 (19%)	10 (11%)
ASCT
No	132 (44%)	64 (30%)	68 (76%)
Yes	171 (66%)	149 (70%)	22 (24%)
Median follow‐up, days, median (min–max) [IQR]	280 (5621) [119–399]	261 (8621) [92–391]	335 (5532) [221–410]
Response according to IMWG
Stringent CR	3 (1%)	2 (1%)	1 (1%)
CR	52 (18%)	38 (19%)	14 (16%)
VGPR	120 (42%)	79 (37%)	41 (46%)
PR	21 (7%)	11 (5%)	10 (11%)
SD	25 (9%)	17 (8%)	8 (9%)
PD	63 (22%)	49 (23%)	14 (16%)
NA	18	16	2
Treatment discontinuation > 1 months
No	232 (78%)	165 (79%)	67 (76%)
Yes	65 (22%)	44 (21%)	21 (24%)
Missing	6	4	2
Atypical Infection
No	241 (81%)	172 (88%)	69 (77%)
Yes	57 (19%)	36 (12%)	21 (23%)
Missing	5	5	0
Hospitalization due to infection
No	210 (71%)	146 (69%)	70 (78%)
Yes	87 (29%)	67 (31%)	20 (22%)
Missing	6	6	0
Polyvalent Immunoglobulin
No	106 (37%)	81 (41%)	25 (28%)
Yes	184 (63%)	121 (59%)	63 (72%)
Missing	13	11	2
Primary prophylaxis
No	62 (34%)	35 (34%)	12 (19%)
Yes	120 (66%)	69 (66%)	51 (81%)
Missing	121	94	27
Corticosteroids for CRS/ICANS
No	232 (79%)	157 (76%)	75 (85%)
Yes	62 (21%)	49 (24%)	13 (15%)
Missing	9	7	2
TOCILIZUMAB for CRS
No	218 (74%)	152 (75%)	66 (73%)
Yes	75 (26%)	51(25%)	24 (27%)
Missing	10	10	0

Both groups had received a median number of four prior lines of therapy, although a higher proportion of elderly patients had been exposed to ≥ 4 lines (64.7% vs. 55.4%, p = 0.13).

ECOG performance status was similar, with 39% of elderly and 36% of younger patients classified as frail (ECOG ≥ 2, p = 0.76). At the time of data cut‐off, mortality was lower in the elderly group (30.3% vs. 60.3%, p = 0.0145)

3.2. Disease Characteristics

Older patients displayed significantly fewer high‐risk cytogenetic abnormalities than younger patients (17% vs. 42%, p < 0.001). Rates of paramedullary disease, extramedullary disease and plasmacytosis were comparable. Nearly all patients were triple‐class‐exposed (97% vs. 98%), while fewer elderly patients were penta‐class‐exposed (37% vs. 54%). The proportions of triple‐class‐refractory disease were also comparable (43% vs. 55%).

Disease evolution was longer in the elderly compared to younger, mean disease evolution was 110.1 versus 86.6 months (p = 0.005).

Prior exposure to carfilzomib (87% vs. 62%, p < 0.0001), autologous stem cell transplantation (24% vs. 70%, p < 0.0001) and BCMA‐directed therapies (11% vs. 19%, p = 0.44) was less frequent among the elderly. The time from diagnosis to teclistamab initiation was longer in older patients (median 2664 days [7.3 years] vs. 2198 days [6 years], p = 0.012).

3.3. Efficacy

CR rates were slightly lower in the elderly (17% vs. 20%, RR = 1.04 [0.91–1.18]). However, when including very good partial response (VGPR), elderly patients achieved higher rates of deep responses (63% vs. 57%, RR = 0.7 [0.51–0.96]). ORR (≥ partial response [PR]), was significantly higher in the elderly group (74% vs. 62%, RR = 0.68 [0.41–1.04]), while progressive disease at first evaluation was less frequent (16% vs. 23%, RR = 0.7 [0.39–1.23]) (Figure 1).

FIGURE 1.

Response rate to teclistamab depending on age group.

PFS was superior in elderly patients, with a median of 15.1 months (95% CI, 13.7–17.7) compared with 12.4 months (95% CI, 8.9–13.9) in younger patients (p = 0.0134) (Figure 2A). Median OS was not reached in the elderly group, whereas it was 14.2 months (95% CI, 11.7–17.3) (p = 0.0074) (Figure 2B).

FIGURE 2.

Teclistamab PFS (top) and OS (bottom) according to age group.

Median follow‐up was also longer for elderly patients (335 vs. 261 days, p = 0.011).

The frailty analysis shows that efficacy is better for fit patients with an ORR (≥ PR) at 74% versus 59% as illustrated in Figure 3. OS is also better in this subgroup with an unreached OS for fit patients compared to 422 days (14 months) median OS (p = 0.02) in the frail group leading to an HR of 1.59 (1.07–2.34).

FIGURE 3.

Efficacy (left) and OS (right) for fit and frail patients.

3.4. Safety

The overall safety profile was comparable between groups. Severe ICANS or CRS requiring corticosteroids occurred less frequently in elderly patients (15% vs. 24%). Tocilizumab use was similar.

Treatment discontinuation rates did not differ significantly (24% vs. 21%). Infections occurred in both groups, with elderly patients more likely to experience atypical infections, such as Encephalitozoon intestinalis, hepatitis E, salmonellosis infections, multiple viral reactivations or infections such as Noroviruses (23% vs. 12%, p = 0.23) but requiring fewer hospitalizations (22% vs. 31%, p = 0.08). Notably, elderly patients were more frequently managed with primary prophylaxis (81% vs. 66%, p = 0.002) and polyvalent immunoglobulins (72% vs. 59%, p = 0.058).

4. Discussion

This real‐world study highlights the characteristics and outcomes of elderly patients (≥ 75 years) with R/R‐MM treated with teclistamab, reflecting the expected age distribution in a European context with an aging population. Approximately 30% of patients in our cohort were older than 75 years, a subgroup often underrepresented in clinical trials. Our data demonstrate that even elderly patients with comorbidities or heavily pre‐treated disease can achieve meaningful responses with bispecific antibody therapy.

In R/R‐MM, where multiple therapeutic options—including immunotherapies and cellular therapies—exist, evaluating treatment sequencing and patient selection is crucial. In our cohort, elderly patients treated with teclistamab showed superior PFS and OS compared to younger patients. This may be explained by less aggressive disease biology with fewer renal impairments, anaemia or hypercalcemia, fewer high‐risk cytogenetic abnormalities, long disease history with more treatment lines and lower prior exposure to certain treatments.

These findings are consistent with recent North American real‐world data [4], which included 22% of patients aged ≥ 75 years. In their cohort, the VGPR or better rate was 53%, with a median PFS of 10.7 months in the elderly, versus 5.2 months in younger patients, and OS not reached versus 16.1 months in younger patients. Notably, their patients were more heavily pre‐treated (median six prior lines) compared to our cohort (median four prior lines), which likely explains the relatively better outcomes observed in our elderly population.

Compared to the MajesTEC‐1 study, our real‐world cohort showed a CR rate of 17% in elderly and 20% in younger patients, with VGPR rates of 63% versus 57%, and an ORR (> PR) of 74% in the elderly. The median PFS in elderly patients (15.1 months) compares favourably with MajesTEC‐1.

This study aimed to analyse and explore the real‐life efficacy and toxicity of drugs in elderly patients, who are excluded from almost all clinical trials. Frailty analysis allows to look beyond age as the sole criterion and shows that frail patients have lower therapeutic efficacy, as previously described [6].

When compared to other bispecific antibodies, such as elranatamab, results are broadly similar. In the Phase II MagnetisMM‐3 study [7], VGPR or better was achieved in 56.1% of younger, highly pre‐treated patients. French real‐world data also showed a 42% rate VGPR or better response in younger patients with similar clinical conditions [8].

Moreover, recent studies comparing teclistamab with CAR‐T therapies in elderly patients (≥ 70 years) reported a median PFS of 13.1 months and OS not reached [9]. These data suggest comparable efficacy between teclistamab and CAR‐T in geriatric patients, with the advantages of lower cost, wider availability and outpatient administration.

Limitations of our study include its retrospective design, and heterogeneity in adverse event management. While the sample size of elderly patients is limited, this study provides meaningful real‐world insights that complement clinical trial data.

5. Conclusion

This real‐world analysis demonstrates that teclistamab is effective and well tolerated in elderly patients with R/R‐MM, including those who are heavily pre‐treated, frail or have comorbidities. Elderly patients represent a substantial proportion of real‐world teclistamab recipients and experience similar toxicity to younger patients, with significantly improved response rates and favourable PFS and OS outcomes. These findings support the use of teclistamab as a therapeutic option in the geriatric R/R‐MM population.

Author Contributions

A.C., C.H., A.P., designed the study. A.C., C.H., A.P. analysed the data. A.C. and A.P. wrote the paper. All authors interpreted the data and reviewed the manuscript. All authors included the patients.

Funding

The authors have nothing to report.

Conflicts of Interest

S. Manier: Consulting activities for AbbVie, Adaptive Biotechnology, Regeneron, Roche, SANOFI, TAKEDA. J. R. Eveillard received honoraria from Janssen and Sanofi and invitations to congresses from Janssen, Amgen. C. Touzeau: Honoraria and advisory boards: Janssen, Celgene/BMS, Takeda, Amgen, Sanofi, Pfizer, Abbvie. M. Mohty: Honoraria from Janssen, Sanofi, BMS, Amgen, Takeda, GSK, Pfizer, Novartis, Jazz pharmaceuticals, Stemline and Astellas. LM: Honoraria: Sanofi. FOP: Honoraria from and participates in the advisory board of Sanofi. L. Frenzel: consultant for Pfizer, Roche, CSL Berhing, SOBI, Biomarin. E. Chalayer: honoraria for lectures from Sanofi, Janssen, Amgen, Stemline, for advisory board participation from BMS, Sanofi, Stemline, Pfizer and Janssen and travel funding from Pfizer, Janssen and Sanofi. L. Vincent: Expert boards or bibliographic presentations or educational document writing for Janssen, BMS, Takeda, Sanofi; Congress fee funding: Janssen, BMS, Sanofi, Pfizer, Takeda. P. Moreau: Honoraria from and participates in advisory boards for Janssen, BMS, Takeda, Amgen, sanofi, Pfizer and AbbVie. C. Hulin: Consulting activities for Amgen, BMS, GSK, Janssen, SANOFI, TAKEDA. A. Perrot: Honoraria: Abbvie, Adaptive, Amgen, BMS, Janssen, Pfizer, Sanofi, Takeda. The authors declare no conflicts of interest.

Coste A., Godet S., Manier S., et al. “Teclistamab in Elderly Patients With Relapsed/Refractory Multiple Myeloma: A Subgroup Analysis of the French RetrosTECtive Cohort.” eJHaem 7, no. 1 (2026): e70233. 10.1002/jha2.70233

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.