Table 3.
Literature summary of infection data from BsAb clinical trials in MM patients.
| Drug | Target | Study | Phase | Safety cohort N | No. of patients receiving RP2D n | Duration of treatment (range) | Infection AEs n (%) | Treatment-related infection AEs n (%) | Serious infection TEAEs n (%) | Infection AEs leading to discontinuation n (%) | Infection AEs resulting in death n (%) | Neutropenia n (%) | Lymphopenia n (%) | Leukopenia n (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Teclistamab | MajesTEC-1 [24] | I/II | 165a | 165 | 8.5 months (0.2–24.4) | Any grade: (76.4) | Any grade: – | – | 2 (1.21)b† | 16 (8.48%)c | Any grade: 117d (70.9) | Any grade: 57 (34.5%) | Any grade: 29 (17.6) | |
| Grade 3/4: (44.8) | Grade 3/4: – | Considered related: 4 (2.4) | Grade 3/4: 106 (64.2) | Grade 3/4: 54 (32.7) | Grade 3/4: 12 (7.3) | |||||||||
| BCMA x CD3 | MajesTEC-2 [40] (+daratumumab +lenalidomide) | Ib | 32e | 19 | – | Any grade: 29 (90.6) | – | – | 2 (6.3)f | 2 (6.3)g | Any grade: 27 (84.4) | Any grade: 4 (12.5) | – | |
| Grade 3/4: 12 (37.5) | Grade 3/4: 25 (78.1) | Grade 3/4: 4 (12.5) | ||||||||||||
| Elranatamab | BCMA x CD3 | MagnetisMM-1 [46–48] | I | 55h | – | – | – | – | – | – | 1 | Any grade: 41 (74.5)h | Any grade: 29 (52.7)h | Any grade: 19 (34.5)i |
| Grade 3/4: 15 (27.3) | Grade 3/4: 39 (71.0)h | Grade 3/4: 28 (51.0)h | Grade 3/4: 13 (23.7)i | |||||||||||
| MagnetisMM-3 [32] | II | 123j | 123 | 5.6 months (0.03–19.8) | Any grade: (66.7) | – | – | 8 (6.5) | 2 (1.6) | Any grade: 59 (48.0) | Any grade: 32 (26.0) | – | ||
| Grade 3/4: (35.0) | Grade 3/4: 59 (48.0) | Grade 3/4: 30 (24.4%) | ||||||||||||
| REGN5458 | BCMA x CD3 | LINKER-MM1 [110–113] | I/II | 68k | – | – | Any grade: (46.7)l | – | 1 (14.3%)m | – | 5 (6.85)k | Any grade: 17 (23)n | Any grade: 17 (23)n | – |
| Grade 3/4: (20.0)l | Considered related: 0k | Grade 3/4: 16 (22)n | Grade 3/4: 14 (19.2)n | – | ||||||||||
| Pavurutamab | BCMA x CD3 | NCT03287908 [114] | I/II | 75o | – | 6.1 weeks (3.1–15.3) | – | – | 13 (17%) | 1 | 2 (2.67) | Any grade: 23% | – | – |
| Considered related: 0 (0) | Grade 3/4: – | – | – | |||||||||||
| ABBV-383 | BCMA x CD3 | NCT03933735 [20, 49] | I/II | 174p | – | – | Grade ≥3: 39 (22) | – | – | – | 4 (3.2)q | Any grade: 60 (34) | Any grade: 45 (26) | – |
| Considered related: 0 (0) | Grade 3/4: 45 (26) | Grade 3/4: 41 (24) | – | |||||||||||
| Pacanalotamab | BCMA x CD3 | NCT02514239 [22] | I | 42 | 10 | – | Any grade: 14 (33) | – | 14 (33.3) | – | 2 (4.7)r | – | – | – |
| Grade 3–5: 10 (24.0) | ||||||||||||||
| Alnuctamab | BCMA x CD3 | NCT03486067 [34] | I | – | – | 14.0 weeks (1.6–46.0) | Grade 3/4: 30.0%s | – | 1s | – | – | Grade 3/4: 43%s | – | – |
| WVT078 | BCMA x CD3 | NCT04123418 [100] | I | 33t | – | – | – | – | – | – | – | Grade ≥3: 12.1% | Grade ≥3: 18.2% | – |
| Talquetamab | GPRC5D x CD3 | MonumenTAL-1 [9, 33, 37, 115] | I/II | 0.4 mg/kg QW: 143u | 288 | – | Any grade: 46.7%v | – | – | – | – | Any grade: 49 (34.3) | Any grade: 40 (28.0) | Any grade: 12 (40.0)v |
| Grade 3/4: 6.7%v | Grade 3/4: 44 (30.8) | Grade 3/4: 37 (25.9) | Grade 3/4: 9 (30.0)v | |||||||||||
| 0.8 mg/kg Q2W: 145u | Any grade: 38.6%v | – | – | – | Any grade: 41 (28.3) | Any grade: 38 (26.2) | Any grade: 10 (22.7)v | |||||||
| Grade 3/4: 9.1%v | Grade 3/4: 32 (22.1) | Grade 3/4: 37 (25.5) | Grade 3/4: 8 (18.2)t | |||||||||||
| RG6234 | GPRC5D x CD3 | NCT04557150 [35] | I | – | – | – | Any grade: 27 (52.9)w | – | – | 2 | 2 | Any grade: 12 (23.6)w | – | – |
| Grade 3/4: 9 (17.6)w | Grade 3/4: 6 (11.8)w | |||||||||||||
| Cevostamab | FcRH5 x CD3 | NCT03275103 [10] | I | 160x | – | – | Any grade: 68 (42.5) | – | – | – | – | Any grade: 29 (18.10) | – | – |
| Grade 3/4: 30 (18.8) | – | – | – | – | Grade 3/4: 26 (16.3) | – | – | |||||||
| Talquetamab + Daratumumab | GPRC5D x CD3 | TRIMM-2 [39] | Ib | 58 y | – | – | Any grade: 31 (53.4) | – | – | 1 (1.72)z† | Any grade: 19 (32.8) | Any grade: 15 (25.9) | – | |
| Grade 3/4: 10 (17.2) | – | – | Considered related: 1 (1.72) | Grade 3/4: 13 (22.4) | Grade 3/4: 15 (25.9) | |||||||||
| Teclistamab + Daratumumab | BCMA x CD3 | TRIMM-2 [38] | Ib | 65z | – | – | Any grade: 44 (67.7) | – | – | – | 3 (4.62)aa | Any grade: 32 (49.2) | – | – |
| Grade 3/4: 18 (27.7) | – | – | Considered related: 0 | Grade 3/4: 27 (41.5) | – | – |
Cells with no data are where data was not provided for the variable.
aData cutoff: 16 March 2022, median follow-up: 14.1 months. b1 due to Grade 3 adenoviral pneumonia, 1 due to Grade 4 PML. c12 due to COVID-19, 1 due to streptococcal pneumonia, 1 due to PML, 1 due to pneumonia, 1 due to pseudomonal pneumonia. d1 patient had a dose reduction due to recurrent neutropenia. 91 patients received G-CSF for neutropenia. eData cutoff: 17 Oct 2022. fBoth due to COVID-19. gOne due to COVID-19, one due to multi-organ failure due to sepsis. hData cutoff: 30 September 2022. Median follow-up: 12.0 months. iData cutoff: 26 July 2021. Median follow-up: 12.5 months (part 1), 7.5 months (part 1.1). jData cutoff: October 14, 2022. Median follow-up: 10.4 months. kData cutoff: 10 June 2021, median follow-up: 2.4 months. lInterim analysis, N = 45, Data cutoff: 15 June 2020, median follow-up: 2.37 months. mInterim analysis, N = 7, Data cutoff: 11 Oct 2019, follow-up range: 1.8–7.5 months. nUnknown data cutoff, safety population n = 73. oData cutoff: 2 July 2020, median follow-up: 1.7 months. pData cutoff: 16 Aug 2022, median follow-up: 14.1 months. qData cutoff: 8 Jan 2022, median follow-up: 10.8 months. In this data cutoff: three died due to COVID-19, one due to sepsis. rOne due to influenza/ aspergillosis, and one due to adenovirus-related hepatitis. sData cutoff: 28 October 2019. Median follow-up not provided. tData cutoff: 8 December 2021. Median follow-up not provided. uData cutoff 12 September 2022, median follow-up for 0.4 mg/kg: 14.9 months, for 0.8 mg/kg: 8.6 months. vData cutoff 6 Apr 2022, median follow-up for 0.4 mg/kg: 13.2 months, for 0.8 mg/kg: 7.7 months. wData cutoff: 5 Apr 2022. Median follow-up not provided. xData cutoff: 18 May 2021, median follow-up: 6.1 months. yData cutoff 6 April 2022, talquetamab median follow-up: 5.1 months, teclistamab median follow-up: 8.6 months. zDue to treatment-related pneumonia. aaDue to treatment-related bacterial pneumonia, sepsis, COVID-19, considered unrelated to treatment.
AE adverse event, BCMA B cell maturation agent, BsAb bispecific antibody, CD cluster of differentiation, FcRH5 Fc receptor-homolog 5 G-CSF granulocyte colony-stimulating factor, MM multiple myeloma, PML progressive multifocal leukoencephalopathy, Q2W once every 2 weeks, RP2D recommended Phase 2 dose, R/R relapsed/refractory, TEAE treatment-emergent adverse event.