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Войти в исследования P1518: INFECTIONS FOLLOWING BISPECIFIC ANTIBODIES IN MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS
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Abstract Topic: 30. Infections in hematology (incl. supportive care/therapy)
Background: Improved understand of infection risk amongst myeloma (MM) patients (pts) treated with bispecific antibodies (BsAbs) against plasma cell (PC) antigens BCMA, GPR5, FcRH5 is required.
Aims: We conducted a systematic review and meta-analysis to evaluate infection rates amongst MM pts receiving BsAbs.
Methods: A systematic literature search used Medline, Clinicaltrials.gov, Cochrane, Google Scholar, Embase, and major conference abstracts, with MeSH auto-exploded keywords for “multiple myeloma” AND “bispecific antibody” or “BiTE”. We included trials and abstracts published prior to Jan 26 2023 reporting infectious adverse events in English. Meta-analysis of proportions estimated pooled infection incidence using random effect models (Mantel-Haenszel) in R-4.2.2.
Results: 799 studies were screened and 6 Phase 1 and 6 phase 2 clinical trials included (N = 1409 pts, median age 64.5 years). 52% of pts (95%CI: 44-59%) experienced an infection of any grade. 23% of patients (95%CI: 17-29%) experienced a Grade ≥ 3 infection. Severe infections were higher amongst BCMA-treated pts (N = 807, 27%, 95%CI: 19 – 35%), compared to GPRCD5-treated pts (N = 442, 18%, 95%CI: 12-23%), but did not differ for all-grade infections (52 vs. 53%). Grade ≥ 3 neutropenia occurred in 29% of pts.
Summary/Conclusion: Despite promising efficacy in MM, BsAbs may come with substantial infection risk, warranting more detailed analysis of infections and immune phenotyping to guide targeted supportive care.
Table – Summary of included studies
| Agent | Target | Source | Phase | Enrolment (mm/yy) | N | Median prior lines | All-Grade Infection N (%) | Grade ≥3 Infection N (%) | Grade 5 Infections N (%) | Grade ≥3 CRS N (%) | ORR % | ≥VGPRR % | Median DOR months | Median Follow-up months (Range) |
| Alnuctamab (CC-93269) | BCMA | Wong 2022 | I | 03/18- | 68 | 4 | 23 (34) | 6 (9) | 0 | 0 | 53 | 40 | NR | 4.1 |
| ABBV-383 | BCMA | Voorhees 2022 | I | 10/22- | 174 | 5 | 61/124 (50) | 39/124 (22) | 8/124 (6.5) | 1 (0.5) | 59 | 44 | 9 | 6.8 (0.9 – 33.7) |
| Elranatamab | BCMA | Raje 2022 | I | 10/21- | 123 | 5 | 82 (67) | 43 (35) | 6 (5) | 0 | 61 | 55 | 17 | 10.4 (0.3-29) |
| Linvoseltamab (REGN545) | BCMA | Bumma 2022 | Ib/II | 1/19- | 252 | 5 | 136 (54) | 73 (29) | 10 (4) | 2 (1) | 57 | 42 | NR | 3.2 |
| Pacanalotamab (AMG-420) | BCMA | Topp 2020 | I | 3/19 – 4/22 | 42 | 5 | 14 (33) | 10 (24) | 2 (5) | 1 (2.4) | 70 | 60 | 9 | NR |
| Teclistamab | BCMA | Moreau 2022 | I/II | 09/20- | 165 | 5 | 126 (77) | 57 (45) | 12 (7) | 1 (0.6) | 63 | 55 | 18.4 | 14.1 |
| Teclistamab + daratumumab | BCMA + CD38 | Rodriguez-Otero 2022 | II | 03/21- | 46 | 5 | 29 (63) | 8 (17) | 0 | 0 | 78 | 73 | Not reached | 3.6 (0.1–10.4) |
| Forimtamig (RG6234) | GPRC5D | Carlo-Stella 2022 | I | 11/20- | IV: 51 SC: 57 | IV: 5 SC: 4 | IV: 31 (61) SC: 26 (46) | IV:11 (22) SC:15 (27) | IV: 1 (2) SC: 1 (2) | IV: 1 (2) SC: 1 (1.9) | IV: 71 SC: 64 | IV: 59 SC: 53 | IV: 10.8 SC: 12.5 | IV: 11.6 SC: 8.0 |
| Talquetamab | GPRC5D | Chari 2022 | I/II | 02/21- | 288 | 5 | 153 (53) | 46 (16) | 2 (0.7) | 2 (1.8) | 73 | 58 | 0.4mg: 10.2 0.8mg: 7.8 | 0.4mg: 14.9 0.8mg: 8.6 |
| Talquetamab + daratumumab | GPRC5D + CD38 | Van de Donk 2022 | II | 09/21- | 46 | 5 | 23 (50) | 6 (13) | 0 | 0 | 77 | 65 | Not reached | NR |
| Cevostamab (BFCR4350A) | FcRH5 | Trudel 2021 | I | 07/21- | 161 | 6 | 68 (43) | 18 (11) | 0 | 2 (1) | 90mg: 36 160mg:57 | 90mg: 21 160mg:33 | 90mg: 11.5 160mg NR | 90mg: 14.3 160mg: 6.5 |
Keywords: Bispecific, Multiple myeloma, Cellular therapy
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