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1005 Cumulative Incidence and Characteristics of Infections Requiring Treatment, Delay in Treatment Administration or Hospitalisation in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti BCMA or Anti GPRC5D Bispecific Antibodies

Program: Oral and Poster Abstracts
Type: Oral
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Predicting Outcome and Side Effects of Novel Immunotherapies in Multiple Myeloma
Hematology Disease Topics & Pathways:
adult, Biological therapies, Research, Bispecific Antibody Therapy, epidemiology, Clinical Research, Therapies, Adverse Events, Human, Study Population
Monday, December 11, 2023: 5:00 PM

Elise Cellerin1*, Aurelie Jourdes2*, Xavier Brousse3*, Nicolas Vallet4*, Tom Cartau5*, Blandine Denis, MD6*, Stephanie Harel, MD7*, Simon Jamard8*, Alexis Redor9*, Titouan Cazaubiel10*, Virginie Roland11*, Carine Caleteix12*, Morgane Charles12*, Pierre Berger13*, Guillaume Escure14*, Aude Collignon13*, Emmanuel Faure15*, Clarisse Cazelles16*, Fanny Lanternier17*, Clementine de La Porte Des Vaux18*, Laurent Frenzel, MD, PhD19*, Mathieu Blot20*, Francois Danion21*, Cécile Sonntag, MD22*, Cyrille Touzeau, MD, PhD23*, Andrea Pieragostini24*, Florence Ader25*, Lionel Karlin26*, Margaret Macro, MD27*, Guillaume martin-Blondel, PHD28*, Thomas Chalopin, MD29* and Aurore Perrot, MD, PhD30

1Centre hospitalier universitaire de Tours, Hospital, Tours, France
2Centre hospitalier universitaire de Toulouse, Hospital, Toulouse, France
3Infectiology, CHU de Bordeaux, Bordeaux, France
4Centre Hospitalier Universitaire de Tours/Service d'hématologie et thérapie cellulaire, Université de Tours, Tours, France
5Centre hospitalo-universitaire de Caen, Caen, France
6Infectious diseases, Saint Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
7Saint Louis Hospital, Paris, France
8Centre Hospitalier Universitaire de Tours/Service d'infectiologie et maladie tropicale, Centre Hospitalier Université de Tours, Tours, France
9Centre hospitalier de Perpignan, Centre hospitalier de Perpignan, Perpignan, France
10CHU De Bordeaux, Bordeaux, FRA
12Centre hospitalier de Perpignan, Perpignan, France
13Centre hospitalier et universitaire de Marseille, Marseille, France
14Centre Hospitalo-universitaire de Lille, Lille, French Guiana
15centre hospitalo-universitaire de Lille, Lille, FRA
16Hopital Necker, Paris, FRA
17Assistance Publique-hôPitaux De Paris (AP-HP), HôPital Necker Enfa, Paris, FRA
18Hopital Necker, paris, France
19Department of Haematology, Institut Necker, Paris, FRA
20Centre hospitalo-universitaire de Dijon, Dijon, France
21Centre hospitalo-universitaire de Strasbourg, Strasbourg, France
22Centre Hospitalier Universitaire Hautepierre, Strasbourg, FRA
23Centre Hospitalier Universitaire de Nantes, Nantes, France
24Hematology, CHU Dijon, Dijon, France
25Centre hospitalo-universitaire de Lyon, Lyon, France
26Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
27Hopital Cote De Nacre, Caen, France
28Centre hospitalier universitaire de Toulouse, Centre hospital-universitaire de Toulouse, Toulouse, France
29Centre hospitalier universitaire de Tours, Hospital, Tours, FRA
30Service Hematologie, CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d’Hématologie, Toulouse, France

Background. Bispecific antibodies (BsAb) are a new effective treatment for relapsed/refractory multiple myeloma (RRMM). Although these immunotherapies are well tolerated, infectious complications emerged as a predominant issue, mainly with anti-BCMA BsAb. Recent guidelines were presented to prevent and manage these complications based on clinical trials safety signals. In this study, we aimed to report incidence and characteristics of infectious complications in patients treated with anti-BCMA and anti-GPRC5D BsAb.

Methods. A retrospective study was conducted in 13 tertiary centers including patients with RRMM treated by BsAb between December 2020 and February 2023. We reported infectious complications events requiring specific treatment, delay in BsAb administration or hospitalisation and occurring up to three months after interruption of treatment.

Results. Among the 229 patients included, 200 (87%) received an anti-BCMA BsAb with teclistamab (n=153, ­67%) or elranatamab (n=47, 20%) and 29 patients (13%) received an anti-GPRC5D BsAb with talquetamab. 40% (n=90) of patients were treated in monotherapy, 42% (n=94) had dexamethasone in addition to the BsAb after step up doses and 18% (n=41) received a combination with an anti CD38, immunomodulatory treatment, proteasome inhibitor or other. The median age was 67 years (range 38-85), median of prior line of therapy was 4 (range 0-15). 62 (32%) patients had a high cytogenetic risk and 187 (82%) had a triple refractory disease.

With a median follow up of 7 months (IQR 4-12 months), 234 infectious events were documented in 142 patients (62%) including 53% grade ≥ 3 and 8.4% (n=19) deaths due to infection. All infections grade ≥ 4 (n= 48; 20.6%) occurred in patients treated with anti-BCMA BsAb.
Predominant localisation was pulmonary tract (n= 97, 41%) and disseminated infection (n=52, 22%). Among the documented infections, 91 (55%) were bacterial, 64 (39%) were viral and 8 (5%) were fungal (Figure 1A). Two (1.2%) infectious events were from a parasite. Most frequent pathogens were Enterobacteriaceae (n=28, 12%), SARS-CoV-2 (n=19, 8%), anaerobic bacteria (n=10, 4%) Pseudomonas aeroginosa (n=6, 2.5%). Invasive pulmonary aspergillosis was found in 6 (2.5%) patients, and 2 (1.2%) event was PML (progressive multifocal leukoencephalopathy) and 1 (0.6%) was disseminated toxoplasmosis.

Hospitalization rate was 57% (n=131), including 13% (n=30) requiring intensive care with a median hospitalization time of 10 (range 1-111) days. Overall, n=113 (47%) of the infectious events had an impact on the course of treatment. Illustrated by interruption in n=31 (14%) events, delayed administration in n=70 (32%) events or change in frequency of administration in 2 (0.9%) events.

Considering immunosuppression, 125 (68%) of these infections occurred in patients associated with hypogammaglobulinemia (<3 g/L) and 22% (n=50) in patients supplemented with intravenous immunoglobulin. Regarding infectious prophylaxis, n=104 (47%) infectious events occurred despite a bacterial prophylaxis (n=104), 91% (n=125) occurred under viral prophylaxis, 73% (n=166) with trimethoprim-sulfamethoxazole or atovaquone and 11% (n=25) with pentamidine use.

Global cumulative incidence of first infection was 70% in all patients, 73% in patients treated with
anti-BCMA and 51% with anti-GPR5CD. Treatment with anti-GPRC5D BsAb was independently
associated with a lower risk of first infection in a multivariate model adjusted for infectious
prophylaxis, and hypogammaglobulinemia, HR 0.43 (IC95% 0.23; 0.77); p=0.005 (Figure 1B).

Conclusion. This study highlights the rate of infectious event with BsAb treatment in RRMM setting. We describe higher frequency of infections in patients receiving anti-BCMA agents compare to anti-GPRC5D group. Impact on treatment administration is huge and dosing intervals strategy and prophylaxis appear necessary and effective to improve the morbidity and mortality rate of this hightly effective agents.

Disclosures: Frenzel: Pfizer: Consultancy, Other: Grant, Research Funding; Biomarin: Consultancy; Roche: Consultancy; CSL Berhing: Consultancy, Research Funding. Sonntag: Janssen, Takeda, BMS and Sanofi: Membership on an entity's Board of Directors or advisory committees. Touzeau: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Karlin: Amgen, Celgene, GSK, Janssen, Takeda: Consultancy; AbbVie, Amgen, Celgene, Janssen, Sanofi, Takeda: Honoraria. Macro: Janssen, Takeda: Honoraria, Other: Travel/accommodation, Research Funding; GSK, Sanofi: Honoraria. Perrot: Abbvie, Adaptive, Amgen, BMS, Janssen, Pfizer, Sanofi, Takeda: Honoraria.

*signifies non-member of ASH