The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody (bsAb) therapy in patients with relapsed refractory multiple myeloma
Lindsay Hammons,
Aniko Szabo,
Abhishek Janardan,
Vineel Bhatlapenumarthi,
Evanka Annyapu,
Binod Dhakal,
Samer Al Hadidi,
Sabarinath Venniyil Radhakrishnan,
Ravi Narra,
Divaya Bhutani,
Sharmilan Thanendrarajan,
Siegfried Janz,
Maurizio Zangari,
Suzanne Lentzsch,
Frits van Rhee,
Juan Carlos Rico Crescencio,
Anita D’Souza,
Rajshekhar Chakraborty,
Meera Mohan,
Carolina Schinke
Affiliations
Lindsay Hammons
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Aniko Szabo
Division of Biostatistics, Institute of Health and Equity, Medical College of Wisconsin, Milwaukee, WI
Abhishek Janardan
Medical College of Wisconsin Medical School, Milwaukee, WI
Vineel Bhatlapenumarthi
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Evanka Annyapu
Medical College of Wisconsin Medical School, Milwaukee, WI
Binod Dhakal
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Samer Al Hadidi
Myeloma Center, University of Arkansas for Medical Science, Little Rock, AR
Sabarinath Venniyil Radhakrishnan
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Ravi Narra
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Divaya Bhutani
Multiple Myeloma and Amyloidosis Program, Columbia University, Herbert Irving Comprehensive Cancer Center, NY
Sharmilan Thanendrarajan
Myeloma Center, University of Arkansas for Medical Science, Little Rock, AR
Siegfried Janz
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Maurizio Zangari
Myeloma Center, University of Arkansas for Medical Science, Little Rock, AR
Suzanne Lentzsch
Multiple Myeloma and Amyloidosis Program, Columbia University, Herbert Irving Comprehensive Cancer Center, NY
Frits van Rhee
Myeloma Center, University of Arkansas for Medical Science, Little Rock, AR
Juan Carlos Rico Crescencio
Internal Medicine, Division of Infection Disease, University of Arkansas for Medical Science, Little Rock, AR
Anita D’Souza
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Rajshekhar Chakraborty
Multiple Myeloma and Amyloidosis Program, Columbia University, Herbert Irving Comprehensive Cancer Center, NY
Meera Mohan
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Carolina Schinke
Myeloma Center, University of Arkansas for Medical Science, Little Rock, AR
There is a paucity of granular data on infection risk with B-cell maturation antigen (BMCA) and GPRC5D bispecific antibodies (bsAb) in relapsed/refractory multiple myeloma (RRMM). The aim of our multi-institutional study was to characterize the incidence, etiologies, and risk factors of infections from the start of therapy to the last follow-up or 90 days after study exit. A total of 66 patients received BCMA bsAb monotherapy, 15 GPRC5D bsAb monotherapy, and 15 GPRC5D bsAb combination therapy with daratumumab and/or pomalidomide. While the infection rate per 100 days was 0.57 for BCMA bsAb, it was 0.62 for GPRC5D bsAb combination and 0.13 for GPRC5D bsAb monotherapy; P=0.05. The proportion of infections that were grade ≥3 was higher in the BCMA bsAb group compared to the GPRC5D groups (58% vs. 36%; P=0.04). Grade 5 events were observed in 8% (n=8) of the patients, all treated with BCMA bsAb. The 9 month cumulative incidence of any grade of infection was similar in the BCMA and GPRC5D-combination groups (57% and 62%) and significantly higher than in the GPRC5D-mono group (16%); P=0.012. The cumulative incidence of grade ≥3 infections was highest in the BCMA group reaching 54% at 18 months; P=0.06. Multivariate analysis showed that BCMA bsAb therapy or GPRC5D combination therapy, history of previous infections, baseline lymphopenia, and baseline hypogammaglobulinemia were significantly associated with a higher risk of grade ≥3 infections. Our results indicate that BCMA bsAb and GPRC5D-combination therapies in RRMM are associated with higher cumulative incidence of infection and grade ≥3 infection compared to GPRC5D bsAb mono.