Bispecific Antibody Therapy in Relapsed/Refractory Myeloma | Meera Mohan, MD, MS, FACP | ASCO 2023

Hello, I'm Meera Mohan. I'm one of the myeloma faculty at the Medical College of Wisconsin. Today I'll be discussing the work that we're presenting here at ASCO 2023. This is a multi-institution collaborative project exploring the infectious complications with bispecific antibody in patients with a relapsed refractory myeloma. So we know that bispecific antibody therapy in myeloma is associated with unprecedented clinical efficacy. The early phase one two studies have also signaled at an increased risk of infection, including higher rates of infection, higher rates of grade three infection, deaths secondary to infection. So our multi-institution collaborative project aims to understand the incidence, the etiology and possibly identify some of the risk factors associated with infection with use of this novel immunotherapy in patients with a relapsed refractory myeloma. So for this study, we pulled in three institutions, Medical College of Wisconsin, Columbia and University of Arkansas. So together we have about 90 patients treated with bispecific antibody therapy on various phase one two studies. A total of 96 treatment locations were used in the study. We observed that the majority of the patients were treated with bispecific antibodies targeting BCMA. And that's about 66 patients out of the 90 patients and about 30 patients received GPRC5D targeting antibodies. Half of these patients received GPRC5D antibody as a single agent or a monotherapy and half of them received GPRC5D antibody in combination with diatomumab plus or minus pomalidomide. What we found was that the rates of infection as expected was higher with BCMA targeting bispecific antibody and GPRC5D targeting bispecific antibody when used in combination with other agents. We noted an increased incidence of infections including great infections with BCMA bispecific as well as GPRC5D combination therapy compared to GPRC5D monotherapy. We also observed an 8% death secondary to infection. All of them occurred in patients who received BCMA targeting bispecific antibody. And majority of these patients were in an MRD negative complete response as far as their myeloma was concerned. Coming to the etiology of the infections, it was predominantly bacterial and viral with very few fungal infections reported. We also noted infections with rare bacteria in this cohort of patients. For instance, as we had a patient with pseudomonas bacteremia causing infection in the pericardial space, which is a space around the heart. And this was seen in that patient who got bispecific antibody for about 12 months and was in an MRD negative CR. In addition, we have rare about 3 to 4% of patients who had viral reactivations of common viruses such as CMV. There were also occasions where we noted rare viral infections such as norovirus infection, which is seen in patients who have gotten allotransplant. And in this particular patient's norovirus infection was severe to the point that he had persistent diarrhea for almost a year, requiring treatment discontinuation permanently. We looked also into what are the factors that can predict the risk of infection with use of this novel agents. And we found that baseline lymphopenia, which is low lymphocyte count at the start of therapy, hypogammaglobinemia, which is a low level of IgG defined as less than 400 in our study, use of BCMA targeting bispecific antibody and use of GPRC 5D targeting bispecific antibody, particularly in combination with other agents like diuretics or pomalidomide was independently associated with increased risk of infection and increased risk of grade 3 or higher infection, which is what we consider as severe infections. So overall, our study shows that infection risk in patients treated with bispecific antibody therapy is real. And we really need a more standardized way of monitoring and perhaps prophylactic measures to prevent infections in this setting. There are also ongoing studies investigating if an alternative dose or schedule of these therapies could mitigate the risk of infection. Thank you.