medwireNews: A retrospective analysis has shown an association between use of intravenous immunoglobulin (IVIg) and a reduced risk for grade 3–5 infections in people with multiple myeloma receiving bispecific antibodies targeting B-cell maturation antigen (BCMA).
The incidence was reduced by a significant 90% during periods of Ig replacement, report Guido Lancman (Princess Margaret Cancer Centre, Toronto, Ontario, Canada) and collaborators in Blood Cancer Discovery.
“Pending confirmation in other datasets and ideally in randomized prospective studies, these results provide a strong rationale for primary prophylaxis with IVIg or subcutaneous Ig in these patients,” they add.
The authors of a related commentary agree, saying that “these results support universal use of IGRT [immunoglobulin replacement therapy] in patients with relapsed/refractory multiple myeloma receiving anti-BCMA [bispecific antibody] therapy.”
Alfred Garfall and Edward Stadtmauer, both from the University of Pennsylvania in Philadelphia, USA, continue: “Although such a small, retrospective study would not ordinarily be the basis for clinical practice recommendations, these results affirm the impressions of clinicians with experience using these agents in clinical trials as reflected in two recent consensus statements that recommend universal use of IGRT in these patients.”
For the study, the researchers reviewed the records of 37 patients with multiple myeloma treated at Mount Sinai Hospital in New York, USA, with an anti-BCMA bispecific antibody as monotherapy in four clinical trials between January 2019 and June 2022. Participants were aged a median of 66 years and 62% were women.
A total of 41% of patients had an infection of grade 3 or worse, two of whom had a grade 5 event – one case each of COVID-19 and sepsis.
Lancman and colleagues highlight that there was “no plateau in cumulative infection risk over time,” and although the types of infection and the incidence “varied over time,” the rates “remained high even after more than one year on therapy.”
Moreover, the large majority (84%) of infections occurred during periods of disease control, indicating that “the treatment, rather than the underlying disease, is responsible for much of the immunosuppression through an on-target off-tumor effect,” they write.
The team also found that severe hypogammaglobulinemia (defined as IgG <200 mg/dL) was present in all 26 participants who responded to BCMA-targeted therapy, and 92% received IVIg at any point at the investigator’s decision.
Of note, the rate of grade 3–5 infections was significantly lower during periods when patients were receiving IGRT than when they were not, at an incidence rate ratio of 0.10. But there was no significant difference with respect to all-grade infections.
The commentators say that “Lancman and colleagues appropriately scrutinize infection risk with a single treatment modality in late-line multiple myeloma therapy,” but “this only scratches the surface.”
Garfall and Stadtmauer add: “We must wholistically consider cumulative infection risk across multiple lines of therapy, risks of other immune-related complications such as autoimmunity, and perturbation of immune surveillance against other malignancies.
“Optimizing myeloma control and immune health may require strategic breaks in therapy for immune reconstitution and vaccination in addition to risk-adapted prophylaxis.”
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Blood Cancer Discov 2023; doi:10.1158/2643-3230.BCD-23-0049
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