Abstract
Introduction:
Bispecific therapy is a novel immunotherapy directed against dual targets to enhance anti-tumor response in Multiple Myeloma (MM). In initial studies, patients with poor renal function were excluded from registration trials, creating a knowledge gap of safety and efficacy of these therapies in this subgroup. There has been growing real world evidence supporting the safety of bispecific therapy in patients with chronic kidney disease (CKD) stage 3b and above. In this study, we used a large database to evaluate outcomes in patients with MM and CKD receiving bispecific therapy.
Methods:
We conducted a retrospective study using the TrinetX Network database, comparing patients with MM and CKD 3b, 4 or 5, receiving bispecific therapy, Talquetamab, Teclisamab or Elranatamab to those with MM and no CKD above stage 3b, since their FDA approval in 2022. Incidence of all-cause mortality, Cytokine Release Syndrome (CRS), Immune effector Cell Associated Neurotoxicity Syndrome (ICANS) and development of dependence on dialysis in this subgroup was analyzed. This was also compared to those without CKD receiving bispecific therapy.
Results:
There were 116 patients with MM and CKD stage 3b and above, receiving Teclistamab (85), Talquetamab (16) and Elranatamab (10) exclusively. 93 of these patients were without dependence on dialysis before receiving either of these therapies. Those without dependence on dialysis were in the age range of 49-90 years. 52 were male, 40 were female and the gender was unknown for 10. Majority were White (46) or African American (31), rest were American Indians, Alaska natives, Asian, Native Hawaiian, Pacific Islander or unknown race. In this cohort, 25 patients died, with mortality risk 27.124% and survival probability of 65.26%. <10 had CRS or ICANS. Interestingly, no patients progressed to dependence on dialysis after initiation of bispecific therapy. There were 239 patients with MM without CKD who received bispecific therapy. In comparison with those with CKD, irrespective of dependence on dialysis and after propensity score matching, there was no difference in risk of mortality (p 0.91), development of CRS (p 0.66) or ICANS (p 0.86) between the two groups.
Conclusions:
Our study shows that the safety profile of bispecific therapies in MM is similar in patients with or without CKD, including those on dialysis. Our data bridges the uncertainty about side effects of bispecific therapy in patients with CKD. Our results also support the inclusion of this subgroup of patients in future trials evaluating bispecific therapies.
