Advantages of less frequent doing of BCMA-directed bispecific antibodies Free

The use of bispecific antibodies to treat relapsed/refractory myeloma has increased dramatically over the past several years. The reasons for this include their “off-the-shelf” availability and their efficacy even in triple class refractory myeloma and in patients who have already been treated with 5 prior lines of therapy, including prior stem cell transplant. Alternative schedules and fixed duration of treatment are being explored as a way to decrease toxicity, including infections, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as well as to address the issues of maintaining long-term effectiveness by decreasing T cell exhaustion. An additional burden of these treatments are their expense and requirement that patients have to go to clinic weekly or every other week.

We report a single institution experience of 10 patients with relapsed/refractory multiple myeloma, who were treated with BCMA-directed bispecific antibodies and who have gone on to monthly dosing. The median age of the patients was 68. All of the patients were triple class refractory with a median of 3.5 prior lines of therapy and with 8/10 patients having had a prior transplant.

Half of the patients were treated with teclistamab and half with elranatamab. The median time from diagnosis for these patients was 7 years (range 1-15 years). Patients were taken through the prescribed step up dosing and then advanced to every other week dosing. During this period, toxicity included infections, low-grade CRS and 1 case of low-grade ICANS. All of the patients achieved a CR or better by the time they reached every other week dosing.

The decision to go to monthly dosing was highly variable, including patient preference, physician preference, intercurrent medical procedures and insurance problems. The median time to go to monthly dosing from every other week dosing was 8 weeks. All ten patients maintained their complete response with monthly dosing. As of the time of this report, the median time on monthly dosing was less than 6 months (range 3-28 weeks).

No case of CRS or ICANS was reported during monthly dosing. All of the patients were begun on monthly IVIG after starting treatment with the bispecific antibodies. 2 patients who had frequent upper respiratory tract infections (URI's) prior to treatment with the bispecific antibodies had additional episodes of viral URI's during the monthly treatment. In the other patients, no new infections were reported; however, 1 patient was noted to have CMV reactivation.

Our experience similarly reflects that of a recent FDA approval of monthly dosing of elranatamab after at least 24 weeks of the bi-weekly (every two weeks) dosing regimen based upon the long-term update from the phase 2 Magnetis MM study. In a post-hoc analysis from that study, 96.2% of patients maintained their response and infections were reduced from 17.9% to 10.7%. As more experience and data are collected, we believe that less frequent dosing will become the norm.