For patients on commercial teclistamab who achieve a response, are there patient-specific or response-specific parameters that would prompt you to de-escalate therapy from once per week?
What dose and frequency of teclistamab do you use after achieving at least a PR from treatment for patients with relapsed/refractory multiple myeloma?
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I think it’s safe to say we really lack good evidence to guide us.
However, we must balance the risk of persistent immunosuppression with teclistamab and its efficacy.
The only piece of data I am aware of in this regard comes from ASCO 2023 in an abstract by @Dr. First Last.
In the MajesTEC-1 study, patients had the option to switch to Q2W dosing if patients achieved a confirmed partial response or better after ≥4 cycles of treatment (phase 1) or a confirmed complete response (CR) or better for ≥6 months (phase 2). At median 11.1-month (range, 2–24) follow-up since switching, the median duration of response from the date of switch was 20.5 months (range, 1–23), and 13/60 had progressed.
All in all, I think this makes a great case for switching to q2week dosing once a CR is achieved. I am very interested in the idea of drug holiday for patients with MRD negativity or perhaps some version of sustained MRD negativity. But we still need more data to compare these strategies.
We have started to de-escalate quickly, particularly for our elderly patients, who are having more difficulty tolerating teclistamab. Once the patients achieve at least a PR (which seems to be apparent within 2 cycles), we have been moving to q 2 weeks and even monthly, with what appears to be better tolerance. Agree with Dr. @Dr. First Last that this approach has not been studied.
I reviewed the investigator brochure for all the FDA-approved bispecific antibodies, and saw very little pharmacokinetic (PK) or pharmacodynamic (PD) data.
Hence, for patients that achieve a ≥VGPR after 1 month of weekly treatment, it's appealing to switch to monthly dosing for BCMA-directed bispecific antibodies. The majority of patients that respond will have ≥VGPR, and my experience with the PRs has not been positive.
I can't wait for better PK/PD data.
Responses are rapid (median time is just over 1 cycle) with teclistamab. Usually by 2 months, the patients are >PR (or VGPR), and I change them to biweekly. By 4 months (median in study is ~ 6 months to CR), the patients have reached a plateau in response, and I change them to monthly. Subsequently, I often change to every 2-3 months after a year of therapy.