Non-BCMA-Targeting Bispecifics in Multiple Myeloma: Cevostamab
A brief discussion on clinical trial data with cevostamab therapy followed by considerations for other non-BCMA-targeted agents being studied in the setting of multiple myeloma.
Transcript:
Josh Richter, MD: Moving on to newer targets, we’re going to talk about cevostamab, which targets FCRH5, another ubiquitously expressed antigen on myeloma cells. These are data that were presented from…the phase 1 study of cevostamab. This is administered as an intravenous drug. It has a step-up similar to the other bispecifics as has been described. The one notable difference about this study is for the moment, the lion’s share of therapy trials with bispecifics are giving the drug until progression or intolerable toxicity. The cevostamab study was designed for fixed-duration therapy, albeit 1 year of fixed duration. The drug is given every 3 weeks after the step-up for 17 cycles, which rounds out to about 1 year. On the study, the patients are allowed to be retreated at the time of progression while they’re in the observation phase after the 17 cycles.
So far, we’ve seen high levels of response. These are some of the data specifically focusing on those patients who have completed the 17 cycles and now remain on observation. We have patients ongoing in earlier cycles or those who have progressed before the 17 cycles. We see in this cohort, again small numbers so far, we have several patients achieving deep remissions like stringent CR [complete response] and CR, and several patients maintaining response off of therapy for a prolonged period of time, greater than 6 months, and in some cases greater than 12. To date, anyone who has completed the 17 cycles of cevostamab who had a stringent complete remission or greater in terms of their depth of response, has not yet relapsed off of therapy. This offers a chance to not only be off the drug, which is great for patients, but it may provide a chance for the T cells to regain some of their health for subsequent lines of therapy. In the world of T-cell redirection, the answer may not be gas pedal always to the floor; backing off a little may do something in terms of efficacy later and prevention of infectious complications.
We do see infections. In general, the infection risk seems to be somewhat lower in the non-BCMA bispecifics compared with the BCMA assets. Although, because you’re redirecting T cells from one job over here where they’re supposed to fight bacteria and viruses over to fight myeloma, you can still get infectious complications. So IVIG [intravenous immunoglobulin] may be needed for these patients as well. Interesting, as part of the study as Philippe had mentioned earlier, cohort E, which…presented at this past ASH [American Society of Hematology meeting], looked at giving prophylactic tocilizumab and reduced the rates of CRS [cytokine release syndrome] from over 90% to 38%. So far, again small numbers, this has not affected the response rate. We don’t know yet what this is going to mean long term, but it’s encouraging to move some of these drugs to the outpatient [setting].
There are several ongoing studies as with the other different assets. We have a number of the monumenTAL studies looking at combinations with talquetamab along with daratumumab and pomalidomide. We have the ongoing CAMMA studies, and specifically the CAMMA 2 study, which is looking at cevostamab, directly following patients who are progressing beyond an anti-BCMA therapy. The study is quite early on, but we’re hoping to gain some insight into optimal sequencing strategies. There are a number of other non-BCMA–targeting bispecifics so we have 3 here listed. RG6234 now goes by the fancy name forimtamig; I think they’re starting to change the naming policy. Phase 1 data were presented recently, a very interesting new drug, similar in many aspects to talquetamab, but so far only in phase 1. Now, we’ve used daratumumab for several years as a monoclonal antibody. There are 2 bispecifics, CD38, CD3 bispecifics, that have been studied. The AMG 424 study has been halted and to my knowledge is no longer proceeding in myeloma. However ISB 1342, previously known as GBR 1342, continues in the phase 1 dose-escalation studies, and we’re hoping to see more data as we get to more therapeutic cohorts.
Transcript edited for clarity.
