Appropriately De-Escalating Talquetamab to Monthly Dosing in Multiple Myeloma

The expert panel

An unusual patient case was presented during a Frontline Forum where experts worked through how to appropriately treat a patient who was having consistent fevers and pain. The panel spoke about the de-escalation of treatment and when clinicians should consider doing so.

The patient case highlighted relapse along with responses, and adverse effects (AEs) that left the treating physician puzzled about how to proceed with subsequent lines of therapy. Read on to see how the panel discussed the next best approach and what to do for this patient.

The patient case

The patient case continued

As the case was being presented, Mikhael questioned whether bridging occurred during the 6 lines of treatment outlined. Gregory noted that she was only able to go back to using pomalidomide (Pomalyst) plus dexamethasone. She did highlight that she had never had a patient hit a complete response and then continue to progression 9 months later, which was “unusual” to her.

The case was also unusual in that once the patient received talquetamab-
tgvs (Talvey), he began to have severe fevers, which were similar to grade 1 cytokine release syndrome (CRS), and continued bone pain after every dose of talquetamab. Gregory found out that a predose of 40 mg of prednisone before talquetamab helped to mitigate those severe AEs.

Gregory asked her colleagues at what point she should de-escalate treatment to once a month, and whether she should continue premedicating him. She hypothesized he may experience immune fatigue.

Richard has had patients who have this CRS-like response from pomalidomide treatment. Even though this occurred before she began pomalidomide, she still believes it could be an instigator. In those situations, she began to give pomalidomide at 1 mg 3 times a week to lessen these AEs.

Gregory asked what to do about steroid use and whether Richard had acquired a “sweet spot” for dosing.

“There’s just no specific way. What I do sometimes is just give a tiny dose of dexamethasone, for day 2 and day 3. Everybody’s different, right? Sometimes I’ve just tried maybe 4 mg [twice a day] of dexamethasone or a onetime [dose of] 8 mg. I have to say I don’t have a particular standard. If they have a big tumor flare each time, I might do a 10-mg onetime dose and that seems to take away the fever and the bone flare,” Richard said.

Al Hadidi asked whether Gregory’s patient was experiencing any other AEs like taste issues or skin toxicities related
to CRS. Gregory responded that his skin had been fine
and around cycle 4 his taste began to improve, which is
typical. Of note, he has more of an appetite and is no longer losing weight.

Al Hadidi did sympathize with Gregory but noted that a once-a-month dose may help to decrease these AEs. He noted that patients who do tend to relapse on talquetamab do it regardless of the dosing frequency. He would recommend going down to once a month since there is a partial response and it could help with the low-grade CRS.

At Vanderbilt, Baljevic will try to de-escalate talquetamab and other bispecific antibodies as soon as possible. With data to back it up, he believes the patient should be switched to monthly talquetamab. He suggested exploring the use of dexamethasone to become more liberal with the premedication management.

As the case discussion concluded, Mikhael let Gregory ponder whether pomalidomide should be the correct treatment option for this patient. He did highlight there were many options in the space to choose from that might not be so impactful regarding AEs.

“In summary, this is helping us understand that although CRS in the vast majority of our patients is not something we have to think about after a few cycles, there are people, and we’ve seen this all along the way—for those of you who have enough gray hair, in the early days of rituximab [Rituxan], daratumumab [Darzalex], and others. There are some patients who continue to have that. I’m just glad you’ve been able to wean him off the tocilizumab,” Mikhael concluded.