Real-World RRMM Data Explore Dose Deescalation and Outpatient Use of Teclistamab

Hana F. Safah, MD

Professor of Clinical Medicine

Section of Hematology and Medical Oncology

Director, Stem Cell Transplantation Program and the Leukemia and Lymphoma Programs

Tulane University School of Medicine

New Orleans, LA

Targeted Oncology: What data are there on the real-world use of the bispecific antibody teclistamab (Tecvayli) since its FDA approval for relapsed/refractory multiple myeloma (RRMM)?

Hana F. Safah, MD: The real-world characteristics on step-up dosing for teclistamab [from] the National All-Payer Claims Database looked at all patients who received teclistamab after teclistamab was approved by the FDA and received at least 1 dose, and they ended up with 182 patients.¹ They wanted to see the length of stay with the ramp-up and the treatment dose. We see that with time, the number of days of hospitalizations was getting fewer and fewer [from a mean 11.4 days through February 2023 to 7.0 days through July 2024]. It's because we know how to do it now and we started learning how to do it.

Then they wanted to see CRS [cytokine release syndrome] in the real world. When they looked at those patients who received the drug in the hospital, the rate of CRS was 41% and 30% of those were grade 1, [6.9%] grade 2, and 1.5% grade 3. Grade 2 is not something that is easy to take care of.

What do real-world data tell us about using a less frequent schedule for teclistamab?

[They wanted to know whether physicians] played around with the dosing in the real world. They looked at what they call the real-world deescalation. Remember, with teclistamab they gave it every week until progression. We don't do that all the time. We customize according to our patient [if] they don't want to come this week, they want to come every other week, or they're not tolerating the dose. We do things, and pharmacists saw what's happening in the real world. Then they can do a trial to tell you what happens with that.

Looking at what happens in the real world, at the median follow-up of 4.2 months, less frequent dosing was observed in 78 of 419 patients who received the drug.² So, 78 patients had less frequent dosing. When did they start giving less frequent dosing? At 3 months, it was 19%, at 6 months, 38.6%, and at 9 months, it was 46%. The longer [they were treated, the more] the physician started going down with the frequency of the dose. Now, did that affect the outcome? Looking at those patients, when they looked at time to next treatment, and they used that as a proxy to progression of disease, they saw that out of the 419 patients, 11.7% received a subsequent line of therapy, and out of those patients who received less frequent, or lower dose, only 3.8% received a subsequent line of therapy. So decreasing the frequency or decreasing the dose did not affect the outcome that much. I'm not going to say, ”Let’s do it this way.” I'm just saying, if it happens and you need to go down with frequency and dosing, if the patient pushes to do it, especially if they're showing evidence of response—not on ones who are showing stable disease or progression—but if they're starting to respond and continue responding.

The probability of receiving the next line of therapy at 3 months, for instance, is 6.4% [and 19.2% at 6 months, and 23.6% at 9 months]. The longer the time, the better the response with the deescalation of the dose.

[Another real-world study] is from Memorial Sloan Kettering Cancer Center [MSK].³ They started giving bispecific [antibodies to patients]. They grouped the patients into what they called early initiators, recent initiators, and patients with less frequent dosing. The early initiators were when the drug was available [by March 31, 2023]. They gave it for those patients who are not doing well, who had bulky disease. They wanted to get on a weekly basis. Then recent initiators…later on, they started including patients who were doing OK [treated after March 31, 2023]. [In those patients], they said, “Let's see if we can do every 2 weeks instead of every 1 week.” They planned on doing this less frequent dosing, and they followed all patients [n = 86]. When you look at the outcome from MSK, the overall response rate was similar in both groups [67% in early initiators, 57% in recent initiators]. The 6-month PFS was similar [53.3% and 52.3%, respectively], and the duration of 6-month duration of response was similar [70.0% and 82.1%, respectively]. It just tells you maybe it’s OK if we need to do it, we can go down with the dose, and we can go down with the frequency.

Can teclistamab be given in the outpatient setting from the start?

[The OPTec trial (NCT05972135)] asked, can we do the outpatient [administration] without admitting them for the step-up dosing? It's a small study with only 11 patients.⁴ They made them sign the consent form, and they gave them tocilizumab [Actemra] as a prophylaxis before the first dose. They started with the tocilizumab, and then they gave them the step-up dose, but they did it all as an outpatient. They gave them tocilizumab and they did the ramp-up in the clinic, and they then they went to the treatment dose of 1.5 mg/kg as outpatient up to 12 cycles until the end of the treatment.

When I read the article on the methods, they gave the patients equipment, like a tablet, so that they can communicate with the physician whenever they have a fever. They did not just let them go home [unattended]. They gave them the needed tools, and they educated them on how to use them. This is something for those patients who can do that. Not all our patients can utilize this. Some of them still have flip phones. But for those who can, it's an option. So they did that, and out of those 11 patients, they looked at CRS and other adverse events. The most common adverse events were headache [n = 5], nausea [n = 5], and neutropenia [n = 4]. In those 11 patients—in a very small patient population, so we cannot generalize—there was no CRS and no ICANS [immune effector cell–associated neurotoxicity syndrome]. When we look at the efficacy, 5 patients were in good remission, [4 of whom] had very good partial response.

There are real-world data looking at outpatient step-up dosing. They wanted to see; has it been done in the real-world data? They were able to collect data on 45 patients…. When you look at the CRS, CRS was seen in 28.9%, so it's not as high as the 70% [in the MajesTEC-1 trial (NCT03145181, NCT04557098)].^5,6 The majority of those were grade 1; there were very few grade 2. So, it can be done, it's just that it has to be done in the right place, in the right patient population with the right education.

_References:

_{1. Banerjee R, Kim N, Kohli M, et al. Evolving real-world characteristics and step-up dosing among early initiators of teclistamab for multiple myeloma - a national all-payer claims database study. Blood. 2023;142(suppl 1):5087. doi:10.1182/blood-2023-178908}

_{2. Pianko MJ, He J, Lin D, et al. Real-world schedule de-escalation of teclistamab in patients with relapsed or refractory multiple myeloma – a US national healthcare claims analysis. Presented at: 29th European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P990. Accessed November 15, 2024. https://library.ehaweb.org/eha/2024/eha2024-congress/document?c_id=421054&cm_id=435887&type=document435887}

_{3. Tan C, Derkach A, Maclachlan K, et al. Real-world schedule de-escalation of teclistamab in patients with relapsed/refractory multiple myeloma. Presented at: 29th European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P902. Accessed November 15, 2024. https://library.ehaweb.org/eha/2024/eha2024-congress/420966/}

_{4. Rifkin RA, Schade HH, Simmons G, et al. OPTec: A phase 2 study to evaluate outpatient (OP) step-up administration of teclistamab (Tec), a BCMA-targeting bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;42(suppl_16):7528. doi:10.1200/JCO.2024.42.16_suppl.7528}

_{5. Sandahl TB, Soefje SA, Calay ES, et al. Real-world treatment outcomes of teclistamab under an outpatient model for step-up dosing administration. Blood. 2023;142(suppl 1):5154. doi:10.1182/blood-2023-174270}

_{6. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478}