Retrospective Review Sheds Light on Real-World Efficacy With Teclistamab in R/R Myeloma After BCMA-Directed Therapy

Ariel F. Grajales-Cruz, MD

Teclistamab-cqyv (Tecvayli) produced objective response rates (ORRs) and complete response (CR) rates in real-world patients with relapsed and refractory multiple myeloma and prior exposure to BCMA-targeted therapy that were comparable to those achieved by patients enrolled in the phase 2 MajesTEC-1 study (NCT04557098) who had not received a prior BCMA-targeted agent, according to data from a single-center study presented at the 2023 ASH Annual Meeting.

In the retrospective chart review, data indicated that the ORR in patients who received teclistamab after a prior BCMA-targeted therapy (SOC group; n = 36) was 52.8% compared with 63% in those who had been enrolled in the clinical trial and had not previously received a BCMA-targeted therapy (MajesTEC-1 group; n = 165). Of those in the SOC group who had responded to treatment, 44.5% achieved a CR or better and 8.3% experienced a partial response (PR). Among the MajesTEC-1 responders, 39.4% achieved a CR or better, 19.4% had a very good PR, and 4.2% experienced a PR.

The progression-free survival (PFS) was 8 months (1.2-not reached [NR]) and the overall survival (OS) was NR (7.3-NR). Investigators did not find a statistical correlation between BCMA expression and PFS (P = .87) and OS (P = .57) outcomes. Patients who were heavily pretreated in that they had received 6 or more prior lines of therapy experienced inferior PFS (P = .0004) and OS (P = .002) data. A poor ECOG performance status, defined as 2 or higher, also negatively impacted PFS (P = .00087) and OS (P =< .0001).

“In our academic center, we wanted to explore real-world [data] vs what we saw in the original trial, the phase 1/2 MajesTEC-1 trial, that led to the [FDA] approval of teclistamab,” Ariel F. Grajales-Cruz, MD, an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center, stated in an interview with OncLive^®.

In the interview, Grajales-Cruz further discussed the real-world outcomes of heavily pretreated patients with relapsed or refractory multiple myeloma who received teclistamab at Moffitt Cancer Center and underscored future research efforts that will be needed to provide clarity on sequencing in the treatment paradigm.

OncLive: What prompted this investigation of teclistamab in relapsed/refractory multiple myeloma following BCMA-directed therapy?

Grajales-Cruz: Bispecific antibodies have become a very interesting therapeutic alternative for patients with relapsed/refractory myeloma. After CAR T-cell therapy, we did not have a lot of tools until bispecifics made their appearance. Now, we have 3: teclistamab, elranatamab-bcmm [Elrexfio], and talquetamab-tgvs [Talvey]. These [agents] have different targets; teclistamab [targets BCMA and CD3] elranatamab targets [LAG-3] and talquetamab targets GPRC5D.

[The [MajesTEC-1 trial], which evaluated teclistamab—the pertinent drug for this matter—did not include patients previously exposed to other BCMA-directed therapies. This remains a limitation [when translating the clinical data] to the real-world [setting]; the [variance] between clinical trials and what we have in the community. That’s why we wanted to [evaluate] real-world [data] vs what we saw in [MajesTEC-1].

What results were seen in the real-world population?

Since last year, we’ve treated patients with teclistamab. Out of these participants, 36 had received prior BCMA-directed therapies in the form of CAR T-cell therapy, antibody-drug conjugates [ADCs], or even other bispecific antibodies under a clinical trial. We were [trying to understand] the responses and toxicities of that approach in the real world.

We had good results and good outcomes that were comparable with [what was reported in] the original trial, with an ORR of 52.8% [in the real-world setting] compared with 63% in the original trial. However, we must take into consideration several factors, as well. We took patients who were more heavily pretreated than in the original trial and [we also] had patients with high-risk features. [In fact,] 44.1% of the patients had higher-risk features and there were frailer.

We even included patients who had an ECOG performance status over 2, which was not allowed in the [original] trial. Although we had a difficult-to-treat population altogether, we saw very comparable results.

Were there any subgroups of patients who were found to derive better outcomes with the agent than others?

Interestingly, the question [should be]: What patients did not do well? We thought that prior [receipt of] BCMA[-targeted therapy] was going to be a question mark for response rate. Turns out, it was not statistically significant, as these patients’ PFS was 8 months compared with the original trial, which was 11 [months; the difference] seems inferior.

However, the fact that they had prior BCMA-directed therapies was not very meaningful in that regard. It did not make a difference whether it was CAR T-cell therapy, an ADC, or other bispecifics [that they had received]. The responses were not dependent on the type of regimens and high-risk disease was not a predictor [for response] either, although performance status was. Patients who had an ECOG performance status of 2 or more did do worse and had a shorter PFS than everyone else.

What was observed regarding the safety of teclistamab in a real-world setting?

In the data that were reported, we did not see any new safety signals. As expected, cytokine release syndrome [CRS] was seen in some of these patients, although none of [these effects] were [higher] than grade 2. We saw no grade 3 or 4 [CRS]. There were [fewer instances of] CRS seen here compared with the clinical trial. It was very encouraging and was the same with neurotoxicity.

We saw less neurotoxicity than [what had been reported in] the pivotal trial. The toxicity that we [saw] was kind of expected. Infections remain a concern, and these patients live in a hypogammaglobulinemia state. We must consider the use of intravenous immunoglobulin when pertinent, as well as prophylactic drugs and antivirals for patients who also receive [teclistamab], especially because we found out that their CD4 count was in a good proportion at less than 200 [cells/mm³]. These patients are prone to acquiring opportunistic infections, such as pneumonia, and that’s why pentamidine is an important drug to consider for those patients as prophylaxis.

Where should research efforts focus going forward?

The big question that remains unanswered to some extent is sequencing. What is going to be the optimal sequence? We know from some of the work that [has been] presented recently that the responses to CAR T-cell therapy are not necessarily the same when patients have received prior BCMA-directed therapy. However, it seems that the other way around is not as relevant.

We still have good results and good responses [with] teclistamab in prior BCMA-directed therapy patient populations. However, now, it’s not only teclistamab, but also elranatamab and talquetamab. How do we sequence those therapies? That’s the next question [to answer in] the next couple of years, to be able to have a good sequence to have a very significant prolonged PFS and OS. Myeloma remains an incurable disease; however, now more than ever, it’s treatable. That’s going to be the question [to address over] the next couple of years.

Reference

Grajales-Cruz AF, Castaneda C, Hansen DK, et al. Teclistamab induces favorable responses in patients with relapsed and refractory multiple myeloma after prior BCMA-directed therapy. Blood. 2023;142(suppl 1):3351. doi:10.1182/blood-2023-184928