Teclistamab Elicits Survival Benefit vs Real-World Treatment in Multiple Myeloma

Amrita Krishnan, MD

Teclistamab demonstrated superiority over physician’s choice of therapy for overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT) in patients with relapsed/refractory multiple myeloma.

In the study comparing the efficacy of teclistamab with physician’s choice of treatment in the real-world setting in patients with triple-class exposed, relapsed/refractory multiple myeloma, teclistamab induced a PFS of 10.05 months (95% CI, 8.05-not reached [NR]) vs 3.38 months (95% CI, 3.02-4.30) with physician’s choice of therapy (HR, 0.42; 95% CI, 0.30-0.58; P < .0001). OS was 18.3 months (95% CI, 18.3-NR) in patients treated with teclistamab vs 13.2 months (95% CI, 10.6-18.7) in patients from the real-world study (HR, 0.67; 95% CI, 0.43-1.05; P = .0829).1

Furthermore, the TTNT was NR (95% CI, 10.81-NR) with teclistamab vs 4.40 months (95% CI, 3.52-5.36) with physician’s choice of therapy (HR, 0.39; 95% CI, 0.28-0.55; P < .0001).

Lead study author Amrita Krishnan, MD, said these results highlight the therapeutic potential of the BCMA- and CD3-directed bispecific antibody in a heavily pretreated population. “[Exciting new treatments are emerging] with T-cell directed therapies, such as CAR T cells, as well as a new class of drugs, bispecific antibodies, which are T-cell–redirecting and myeloma cell–targeting,” she said.

In an interview with OncLive®, Krishnan discussed the findings from this study. She also emphasized larger efficacy and safety data regarding teclistamab and other bispecific antibodies in multiple myeloma, particularly highlighting the importance of infection control in this patient population.

Krishnan is the director of the Judy and Bernard Briskin Center for Multiple Myeloma Research and professor and chief of the Division of Multiple Myeloma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

OncLive^®: What was the rationale for the study?

Krishnan: Patients who have relapsed myeloma are a challenging group, and the challenge has become even greater now, as we have patients who relapse after increasingly effective therapies. The triple-class exposed, refractory patients who have relapsed after proteasome inhibitors, immunomodulatory agents [IMiDs], and anti-CD38 monoclonal antibodies are especially challenging.

The MAMMOTH study [NCT01985126] showed that the OS for patients who become refractory to an anti-CD38 antibody is quite short—less than a year. There’s a tremendous need for new therapies for those patients.

[Our study looked at data with teclistamab from the phase 2 MajesTEC-1 trial (NCT04557098)] and compared it with [information from the] real-world Flatiron Health Database. This study tried to match the key eligibility criteria of the MajesTEC-1 study of teclistamab specifically in terms of creatinine, lines of therapy, and timing of relapse from prior therapy.

Within the limitations of a retrospective database study, this study showed that [patients treated with] teclistamab had improved PFS, OS, and TTNT compared with patients in the real-world database cohort [who were treated with physician’s choice of therapy].

How might updated data from the MajesTEC-1 trial influence future steps with teclistamab?

Further updates of the MajesTEC-1 study suggest durability of responses in patients on teclistamab. No new safety signals [have been seen] as we’ve had more experience with the drug.

As we see more patients on teclistamab and other bispecific antibodies, [one notable aspect of these treatments] is the infection signal. We should bear this in mind as we optimize prophylaxis for those patients.

Some challenges were with COVID-19 as well, such as deaths from COVID-19 on trials with bispecific antibodies. We need to optimize preventative and prophylactic measures against infection, including COVID-19.

What next steps could follow from this research?

Myeloma drugs are usually tested in the advanced refractory setting. Once efficacy and safety are established, those drugs are then rapidly tested in combinations. Many ongoing trials are combining teclistamab with drugs such as pomalidomide [Pomalyst] and daratumumab [Darzalex].

Ongoing trials are also using teclistamab earlier in the course of disease, such as comparing it with daratumumab plus pomalidomide and dexamethasone or daratumumab plus bortezomib [Velcade] and dexamethasone. Teclistamab can certainly be used earlier and defining optimum sequencing and combinations with these drugs is going to be important.

What additional safety data with teclistamab are important to note?

Safety findings are generally similar across bispecific antibodies, with the exception of talquetamab. [Most of these agents] tend to cause cytokine release syndrome in the majority of patients, mostly grades 1 or 2. Neurologic toxicity [consistently appears] in up to 20% to 25% of patients, usually low grade.

Infection is the standout toxicity that we see across the board with bispecific antibodies. If we can optimize treatments to lower those rates of infection, that will further improve outcomes for patients treated with these agents.

What is the main message you’d like to impart to colleagues regarding your research with teclistamab in patients with multiple myeloma?

The teclistamab findings were exciting in terms of response and the durability of those responses. I anticipate that with the potential upcoming approval of this drug, we will have a new therapeutic option for patients once they relapse after IMiDs, proteasome inhibitors, and anti-CD38 antibodies.

Reference

1. Krishnan A, Nooka AK, Chari A, et al. Comparative effectiveness of teclistamab versus real-world treatments for patients with triple-class exposed (TCE), relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2022;40(suppl 16):8036. doi:10.1200/JCO.2022.40.16_suppl.8036