Long-Term Depth of Response With Teclistamab Continues in RRMM

CASE SUMMARY

• A 63-year-old man was diagnosed 8 years ago with multiple myeloma (IgG-kappa)​
• He lives in a rural community.​
• He now presents with penta-refractory disease progression.
• Completed 4 prior lines of therapy, which included autologous stem cell transplant, 2 proteasome inhibitors, 2 immunomodulatory drugs, and 1 anti-CD38 antibody​.

Medical History​

• Hypertension controlled with lisinopril​.
• ECOG performance status: 1

Targeted Oncology^TM: What was the design of the trial that led to the approval of teclistamab (Tecvayli) for patients with relapsed/refractory multiple myeloma (RRMM)?

NOOKA: The MajesTEC-1 trial [NCT03145181; NCT04557098], which is a phase 1/2 trial...led to the accelerated approval of teclistamab.¹ MajesTEC-1 had 2 cohorts that were evaluated. The first cohort was given teclistamab intravenously [IV] and the second cohort [was given teclistamab] subcutaneously.²

Ajay Nooka, MD, MPH

Director, Myeloma Program

Department of Hematology and Medical Oncology

Scientific Director

Winship Data and Technology Applications Shared Resource

Winship Cancer Institute​

Emory University School of Medicine​

In the earlier days, most of the bispecific antibodies were developed [to be given IV, but recent data] have been transformative with the subcutaneous cohorts as we learned that they could be much better tolerated [this way], and this [is an easier method] to administer these drugs. So, patients who had a good performance status, were triple class exposed, and who did not receive any prior B-cell maturation agent [BCMA]-targeted therapy were enrolled into the earlier phase 1 trial, and [then escalated to the phase 2] cohort A with 1.5 mg/kg of teclistamab given subcutaneously weekly.²

What were the end points and baseline patient characteristics of this study?

The overall response rate [ORR] was a primary end point, and there were several other secondary end points including the pharmacokinetics and pharmacodynamics, progression-free survival [PFS], duration of response [DOR], and minimal residual disease [MRD] negativity.³ It is exciting to speak about MRD negativity, even in this heavily refractory space, because [before these bispecific agents] we were getting [much lower complete response (CR) rates], which is always an example that I give to show where we started and where we are now—seeing much better depths of responses, even among these heavily pretreated patients who had seen 6 months of therapy.

[On the MajesTEC-1 trial], there was a younger population of patients at a median age of 64 years old...but around 15% of the patients were age 75 years or older. They were all triple class exposed, and [77.6% of enrolled patients were] triple class refractory, [30.3% were] penta-refractory, and the median prior lines of therapy was 5 [range, 2-14]. Moreover, these were the patients who had seen a median of 6 years from the time of their diagnosis. After you cross 3 or 4 lines of therapy, the way I see it is that every patient’s disease behaves like high-risk disease, and this is a heavily pretreated patient population who are refractory to the last line of therapy.³

What were the initial efficacy results in MajecTEC-1 for patients with RRMM?

In these patients, we saw an ORR of 63%...and [58.8%] of these responses were very good partial responses [VGPR]. Between stringent CRs and CRs, there was a rate of 39.4%. So, these are deep responses...and they are durable with 104 of the 165 patients responding...at a median DOR of more than a year and half. The median PFS was [11.3] months and the median overall survival [OS] was 18.3 months.... That survival benefit was seen across all subtypes of patients including patients with renal failure, patients with extra medullary disease, patients who have high-risk disease, and patients who have standard-risk disease. Every subgroup has benefited from the usage of teclistamab.

How does the updated safety and efficacy data from the 2023 American Society for Clinical Oncology Annual Meeting change considerations with this therapy?

At a median follow-up of about 22 months, high-risk cytogenetics were seen in a third of the patients.⁴ The median PFS extended beyond that initial 11.3 months to 12.5 months and the median OS at this data cut off was reaching beyond that initial 18 months to 21.9 months. For this long-term follow-up, [grade 3 or 4] neutropenia [65%], anemia [38%], and thrombocytopenia [22%] were seen as major hematological toxicities while lymphopenia was seen in a third of these patients. When you're seeing this lymphopenia, it is the patients that are at risk for opportunistic infections and are the high-risk patient population for infection rates.

We have never used these drugs in the past and are seeing that the T-cell redirection and T-cell depletion, which you tend to see in this patient population post allogenic transplant; also the viral reactivations that you see when people don't have functional T cells is what we are seeing as adverse events [AEs] with these drugs. It is good for us to understand these AEs, so that we can act on them and make sure that the patients get the right prophylaxis, the toxicities are minimized, and they still get the benefit of [this drug class].

^References

^{1. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. Press Release. October 25, 2022. Accessed, August 25, 2023. https://tinyurl.com/mrxhrw3c}

^{2. Usmani SZ, Karlin L, Benboubker L, et al. Durability of responses with biweekly dosing of teclistamab in patients with relapsed/refractory multiple myeloma achieving a clinical response in the majesTEC-1 study. J Clin Oncol. 2023;41(6):8034. doi:10.1200/JCO.2023.41.16_suppl.8034}

^{3. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi:10.1056/NEJMoa2203478}

^{4. van de Donk NWCJ, Moreau P, Garfall A, et al. Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(6):8011. doi:10.1200/JCO.2023.41.16_suppl.8011}