Teclistamab + Lenalidomide for Multiple Myeloma

(MajesTEC-4 Trial)

Recruiting at 286 trial locations

Overseen By Sabrin Tahri

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stichting European Myeloma Network

Must not be taking: BCMA-directed, Immune cell redirecting

Disqualifiers: Prior BCMA therapy, Gene therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 8 years

1594 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new combination of treatments—teclistamab (a type of immunotherapy) with lenalidomide, and teclistamab alone—can help people with newly diagnosed multiple myeloma more effectively than lenalidomide alone. Multiple myeloma is a type of blood cancer that affects bone marrow. The trial targets those recently diagnosed with this condition who have already undergone a stem cell transplant and have not yet started maintenance therapy. Participants should have responded positively to their initial treatment without experiencing a worsening of their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must not have received any maintenance therapy before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using teclistamab and lenalidomide together is generally safe for patients with newly diagnosed multiple myeloma as a maintenance therapy. Studies have found that teclistamab, whether used alone or with lenalidomide, is usually safe. Most patients can manage these treatments after undergoing a stem cell transplant.

In studies involving teclistamab, some patients experienced infections, and a significant number of these were serious. However, many patients still responded well to the treatment, suggesting that the benefits might outweigh the risks for some individuals.

Lenalidomide, already approved for treating multiple myeloma, commonly causes side effects like tiredness and low blood counts. These side effects are usually manageable with medical care.

Overall, while both treatments carry some risks, they have been shown to be safe enough for clinical trials. Always consult a healthcare provider to understand what these findings mean personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about teclistamab and lenalidomide for multiple myeloma because these treatments offer unique approaches compared to standard therapies like proteasome inhibitors and immunomodulatory drugs. Teclistamab is distinctive as it targets BCMA (B-cell maturation antigen) on myeloma cells, potentially offering a more direct attack on cancer cells. It is administered via subcutaneous injection, which might be more convenient and tolerable for patients compared to traditional intravenous methods. Lenalidomide, when used alone, remains a potent oral therapy that modulates the immune system to fight cancer, but in combination with teclistamab, it could enhance the overall anti-cancer effect. This combination and the innovative mechanism of action of teclistamab are what make this trial particularly promising.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will compare different treatment approaches for multiple myeloma. Studies have shown that teclistamab, both alone and combined with lenalidomide, holds strong potential for treating multiple myeloma. Participants may receive teclistamab alone, which demonstrated a 63% overall response rate in patients whose multiple myeloma returned or did not respond to other treatments. Alternatively, some participants will receive a combination of teclistamab and lenalidomide, which led to significant improvements, with some achieving minimal residual disease (MRD) negativity, meaning no cancer cells were detectable. These findings suggest that teclistamab, whether used alone or with lenalidomide, could be a powerful option for treating multiple myeloma. ^{1 6 7 8 9}

Who Is on the Research Team?

Niels van de Donk, Professor

Principal Investigator

Amsterdam UMC, Vrije Universiteit Amsterdam

Elena Zamagni, Professor

Principal Investigator

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli"

Are You a Good Fit for This Trial?

This trial is for individuals newly diagnosed with multiple myeloma who have had only one line of therapy and achieved at least a partial response. They must not have received maintenance therapy, should be relatively fit (ECOG score 0-2), and their lab values need to be within certain limits. People intolerant to lenalidomide or those who've had previous maintenance treatments can't participate.

Inclusion Criteria

Have clinical laboratory values within prespecified range.

I have not received any maintenance therapy.

I can care for myself and am up and about more than 50% of my waking hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance therapy with teclistamab in combination with lenalidomide, teclistamab alone, or lenalidomide alone following autologous stem cell transplantation

up to 8 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Teclistamab

Trial Overview The study compares the effectiveness of teclistamab combined with lenalidomide and teclistamab alone against just lenalidomide as post-autologous stem cell transplant maintenance therapy in new multiple myeloma patients. It's a Phase 3 trial where participants are randomly assigned to these treatment groups.

How Is the Trial Designed?

Group I: Arm C Teclistamab-Alone (Tec) Experimental Treatment 1 Intervention

Teclistamab will be administered via a subcutaneous injection (SC)

Group II: Arm A: Teclistamab-Lenalidomide (Tec-Len) Experimental Treatment 2 Interventions

Teclistamab will be administered via a subcutaneous injection (SC)

Group III: Arm B Lenalidomide Alone (Len) Active Control 1 Intervention

Lenalidomide orally.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Stichting European Myeloma Network

Lead Sponsor

Trials

28

Recruited

18,600+

European Myeloma Network

Lead Sponsor

Trials

27

Recruited

12,600+

Janssen Pharmaceutica

Industry Sponsor

Trials

43

Recruited

9,200+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Immunology Treatments

Top Products

Stelara (ustekinumab), Darzalex (daratumumab), Remicade (infliximab), Tremfya (guselkumab)

Published Research Related to This Trial

Lenalidomide (Revlimid) has been rapidly developed and recently approved for treating relapsed multiple myeloma, showing durable clinical responses, especially when combined with dexamethasone.

Clinical trials indicate that lenalidomide is generally well tolerated by patients, with manageable side effects, making it a promising option for those with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. Richardson, PG., Mitsiades, C., Hideshima, T., et al.[2018]

Immunomodulatory drugs like thalidomide and lenalidomide have shown significant effectiveness in treating multiple myeloma and related blood disorders, demonstrating high response rates across various treatment phases.

These drugs not only target cancer cells directly but also enhance the immune response within the bone marrow, and have been successfully combined with other treatments, leading to FDA approval for their use in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma. Raje, N., Hideshima, T., Anderson, KC.[2018]

Lenalidomide has become a crucial treatment option for multiple myeloma and del-5q myelodysplastic syndromes, and it has been tested for various other cancers, showcasing its broad therapeutic potential.

The drug received FDA approval for use in combination with dexamethasone for previously treated multiple myeloma, highlighting its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. Galustian, C., Dalgleish, A.[2019]

Lenalidomide, a derivative of thalidomide, has improved potency and a better side-effect profile, particularly with reduced neurologic toxicity compared to its predecessor.

While lenalidomide shows promise in treating conditions like myelodysplastic syndrome and multiple myeloma, there are still concerns about pro-thrombotic effects, especially when used with dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. Crane, E., List, A.[2018]

Lenalidomide significantly improves progression-free survival (PFS) in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation, as shown in randomized trials like the FIRST and MM-015 trials.

Continuous lenalidomide therapy is associated with less toxicity compared to thalidomide, maintaining tolerability without increasing the risk of neutropenia or second primary malignancies, making it a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. McCormack, PL.[2018]

A subgroup analysis from two phase III clinical trials demonstrated that combining lenalidomide with dexamethasone is more effective than using dexamethasone alone for patients with relapsed or refractory multiple myeloma who had prior treatment with thalidomide.

This finding suggests that the lenalidomide and dexamethasone combination could be a more beneficial treatment option for these patients, potentially improving their outcomes in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. Meijer, E., Sonneveld, P.[2021]

Lenalidomide, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

Lenalidomide has shown significant efficacy in improving survival rates for patients with relapsed and refractory myeloma, especially when used alongside other treatments like bortezomib and thalidomide.

While lenalidomide is effective, it is associated with common side effects such as fatigue and thrombocytopenia, and its combination with other agents can increase the risk of blood clots, highlighting the importance of managing these adverse events for continued treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. van de Donk, NW., Görgün, G., Groen, RW., et al.[2021]

In a phase 3 trial involving 301 transplant-ineligible patients with newly diagnosed multiple myeloma, the combination of pembrolizumab with lenalidomide and dexamethasone did not show a significant improvement in progression-free survival compared to lenalidomide and dexamethasone alone, with 6-month estimates of 82.0% vs 85.0%.

The addition of pembrolizumab was associated with a higher rate of serious adverse events (54% vs 39%) and treatment-related deaths (4% vs 1%), leading to an unfavorable benefit-risk profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Usmani, SZ., Schjesvold, F., Oriol, A., et al.[2019]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

Lenalidomide is an effective treatment for patients with relapsed or refractory multiple myeloma, showing promising clinical activity and is approved by the FDA.

Common side effects of lenalidomide include neutropenia, thrombocytopenia, and thromboembolic events, necessitating careful monitoring to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. Tariman, JD.[2018]

Citations

1. nature.com nature.com/articles/s41408-025-01314-9

Outcomes of teclistamab in patients with relapsed/ ... Treatment with SOC teclistamab yielded an ORR of 48.7% in the prior BCMA-DT group, which compares favorably with the ORR of 52.5% reported in ...

2. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/real-world-data-shows-teclistamab-can-benefit-many-multiple-myeloma-patients-who-would-have-been-ineligible-for-pivotal-trial/

Real-world Data Shows Teclistamab Can Benefit Many ... Real-world Data Shows Teclistamab Can Benefit Many Multiple Myeloma Patients Who Would Have Been Ineligible for Pivotal Trial. July 9, 2025 ...

3. tecvaylihcp.com tecvaylihcp.com/clinical-study-results/

Clinical Study Results | TECVAYLI® (teclistamab-cqyv) HCP The efficacy of TECVAYLI® was evaluated in 110 patients with relapsed or refractory multiple myeloma in the single-arm, open-label, multi-center, phase 1/2 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40352937/

Effectiveness and safety of teclistamab for relapsed or ... Teclistamab continues to be a promising and effective treatment option for RRMM patients, including those previously exposed to BCMA-targeted therapies.

5. ashpublications.org ashpublications.org/bloodadvances/article/9/19/4806/546235/The-efficacy-of-teclistamab-in-patients-with

The efficacy of teclistamab in patients with multiple myeloma ... Long-term follow-up results of the MajesTec trial have shown promising efficacy of teclistamab in RRMM with overall response rate (ORR) of 63% ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40744810/

Real-World Efficacy and Safety of Teclistamab for Patients ... Given the historically poor outcomes observed in patients with triple-class exposed RRMM, teclistamab treatment should be strongly considered ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2203478

Teclistamab in Relapsed or Refractory Multiple Myeloma Teclistamab resulted in a high rate of deep and durable response in patients with triple-class–exposed relapsed or refractory multiple myeloma.

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2398/532408/Dosing-Patterns-and-Early-Safety-and-Effectiveness

Dosing Patterns and Early Safety and Effectiveness Outcomes ... Dosing patterns and early safety and effectiveness outcomes in patients with multiple myeloma treated with Teclistamab in the community setting.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19504

Real-world outcomes of teclistamab for the treatment ... The incidence of infection was 67%; the majority were grade ≥ 3. The overall response rate (ORR) by IMWG criteria was 50%. All patients who ...