Elotuzumab + Lenalidomide for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Lenalidomide

Disqualifiers: Major surgery, Radiotherapy, CNS involvement, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 5

Duration: 28 days per course, repeated until disease progression or unacceptable toxicity

113 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well elotuzumab works when given with lenalidomide as maintenance therapy after transplant in patients with newly diagnosed multiple myeloma who underwent transplant using their own stem cells (autologous transplant). Maintenance therapy is treatment that is given to help keep cancer from coming back after it has disappeared following the initial treatment. Immunotherapy with monoclonal antibodies, such as elotuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Adding elotuzumab to standard maintenance therapy with lenalidomide may work better in treating patients with multiple myeloma who have undergone transplant.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer.

What data supports the effectiveness of the drug combination Elotuzumab and Lenalidomide for treating multiple myeloma?

Research shows that the drug combination of Elotuzumab and Lenalidomide, along with dexamethasone, significantly improved the time patients lived without their disease getting worse and increased the overall response rate compared to using Lenalidomide and dexamethasone alone. This combination was approved by the FDA based on these positive results. ^{1 2 3 4 5}

Is the combination of Elotuzumab and Lenalidomide safe for treating multiple myeloma?

The combination of Elotuzumab (Empliciti) and Lenalidomide (Revlimid) for multiple myeloma has been shown to have a generally manageable safety profile, but serious side effects can occur, including infusion reactions, infections, and blood-related issues like anemia and neutropenia (low white blood cell count). It's important to monitor for these side effects and manage them appropriately during treatment. ^{1 3 6 7 8}

How does the drug Elotuzumab + Lenalidomide differ from other treatments for multiple myeloma?

Elotuzumab + Lenalidomide is unique because it combines a monoclonal antibody, elotuzumab, which targets a specific protein (SLAMF7) on myeloma and natural killer cells, with lenalidomide, enhancing the immune system's ability to attack cancer cells. This combination has shown to significantly improve progression-free survival and overall response rates in patients with relapsed or refractory multiple myeloma compared to lenalidomide and dexamethasone alone. ^{1 5 9 10 11}

Research Team

Sheeba Thomas, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with newly diagnosed multiple myeloma who have had a stem cell transplant using their own cells. Participants should be relatively healthy (ECOG status 0-2), able to follow contraception guidelines or abstain from sex, and must start the therapy within a certain time frame after transplant. They can't join if they've had major surgery or radiation recently, active hepatitis, infections needing IV antibiotics, allergies to study drugs, CNS involvement, trouble swallowing pills, are pregnant/lactating, or haven't recovered from previous treatments.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I changed my primary cancer treatment due to poor response or side effects, but haven't tried more than 2 treatments before stem cell transplant.

I had a stem cell transplant within 18 months after starting treatment for newly diagnosed myeloma.

Exclusion Criteria

My cancer has spread to my brain or spinal cord.

I have active hepatitis B or C.

I still have mild or no side effects from my last chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elotuzumab IV and lenalidomide PO as maintenance therapy post autologous stem cell transplant

28 days per course, repeated until disease progression or unacceptable toxicity

4 visits (in-person) during courses 1-2, 1 visit (in-person) for subsequent courses

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Long-term follow-up

Participants are monitored for progression free survival and overall survival

Up to 48 months

Treatment Details

Interventions

• Elotuzumab
• Lenalidomide

Trial Overview The trial tests elotuzumab combined with lenalidomide as maintenance therapy post-autologous stem cell transplant in treating multiple myeloma. The goal is to see if this combination helps prevent cancer recurrence by enhancing the immune system's response and inhibiting cancer growth compared to standard treatment.

Participant Groups

Group I: Treatment (elotuzumab, lenalidomide) Experimental Treatment 3 Interventions

Patients receive elotuzumab IV over 2-4 hours on days 1, 8, 15, and 21 of courses 1-2 and on day 1 of each subsequent course. Patients also receive lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In the phase III ELOQUENT-2 trial involving adults with relapsed multiple myeloma, elotuzumab combined with lenalidomide and dexamethasone significantly improved progression-free survival and overall response rates compared to the standard treatment alone.

The addition of elotuzumab did not negatively affect health-related quality of life and had a manageable safety profile, with the most common serious side effects being blood-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Lamb, YN.[2019]

In a phase II study involving 15 patients with relapsed multiple myeloma, the combination of elotuzumab with carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) showed a 46.7% rate of achieving very good partial response (≥VGPR) after 4 cycles of treatment, indicating significant efficacy in a challenging patient population.

The treatment was well-tolerated with no new safety concerns reported, and the overall response rate was 80%, suggesting that Elo-KRd is a promising option for patients with high-risk and lenalidomide-refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse. Bhutani, M., Foureau, DM., Robinson, M., et al.[2023]

Elotuzumab, when combined with lenalidomide and dexamethasone, significantly improves progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma, with a median PFS of 19.4 months compared to 14.9 months for the standard treatment.

The treatment showed a higher overall response rate (ORR) of 75.8% versus 65.5% for the standard therapy, although serious adverse reactions were more common in the elotuzumab group (65% vs. 57%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. Gormley, NJ., Ko, CW., Deisseroth, A., et al.[2018]

In a study of 117 patients with relapsed or refractory multiple myeloma, those treated with elotuzumab plus pomalidomide and dexamethasone experienced a median progression-free survival of 10.3 months, compared to 4.7 months for those receiving pomalidomide and dexamethasone alone, indicating a significant improvement in treatment efficacy.

The overall response rate was also higher in the elotuzumab group at 53% versus 26% in the control group, with fewer severe adverse events like neutropenia and anemia, suggesting that elotuzumab may enhance treatment outcomes while maintaining a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2019]

Elotuzumab, a monoclonal antibody targeting the SLAMF7 receptor, shows significant antimyeloma activity when combined with other treatments like bortezomib or lenalidomide, improving patient responses without adding extra toxicity.

Approved by the FDA in 2015 for patients with relapsed or refractory multiple myeloma after 1-3 prior therapies, elotuzumab has demonstrated efficacy in clinical trials, particularly in combination therapies, while showing a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of elotuzumab for the treatment of multiple myeloma. Gavriatopoulou, M., Terpos, E., Kastritis, E., et al.[2018]

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 the phase II ELOQUENT-3 trial, the combination of elotuzumab with pomalidomide and dexamethasone (EPd) significantly improved overall survival (OS) in patients with relapsed/refractory multiple myeloma, with a median OS of 29.8 months compared to 17.4 months for the pomalidomide/dexamethasone (Pd) group.

The safety profile of EPd was consistent with previous studies, showing no new safety concerns, indicating that this treatment is both effective and safe for patients who have already undergone multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2023]

Elotuzumab, a humanized monoclonal antibody targeting SLAMF7, has been shown to enhance the effectiveness of treatments for relapsed and/or refractory multiple myeloma when combined with lenalidomide/dexamethasone or pomalidomide/dexamethasone, leading to FDA approval for these combinations.

The use of elotuzumab stimulates natural killer cells to attack multiple myeloma cells, offering a promising mechanism of action that could improve treatment outcomes without significantly increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab in the treatment of relapsed and refractory multiple myeloma. Grosicki, S., Bednarczyk, M., Barchnicka, A., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. [2018]

4. England pubmed.ncbi.nlm.nih.gov

A review discussing elotuzumab and its use in the second-line plus treatment of multiple myeloma. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 3-year follow-up of a multicenter, retrospective clinical experience with 319 cases outside of controlled clinical trials. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of elotuzumab for the treatment of multiple myeloma. [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Elotuzumab: First Global Approval. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Elotuzumab in the treatment of relapsed and refractory multiple myeloma. [2021]