Treatment Options - Elotuzumab
What is Elotuzumab?
Elotuzumab, also known as HuLuc63, is a monoclonal antibody being developed by Abbott in collaboration with Bristol-Myers Squibb. Elotuzumab binds to CS1, a substance that is on the surface of myeloma cells. This agent is given as an intravenous infusion.
The Multiple Myeloma Research Consortium (MMRC) has played a role in this drug’s development and is currently facilitating several trials evaluating elotuzumab in combination with other myeloma agents.
What do we know about Elotuzumab’s activity in myeloma?
In the laboratory, elotuzumab has been shown to kill myeloma cells, including those that are resistant to other anti-myeloma therapies. When elotuzumab is combined with other anti-myeloma therapies, the activities of both are enhanced (ie, they act synergistically). Elotuzumab also caused tumor shrinkage in mice.
Elotuzumab was evaluated as part of combination therapy in two clinical trials in myeloma that were facilitated by the MMRC:
- A Phase Ib/II trial in combination with Velcade® (bortezomib) in patients with relapsed and/or refractory myeloma who received one to three prior therapies
- Final results from 27 patients in the Phase Ib portion of the study show that the combination had a manageable side effect profile.
- The overall response rate was 48%, with responses seen in patients whose disease had previously stopped responding to Velcade.
- The average time to progression of myeloma 9.5 months.
- Overall, the findings suggest that elotuzumab may enhance the effectiveness of Velcade.
- Enrollment is ongoing in the randomized Phase II portion of the study, which is evaluating Velcade-dex with and without elotuzumab.
- A Phase Ib/II trial in combination with Revlimid® (lenalidomide) and dexamethasone in patients with relapsed and/or refractory myeloma
- In the phase II portion of the study (73 patients), half of the patients received 10 mg/kg of elotuzumab, while the other half received 20 mg/kg elotuzumab, both in combination with Revlimid and dexamethasone.
- This combination had encouraging activity in patients with relapsed disease who have poor prognostic features, including cytogenetic abnormalities, stage II or III disease, and/or refractory disease. .
- For patients at the 10 mg/kg elotuzumab dose, 92% responded to treatment with a partial response or better, with 14% of patients achieving a complete response or stringent complete response and 47% achieving very good partial response.
- In patients who had received only one prior therapy, the overall response rate was 100%.
- These response rates are higher than what is expected for Revlimid and dexamethasone in the relapsed/refractory setting.
- Patients with high-risk genetic features achieved response rates that were similar to patients with standard-risk disease. However, progression-free survival was shorter in patients with high-risk disease.
- The combination was generally well tolerated.
- The most common severe side effects included low white and red blood cell counts and low platelet counts, which are effects typical of Revlimid therapy.
- Other common side effects associated with the infusion of elotuzumab included nausea, dizziness, headache, and fever. The number and severity of these reactions were reduced with use of medication prior to treatment.
How is Elotuzumab currently being studied in myeloma?
As a result of the encouraging results seen in the Phase I and II studies, elotuzumab is being evaluated in late-stage clinical trials. Two Phase III trials are evaluating whether adding elotuzumab to Revlimid-low-dose dexamethasone will increase the length of time before the disease progresses.
- The first trial (ELOQUENT-2) is being conducted in patients with relapsed or refractory myeloma and has completed enrollment.
- The second trial (ELOQUENT-1) is being conducted in patients with newly diagnosed, previously untreated myeloma and will enroll up to 750 patients.
Additional trials being conducted include:
- A Phase II study of Velcade-dex with or without elotuzumab in patients with relapsed or refractory myeloma. This study will enroll 150 patients in the US, Canada, and Europe and is being facilitated by the MMRC.
- A Phase II study in patients with high-risk smoldering myeloma that is examining whether patients who have higher numbers of specific immune cells (natural killer cells) will have better responses to elotuzumab.
- A Phase I/II study of Velcade-dex-Revlimid with or without elotuzumab in patients with newly diagnosed, high-risk myeloma.
- A Phase I study of elotuzumab in combination with Revlimid and low-dose dexamethasone in myeloma patients with various levels of kidney (renal) function. The purpose of the study is to determine the blood levels of elotuzumab in patients with very low kidney function, including patients on dialysis.