Relapsed/Refractory Patients:

Elotuzumab (HuLuc63)

What are the key facts about Elotuzumab?

• Monoclonal antibody that is given as an intravenous infusion.

• Demonstrated encouraging activity in relapsed and/or refractory myeloma when given in combination with agents such as Velcade or Revlimid-dex.

• Preliminary results from the Revlimid-dex study show an overall response rate of 82%, with encouraging activity seen in patients with relapsed disease who had poor prognostic features.

• The most common side effects seen with elotuzumab are infusion reactions. The number and severity of these reactions could be reduced with use of premedication.

• Being evaluated in combination with Revlimid-low-dose-dex in two Phase III trials. One study is in relapsed or refractory myeloma, the other is in newly diagnosed disease.

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.

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.

Single-agent Elotuzumab

Elotuzumab was evaluated in a Phase I study in patients with relapsed/refractory myeloma, where it was shown to have a manageable side effect profile.

Combination Studies

Elotuzumab was evaluated as part of combination therapy in two clinical trials in myeloma that were facilitated by the Multiple Myeloma Research Consortium (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 evaluable 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%, and activity was seen in patients whose disease had previously stopped responding to Velcade.
  
  
• The median time to disease progression was 9.46 months in the overall study group as well as in bortezomib-naïve patients.
  
  
• Overall, the findings suggest that elotuzumab enhances the activity of Velcade.
  
  
• o 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
  
• The Phase I portion of the study evaluated the maximum tolerated dose, safety, and efficacy of the combination in 28 heavily pretreated patients.
  
  
• Patients received escalating doses of 5, 10, or 20 mg/kg elotuzumab in combination with Revlimid-dex.
  
  
• Eighty-two percent of patients responded to treatment with a partial response or better.
  
  
• All doses of elotuzumab were well tolerated and the maximum tolerated dose was not reached during dose escalation.
  
  
• Infusion reactions appeared to be the main elotuzumab-related side effect seen.
  
  
• Preliminary results from the phase II portion of the study show a high overall response rate with the combination in patients who had received 1 to 3 prior therapies.
  
  
• In this study (n=73 patients enrolled to date), 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. Patients also received medication to help prevent infusion reactions.
  
  
• Eighty-two percent of patients responded to treatment with a partial response or better, with 12% of patients achieving a complete response. In patients who had received only one prior therapy, the overall response rate was 91%.
  
  
• In patients receiving 10 mg/kg of elotuzumab, the overall response rate was 92%.
  
  
• In patients receiving 20 mg/kg of elotuzumab, the overall response rate was 73%.
  
  
• These overall response rates are higher than the expected response rate for Revlimid and dexamethasone seen in the relapsed/refractory setting.
  
  
• The median time to disease progression had not been reached after 14.1 months of follow-up.
  
  
• The combination was generally well tolerated.
  
  
• The most common severe side effects included low white and 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 premedication.
  
  
• A analysis of this study showed that elotuzumab in combination with Revlimid-dex had encouraging activity in patients with relapsed disease who have poor prognostic features, including high-risk cytogenetic features, stage II or II disease (based on beta2-microglobulin level), and/or refractory disease.
  
  

How is Elotuzumab currently being studied in myeloma?

As a result of the encouraging activity 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 is being conducted in patients with relapsed or refractory myeloma and will enroll up to 640 patients.
  
  
• The second trial 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 randomized 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 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.
  
  

To find a clinical trial, call 1-866-603-MMCT (-6628) or click here to go to the MMRF Patient Navigator Program.