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Elotuzumab Combination Is Effective For Relapsed Myeloma (ASCO 2011)

5 Comments By and
Published: Jun 10, 2011 2:01 pm

Results of a Phase 2 clin­i­cal trial show that elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone is safe and ef­fec­tive in re­lapsed / refractory mul­ti­ple myeloma patients.

“Elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone has a very high re­sponse rate,” said Dr. Philippe Moreau from the Uni­ver­sity Hospital in Nantes, France, when he pre­sented the findings at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) on Sunday.

“[The com­bi­na­tion] seems to be superior to Revlimid plus high-dose dexa­meth­a­sone,” he added.

In a summary talk about po­ten­tial new myeloma treat­ments, Dr. Nikhil Munshi from the Dana-Farber Cancer In­sti­tute was enthusiastic about the study re­­sults. “Elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone appears to be very promising,” he said.

He pointed out that it would be in­ter­est­ing to see if this drug also has single-agent ac­­tiv­ity.

Elotuzumab is a drug under de­vel­op­ment by Bristol-Myers Squibb that identifies pro­teins on the surface of myeloma cells and incites the im­mune sys­tem to destroy the cancer cells.

Results of the preceding Phase 1 study showed that 82 per­cent of re­lapsed / refractory myeloma patients responded to elotuzumab in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron).

Interim re­­sults of both the Phase 1 and Phase 2 trials were pre­sented at the American Society of He­ma­tol­ogy annual meeting last De­cem­ber (see re­lated Beacon news).

The ran­dom­ized Phase 2 study en­rolled 98 re­lapsed / refractory myeloma patients with a median age of 62 years. Patients had re­ceived a median of two prior ther­a­pies. Two-thirds of patients had prior Velcade (bor­tez­o­mib) ther­apy, and 60 per­cent had prior thalidomide (Thalomid) ther­apy, while patients who were pre­vi­ously treated with Revlimid were excluded from the study.

Half of the patients re­ceived 10 mg/kg in­tra­venous elotuzumab, and the other half re­ceived 20 mg/kg. Patients re­ceived elotuzumab on days 1, 8, 15, and 22 of the first two 28-day cycles and on days 1 and 15 of sub­se­quent cycles.

In addi­tion, they re­ceived 25 mg oral Revlimid on days 1 to 21, along with 40 mg low-dose dexa­meth­a­sone once per week.

The patients were also given anti-in­flam­ma­tory drugs prior to elotuzumab in order to prevent the elotuzumab-related in­fusion reac­tions observed in the Phase 1 trial.

Patients con­tinued to re­ceive treat­ment until their dis­ease progressed or until they ex­peri­enced severe side effects.

The study authors found that 82 per­cent of patients responded to treat­ment, with 9 per­cent of patients achieving a com­plete re­sponse, 33 per­cent a very good partial re­sponse, and 40 per­cent a partial re­sponse.

However, the re­sponse rate was higher for the 10 mg/kg group than the 20 mg/kg group (92 per­cent versus 75 per­cent. Based on these findings, Dr. Moreau and his colleagues rec­om­mended the 10 mg dose for the Phase 3 trial.

Additionally, among patients who had re­ceived one prior ther­apy, the over­all re­sponse rate was 90 per­cent. “This [finding] provides the rationale for investigating this com­bi­na­tion earlier in the course of the dis­ease, as part of a front-line treat­ment,” he ex­plained.

The median time to re­sponse was 30 days, which Dr. Moreau described as short.  

With a median follow-up of nine months, the median pro­gres­sion-free sur­vival has not been reached yet.

According to Dr. Moreau, the treat­ment was well tol­er­ated. The most common severe side effects in­cluded low white blood cell counts (20 per­cent), low platelet counts (17 per­cent), and low red blood cell counts (10 per­cent).

“The main side effects are re­lated to the Revlimid use,” ex­plained Dr. Moreau.

Elotuzumab-related side effects in­cluded nausea (16 per­cent), dizzi­ness (13 per­cent), and fever (10 per­cent).

Thirty-nine per­cent of patients stopped treat­ment, mainly due to dis­ease pro­gres­sion or side effects.

For more in­for­ma­tion, see abstract 8014 on the ASCO meeting website.

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5 Comments »

  • Gary said:

    Howard/Julie: Fantastic job of summarizing this work. As usual I find your review much easier to understand then the abstract of the paper since it captures the issues important to us patients in a language we can understand.

    Based on the results reported I worry that we may be producing another treatment agent for which we do not know the optimal dosage regimen. Dr. Moreau seems willing to select 10 mg levels of elotuzumab over 20mg for revlamid Levels of 25 mg and "low dose" dex of 40 mg. How about 15 mg or even 5 mg? How about elotuzumab levels from 5mg to 20mg at different levels of revlamid and dex? Surely,it is important to determine the synergies of elotuzumab with revlamid and dex? Not knowing this information got us in trouble overdosing with Velcade and dex.

    I don't mean to shoot the messenger. I assume that one or more of the coauthors including Bristol Myers Squibb blessed your summary of the work. I would very much appreciate your sharing my concerns with them and ask if they would be willing to discuss the important issue of personalizing the dose to the individual patient.

    I really want these new agents. I just want them to be at levels and frequencies that have the best chance of reducing our MM with minimum side effects.

    Thank you again for your good work.
    Gary

  • Julie Shilane (author) said:

    Hi Gary,

    Thanks for your kind words about our work.

    Here are a few more details about this combination and the rationale behind the doses tested:

    In the Phase 1 study of this combination, elotuzumab was tested at 5 mg/kg (3 patients), 10 mg/kg (3 patients), and 20 mg/kg (22 patients). Based on a chart in the poster for this study, the response rates for the different doses are approximately the following:
    5 mg/kg: 100% ORR (100% PR)
    10 mg/kg: 100% ORR (33% VGPR, 66% PR)
    20 mg/kg: 78% ORR (5% CR, 50% VGPR, 23% PR)
    ORR = overall response rate
    PR = partial response
    VGPR = very good partial response
    CR = complete response

    Because the overall response rate was the same for the 5 and 10 mg/kg dosing, but the type of response was better for the 10 mg/kg dosing, the Phase 2 study further investigated the 10 and 20 mg/kg doses of elotuzumab.

    With these combination studies, researchers generally try to administer the already approved and proven effective treatments at full dose and see whether the new drug improves the efficacy of the standard regimen. They often only vary the dose of the new drug (not the already approved drugs) to see what dose is most effective and well tolerated.

    There certainly are many more combinations of doses that would be feasible, and possibly a bit better (efficacy and safety-wise). However, it is difficult to test all of those possibilities in people. It can be difficult to enroll enough patients to determine which is the best of many options, and it certainly would add to the cost of clinical trials to have to enroll significantly more patients.

    Even if more combinations of doses were tested, I'm not sure how that would help personalize the dose to the individual patient. As I'm sure you well know, each individual does not necessarily respond the same way as the majority of the group.

    Finally, although we do reach out to study authors to get comments or answers to questions related to studies we cover here at the Beacon, none of our articles are subject to approval by either the study authors or study sponsors. We know that our independence and objectivity are valuable to our readers.

  • Gary said:

    Julie: Thank you for the added information. As I feared the dose is not optimized against the other treatment combinations. If a pharmaocometric study is not in conducted by the drug manufacturers than you are correct it is virtually impossible to enroll sufficient patients using randomized clinical trials to find the best dose for an individual. But pharmacometric studies can and should be conducted by Bristol-Myers Squibb. By knowing the uptake,distribution and elimination of elotuzumab in a population of patients (the population model) and correlating these results with the pharmacogenomics, efficacy and side effects for different values of dex/revlamid it would provide the information needed to optimize the dose for an individual.
    Here is how it would work. The patient would need to be administered a cocktail of low levels of dex,revlamid and elotuzumab BEFORE chronic administration. One or two blood samples would drawn a few hours after this administration and the behavior of the drug combination in the actual patient determined. This information would them be used to determine the unique dose regimen for the INDIVIDUAL from the population model. Then the chronic dosing could be started probably the next day. How simple.
    However, it costs a little more upfront but could be so beneficial to us patients. We need to convince BMS to get this data and release it to the clinical oncologists.

  • Jane said:

    My husband has relapsed MM and we would like to receive this new drug. Are there any studies presently (6-11)using this new drug? Where? How can I contact someone about this? Thanks, Jane

  • Myeloma Beacon Staff said:

    Hi Jane,

    There are several ongoing elotuzumab studies. You may be particularly interested in a Phase 3 international study recruiting patients with relapsed/refractory multiple myeloma. All participants will receive Revlimid plus dexamethasone, and half will also receive elotuzumab. You can find more information in the clinical trial description. Your husband's physician should be able to help your husband determine whether he is eligible for the trial and, if so, put you in contact with the study investigators. If his physician is unable to help, the link provided above includes a list of all of the participating treatment centers and a contact name and phone number for the centers that are recruiting at this time.