Elotuzumab Combination Is Effective For Relapsed Myeloma (ASCO 2011)
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.
Related Articles:
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- bb2121 Continues To Impress As Potential New Multiple Myeloma Therapy (ASCO 2018)
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Lather, Rinse, Repeat: Will It Work With BCMA-Targeted Therapies For Multiple Myeloma?
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
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.
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.
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
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.
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