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Phase 1 & 2 Studies Confirm Elotuzumab Enhances Effectiveness Of Revlimid & Possibly Velcade

Home/Phase 1 & 2 Studies Confirm Elotuzumab Enhances Effectiveness Of Revlimid & Possibly Velcade

Phase 1 & 2 Studies Confirm Elotuzumab Enhances Effectiveness Of Revlimid & Possibly Velcade

Elotuzumab is one of the promising new combo drugs being studied to enhance the effectiveness of Revlimid and Velcade.  I have reported on elotuzumab before.  Here is a link to a story I did about the drug following last year’s ASH meetings in New Orleans.  I then another story about elotuzumab in April.  The Myeloma Beacon did a story about elotuzumab last June.  In November, Dr. Keith Stewart with Mayo Clinic, Scottsdale, mentioned it in an interview about clinical study options for relapsed multiple myeloma patients, saying “Monoclonal antibodies which specifically target myeloma cell or interfere with the growth of myeloma cells: Elotuzumab, particularly in combination with Revlimid-dex has shown encouraging results in early studies.”

M.D. Anderson’s Dr. Robert Orlowski spoke encouragingly about elotuzumab last Friday during his IMF presentation as well, commenting how “Elotuzumab, when combined with Revlimid and dex, features a response rate of over 80% among relapsed patients.”

Here are the latest Elotuzumab updates from this year’s ASH:

December 07, 2010
Encouraging Phase 2 Interim Data for Elotuzumab in Relapsed Multiple Myeloma Presented at 52nd American Society of Hematology Annual Meeting


•Phase 2 Interim Data Show High Objective Response Rate for Patients Treated with Elotuzumab plus Lenalidomide and Low-Dose Dexamethasone
•Phase 3 Clinical Development Program to Start in Early 2011


ABBOTT PARK, Ill. & PRINCETON, N.J.–(BUSINESS WIRE)–Abbott and Bristol-Myers Squibb Company today announced interim results from the Phase 2 portion of a Phase 1b/2 open-label study which showed a high objective response rate (ORR) among patients with relapsed multiple myeloma who received elotuzumab plus lenalidomide and low-dose dexamethasone. ORR, the primary endpoint of the Phase 2 portion of the study, was defined as partial response or better and assessed using International Myeloma Working Group (IMWG) criteria. These results were presented today during an oral session at the 52nd Annual Meeting of the American Society of Hematology in Orlando.

“The preliminary Phase 2 data presented today support further investigation of the potential role of elotuzumab in combination with lenalidomide and low-dose dexamethasone as a treatment option for patients with relapsed multiple myeloma.”


Of 31 previously-treated patients who received elotuzumab 10 mg/kg plus lenalidomide and low-dose dexamethasone, 28 (90%) achieved an objective response. Of 32 previously-treated patients who received elotuzumab 20 mg/kg plus lenalidomide and low-dose dexamethasone, 23 (72%) achieved an objective response. The median time to progression-free survival was not reached after 4.9 months of follow-up.

In the study, grade 3 and 4 adverse events included neutropenia (14%), lymphopenia (14%) and thrombocytopenia (13%). The overall rate of treatment-emergent grade 3/4 adverse events was 56%. The overall rate of grade 3/4 elotuzumab-related adverse events was 24%. Of patients with infusion-related reactions, one patient (1.6%) experienced grade 3 rash within 24 hours of treatment with elotuzumab. There were no grade 4 infusion-related adverse events. The most common elotuzumab-related adverse events were fatigue (21%), pyrexia (14%), lymphopenia (11%), nausea (11%) diarrhea (11%), constipation (10%) and neutropenia (10%).

Multiple myeloma is the second most common blood cancer in the United States, with a 5-year survival rate of approximately 35%. Elotuzumab is an investigational humanized monoclonal antibody specifically directed against CS1, a cell-surface glycoprotein that is highly and uniformly present on multiple myeloma cells.

“There remains a need for more effective and tolerable treatment options for patients with relapsed multiple myeloma, as almost all patients eventually relapse and require further therapy,” said Paul G. Richardson, M.D. Clinical Director, Jerome Lipper Center for Multiple Myeloma, Dana-Farber Cancer Institute, lead author and investigator on the study. “The preliminary Phase 2 data presented today support further investigation of the potential role of elotuzumab in combination with lenalidomide and low-dose dexamethasone as a treatment option for patients with relapsed multiple myeloma.”

A Phase 3 clinical development program for elotuzumab in relapsed multiple myeloma is expected to be initiated in early 2011.

About the Phase 1b/2 Study
The primary endpoint of the Phase 2 portion of this Phase 1b/2, multicenter, open-label dose-escalation study was ORR according to the IMWG response criteria. Patients were randomized 1:1 to receive elotuzumab either 10 or 20 mg/kg (IV infusion on days 1, 8, 15, and 22 of a 28-day cycle in the first 2 cycles and then days 1 and 15 of subsequent cycles), along with lenalidomide 25 mg PO daily on days 1 to 21 and dexamethasone 40 mg PO weekly. Patients were treated until disease progression or unacceptable toxicity, if earlier. To control potential infusion reactions, patients received methylprednisolone (50 mg IV), diphenhydramine (25–50 mg PO or IV) or equivalent, ranitidine (50 mg IV) or equivalent, and acetaminophen (650–1000 mg PO) 30 to 60 minutes prior to each elotuzumab infusion.

Updated Results from a Second Phase 1b Study also Presented
Updated results from an ongoing Phase 1b study of elotuzumab in combination with bortezomib were also presented at the ASH annual meeting. In this study of elotuzumab plus bortezomib in 27 evaluable patients, 13 patients (48%) had an objective response and 17 patients (63%) achieved a clinical response, defined as minimal response or better using the combined European Group for Blood and Marrow Transplant (EBMT) criteria. Median time to disease progression was 9.46 months in the evaluable population. No dose-limiting toxicities were reported and a maximum tolerated dose was not established. The most frequent elotuzumab-related grade 3/4 AEs were fatigue and thrombocytopenia (7%). Serious adverse events related to elotuzumab included one grade 3 chest pain and one grade 3 gastroenteritis. Twenty patients (71%) experienced one or more infusion reactions. The primary endpoint for this study was the incidence of dose-limiting toxicities in the first treatment cycle for each cohort.

Encouraging news about what will hopefully become another weapon in our anti-myeloma arsenal.

Feel good and keep smiling!  Pat