Elotuzumab with high-risk myeloma
Photo: tyfn/flickr CC
A Randomized Phase I/II Study of Optimal Induction Therapy of Bortezomib, Dexamethasone and Lenalidomide With or Without Elotuzumab (NSC-764479) For Newly Diagnosed High Risk Multiple Myeloma (HRMM)
Though therapeutic advances have improved survival times for multiple myeloma (MM) patients generally, those with high-risk MM still face a poor prognosis, and no clinical investigations have specifically targeted this population. SWOG study S1211 has been designed to address this need for new treatment regimens that may improve outcomes for high-risk patients.
The investigative agent being assessed is elotuzumab (Elo), a monoclonal antibody that acts against the CS1 cell surface protein, which is expressed in much higher levels on MM cells than on normal cells.
"Elo has returned promising results in in vitro tests in human MM cells and in in vivo tests in mice," says Saad Z. Usmani, M.D., of the University of Arkansas for Medical Sciences, lead study coordinator for S1211. "It has also shown considerable promise in early clinical trials."
Elo and RVD
In S1211, Elo will be given with an induction regimen of lenalidomide, bortezomib, and dexamethasone (RVD). The phase I portion of the trial will determine the maximum tolerated dose (MTD) of Elo to use with this combination.
The phase II portion will randomly assign patients to RVD with elotuzumab or RVD alone, and will assess whether adding Elo to RVD improves progression-free survival (PFS) for high-risk MM patients. Patients will be stratified according to the presence of primary plasma cell leukemia (PPCL) and/or LDH.
Who is high-risk?
"High-risk" in S1211 is defined in keeping with the guidelines agreed on by the NCI Myeloma Steering Committee in 2011, meaning patients with at least one of the following:
- MyPRS 70-gene poor risk score
- FISH or cytogenetics showing translocation (14;16) or (14;20) or deletion (17p)
- primary plasma cell leukemia (PPCL)
- elevated serum lactate dehydrogenase (LDH)
Patients with newly diagnosed, measurable multiple myeloma who have adequate marrow, hepatic, and renal function, no active involvement of the central nervous system, and no other clinically significant illness (e.g., no diabetes or hypertension) may be eligible. For the phase I portion, both standard-risk and high-risk patients can participate. For the phase II portion, patients must also meet one or more of the high-risk criteria above.
Phase I of the trial is expected to open later this fall, but materials will be posted to the SWOG website in late September so phase I sites can start the review process with their local IRB.
Participation in this first phase of the trial is limited to about two dozen selected institutions, but phase II will be open to all SWOG member, CCOP, and affiliate sites. The phase II accrual target is 110 patients.