Elotuzumab plus stem cell transplant shows promise for multiple myeloma

SALT LAKE CITY — The addition of elotuzumab and autologous peripheral blood mononuclear cell reconstitution to autologous hematopoietic stem cell transplantation plus lenalidomide maintenance appeared effective with a manageable safety profile, according to results of a phase 1b open-label trial presented at BMT Tandem Meetings.

“The autologous HSCT platform is a good setting for exploring immunotherapeutic therapies, because it is a platform in which there is minimal disease burden and immunogenic cell death,” Keren Osman, MD, associate professor of medicine, hematology and medical oncology, at Mount Sinai Health System, said during her presentation. “It’s also a platform in which engrafting the immune system may be amenable to antitumor immunity. Some studies have shown that competence to vaccines can be restored by infusing some peripheral blood lymphocytes.”

Elotuzumab (Empliciti, Bristol-Myers Squibb) — approved for the treatment of patients with relapsed multiple myeloma in combination with lenalidomide (Revlimid, Celgene) and dexamethasone — is a humanized monoclonal antibody directed against SLAMF7.

Osman and colleagues hypothesized that the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard-of-care autologous HSCT plus lenalidomide maintenance would be safe and feasible.

Safety and tolerability served as the primary study endpoint. Secondary objectives included to assess myeloma disease status and PFS 1 year after treatment.

Researchers enrolled 15 patients, 13 of whom completed the study protocol, which included undergoing steady-state leukopheresis for PBMC collection, in addition to standard peripheral blood stem cell mobilization and harvest. Patients received standard melphalan conditioning and autologous stem cell rescue.

On day 3 following stem cell infusion, researchers reinfused PBMC cells. On day 4, patients commenced 20 mg/kg IV elotuzumab every 28 days up to 12 cycles. Patients began 10 mg oral lenalidomide maintenance on days 1 through 21 and could continue treatment off study following cycle 12 at the investigator’s discretion.

Two patients did not complete the protocol — one who achieved a very good partial response and discontinued due to personal choice, and one due to early progression.

At 90 days, researchers observed a 13% stringent complete response rate, 27% complete response rate, and 40% very good partial response rate. One-year post autologous HSCT, stringent complete response increased to 33%, complete response was 7%, and very good partial response remained at 40%.

Most adverse events were grade 2 or lower. The autologous HSCT procedure caused most grade 3 or worse hematologic adverse events — which included anemia, neutropenia, lymphopenia and thrombocytopenia — and nonhematologic adverse events, including nausea, vomiting and dehydration, according to the researchers.

Delay in hematopoietic reconstitution occurred in one patient, resulting in hospitalization for 21 days. Also, researchers observed grade 3 hypertension in one patient, which resolved with supportive care, and grade 3 lymphopenia in eight patients during the maintenance phase.

Researchers conducted T-cell receptor sequencing and found 12 of 15 patients had stable or increased productive clonality, a measure of oligoclonal expansion.

“These results suggest elotuzumab and lenalidomide may support persistence or increases in clonal T-cell populations posttransplant,” Osman said.

A phase 2 study is planned, she added. – by Alexandra Todak

Reference:

Osman K, et al. Abstract 26. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.

Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.