Regimen deemed ‘safe and feasible’ in MM

Keren Osman, MD

SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.

Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.

The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.

The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.

Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.

Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.

“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.

She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.

Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).

The patients had a median of 174 days since diagnosis (range, 98-393).

All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.

Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.

Treatment

Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.

They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.

Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.

Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.

Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.

Safety

“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”

One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.

One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.

Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.

Efficacy

At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).

At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.

“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”

At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.

So the 1-year progression-free survival rate was 86% (13/15).

“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”

*Information in the abstract differs from the presentation.

Keren Osman, MD

SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.

Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.

The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.

The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.

Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.

Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.

“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.

She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.

Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).

The patients had a median of 174 days since diagnosis (range, 98-393).

All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.

Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.

Treatment

Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.

They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.

Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.

Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.

Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.

Safety

“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”

One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.

One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.

Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.

Efficacy

At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).

At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.

“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”

At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.

So the 1-year progression-free survival rate was 86% (13/15).

“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”

*Information in the abstract differs from the presentation.

Keren Osman, MD

SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.

Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.

The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.

The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.

Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.

Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.

“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.

She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.

Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).

The patients had a median of 174 days since diagnosis (range, 98-393).

All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.

Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.

Treatment

Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.

They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.

Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.

Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.

Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.

Safety

“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”

One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.

One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.

Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.

Efficacy

At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).

At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.

“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”

At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.

So the 1-year progression-free survival rate was 86% (13/15).

“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”

*Information in the abstract differs from the presentation.