Second transplant, consolidation don’t add benefit in upfront multiple myeloma therapy

 

SAN DIEGO – It took a clinical trial with a byzantine design to prove it, but neither posttransplant consolidation therapy nor second transplant offered any additional survival benefits to patients with multiple myeloma, including patients with high-risk disease who were treated with an upfront thalidomide analogue and a proteasome inhibitor, followed by stem cell transplant and lenalidomide maintenance.

Among 758 patients with multiple myeloma who underwent standard induction therapy, followed by melphalan conditioning and autologous stem cell transplant (ASCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) among patients assigned to follow-on therapy with either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant, followed by lenalidomide maintenance, reported  Edward A. Stadtmauer, MD, coleader of the hematologic malignancies program at the Abramson Cancer Center, and chief of the section of hematologic malignancies, University of Pennsylvania, Philadelphia.

Neil Osterweil/Frontline Medical News

“In the era of thalidomide analogues and proteasome inhibitors used in the initial therapy for myeloma – in this study over 90% of the patients were exposed to either one of them and greater than 50% were exposed to both of them prior to enrolling on the study – and the use of prolonged maintenance therapy with lenalidomide, posttransplant consolidation with cycles of RVD or a second transplant do not produce incremental progression-free survival benefit,” he said at the annual meeting of the American Society of Hematology.

Investigators in the STAMINA (Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma) trial (BMT CTN 0702) hypothesized that the use of thalidomide analogues and proteasome inhibitors used in first-line therapy, consolidation, and long-term maintenance after high-dose melphalan and ASCT would improve survival, compared with a second ASCT.

To test this idea, they enrolled 758 patients and randomized them to one of the three aforementioned posttransplant strategies prior to transplant conditioning with high-dose melphalan (200 mg/m²) and ASCT.

Roughly 25% of patients in each treatment arm had high-risk disease, defined as beta₂ microglobulin levels greater than 5.5 mg/L, high-risk cytogenetics, and deletion 13 detected by standard cytogenetics only. The remaining patients in each arm had standard-risk disease.

Slightly more than half of patients received RVD upfront; about 13% received cyclophosphamide, bortezomib, and dexamethasone (CyBorD); roughly 10% received lenalidomide dexamethasone; 12% were treated with bortezomib/dexamethasone; and about 8% received other, unspecified combinations.

At a median follow-up time of 37.8 months, the PFS rate, which was the primary endpoint, was 56.5% for the second transplant arm, 56.7% for the RVD arm, and 52.2% for the maintenance-only arm. The differences were not statistically significant.

Similarly, there were no among-arm differences in PFS for patients with standard-risk disease (60.9%, 59.5%, and 55.9%) or for those with high-risk myeloma (42.2%, 48.3%, and 40.2%)

Overall survival, a secondary endpoint, was also not significantly different among the groups, at 82%, 85.7%, and 83.4%, respectively.

Encouragingly, however, despite lower PFS rates, patients with high-risk disease had high OS rates, with 79.6% of patients in the double-transplant arm, 77.5% of those in the RVD consolidation arm, and 79.5% of those in the lenalidomide maintenance-alone arm still alive at 38 months.

Secondary malignancies occurred among 5.1% of patients overall: 14 in the dual-transplant arm, 15 in the consolidation arm, and 10 in the maintenance-only arm. The most frequently reported second malignancies were leukemia, which occurred in 3 of 14 patients with second cancers after second transplant and in 9 of 15 patients with second cancers after consolidation, and solid tumors, which occurred most frequently among second cancers in the maintenance arm.

The investigators are continuing to parse the data by study arm to see whether response assessment correlates with outcomes and with complete remissions. They also plan to examine minimal residual disease via flow cytometry and sequencing, and to obtain long-term data on survival, toxicities, and second primary malignancies.

The trial was funded by the National Institutes of Health with support from Celgene and Millennium/Takeda. Dr. Stadtmauer disclosed consulting for Takeda and travel expenses from Celgene. 

 

SAN DIEGO – It took a clinical trial with a byzantine design to prove it, but neither posttransplant consolidation therapy nor second transplant offered any additional survival benefits to patients with multiple myeloma, including patients with high-risk disease who were treated with an upfront thalidomide analogue and a proteasome inhibitor, followed by stem cell transplant and lenalidomide maintenance.

Among 758 patients with multiple myeloma who underwent standard induction therapy, followed by melphalan conditioning and autologous stem cell transplant (ASCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) among patients assigned to follow-on therapy with either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant, followed by lenalidomide maintenance, reported  Edward A. Stadtmauer, MD, coleader of the hematologic malignancies program at the Abramson Cancer Center, and chief of the section of hematologic malignancies, University of Pennsylvania, Philadelphia.

Neil Osterweil/Frontline Medical News

“In the era of thalidomide analogues and proteasome inhibitors used in the initial therapy for myeloma – in this study over 90% of the patients were exposed to either one of them and greater than 50% were exposed to both of them prior to enrolling on the study – and the use of prolonged maintenance therapy with lenalidomide, posttransplant consolidation with cycles of RVD or a second transplant do not produce incremental progression-free survival benefit,” he said at the annual meeting of the American Society of Hematology.

Investigators in the STAMINA (Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma) trial (BMT CTN 0702) hypothesized that the use of thalidomide analogues and proteasome inhibitors used in first-line therapy, consolidation, and long-term maintenance after high-dose melphalan and ASCT would improve survival, compared with a second ASCT.

To test this idea, they enrolled 758 patients and randomized them to one of the three aforementioned posttransplant strategies prior to transplant conditioning with high-dose melphalan (200 mg/m²) and ASCT.

Roughly 25% of patients in each treatment arm had high-risk disease, defined as beta₂ microglobulin levels greater than 5.5 mg/L, high-risk cytogenetics, and deletion 13 detected by standard cytogenetics only. The remaining patients in each arm had standard-risk disease.

Slightly more than half of patients received RVD upfront; about 13% received cyclophosphamide, bortezomib, and dexamethasone (CyBorD); roughly 10% received lenalidomide dexamethasone; 12% were treated with bortezomib/dexamethasone; and about 8% received other, unspecified combinations.

At a median follow-up time of 37.8 months, the PFS rate, which was the primary endpoint, was 56.5% for the second transplant arm, 56.7% for the RVD arm, and 52.2% for the maintenance-only arm. The differences were not statistically significant.

Similarly, there were no among-arm differences in PFS for patients with standard-risk disease (60.9%, 59.5%, and 55.9%) or for those with high-risk myeloma (42.2%, 48.3%, and 40.2%)

Overall survival, a secondary endpoint, was also not significantly different among the groups, at 82%, 85.7%, and 83.4%, respectively.

Encouragingly, however, despite lower PFS rates, patients with high-risk disease had high OS rates, with 79.6% of patients in the double-transplant arm, 77.5% of those in the RVD consolidation arm, and 79.5% of those in the lenalidomide maintenance-alone arm still alive at 38 months.

Secondary malignancies occurred among 5.1% of patients overall: 14 in the dual-transplant arm, 15 in the consolidation arm, and 10 in the maintenance-only arm. The most frequently reported second malignancies were leukemia, which occurred in 3 of 14 patients with second cancers after second transplant and in 9 of 15 patients with second cancers after consolidation, and solid tumors, which occurred most frequently among second cancers in the maintenance arm.

The investigators are continuing to parse the data by study arm to see whether response assessment correlates with outcomes and with complete remissions. They also plan to examine minimal residual disease via flow cytometry and sequencing, and to obtain long-term data on survival, toxicities, and second primary malignancies.

The trial was funded by the National Institutes of Health with support from Celgene and Millennium/Takeda. Dr. Stadtmauer disclosed consulting for Takeda and travel expenses from Celgene. 

 

SAN DIEGO – It took a clinical trial with a byzantine design to prove it, but neither posttransplant consolidation therapy nor second transplant offered any additional survival benefits to patients with multiple myeloma, including patients with high-risk disease who were treated with an upfront thalidomide analogue and a proteasome inhibitor, followed by stem cell transplant and lenalidomide maintenance.

Among 758 patients with multiple myeloma who underwent standard induction therapy, followed by melphalan conditioning and autologous stem cell transplant (ASCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) among patients assigned to follow-on therapy with either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant, followed by lenalidomide maintenance, reported  Edward A. Stadtmauer, MD, coleader of the hematologic malignancies program at the Abramson Cancer Center, and chief of the section of hematologic malignancies, University of Pennsylvania, Philadelphia.

Neil Osterweil/Frontline Medical News

“In the era of thalidomide analogues and proteasome inhibitors used in the initial therapy for myeloma – in this study over 90% of the patients were exposed to either one of them and greater than 50% were exposed to both of them prior to enrolling on the study – and the use of prolonged maintenance therapy with lenalidomide, posttransplant consolidation with cycles of RVD or a second transplant do not produce incremental progression-free survival benefit,” he said at the annual meeting of the American Society of Hematology.

Investigators in the STAMINA (Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma) trial (BMT CTN 0702) hypothesized that the use of thalidomide analogues and proteasome inhibitors used in first-line therapy, consolidation, and long-term maintenance after high-dose melphalan and ASCT would improve survival, compared with a second ASCT.

To test this idea, they enrolled 758 patients and randomized them to one of the three aforementioned posttransplant strategies prior to transplant conditioning with high-dose melphalan (200 mg/m²) and ASCT.

Roughly 25% of patients in each treatment arm had high-risk disease, defined as beta₂ microglobulin levels greater than 5.5 mg/L, high-risk cytogenetics, and deletion 13 detected by standard cytogenetics only. The remaining patients in each arm had standard-risk disease.

Slightly more than half of patients received RVD upfront; about 13% received cyclophosphamide, bortezomib, and dexamethasone (CyBorD); roughly 10% received lenalidomide dexamethasone; 12% were treated with bortezomib/dexamethasone; and about 8% received other, unspecified combinations.

At a median follow-up time of 37.8 months, the PFS rate, which was the primary endpoint, was 56.5% for the second transplant arm, 56.7% for the RVD arm, and 52.2% for the maintenance-only arm. The differences were not statistically significant.

Similarly, there were no among-arm differences in PFS for patients with standard-risk disease (60.9%, 59.5%, and 55.9%) or for those with high-risk myeloma (42.2%, 48.3%, and 40.2%)

Overall survival, a secondary endpoint, was also not significantly different among the groups, at 82%, 85.7%, and 83.4%, respectively.

Encouragingly, however, despite lower PFS rates, patients with high-risk disease had high OS rates, with 79.6% of patients in the double-transplant arm, 77.5% of those in the RVD consolidation arm, and 79.5% of those in the lenalidomide maintenance-alone arm still alive at 38 months.

Secondary malignancies occurred among 5.1% of patients overall: 14 in the dual-transplant arm, 15 in the consolidation arm, and 10 in the maintenance-only arm. The most frequently reported second malignancies were leukemia, which occurred in 3 of 14 patients with second cancers after second transplant and in 9 of 15 patients with second cancers after consolidation, and solid tumors, which occurred most frequently among second cancers in the maintenance arm.

The investigators are continuing to parse the data by study arm to see whether response assessment correlates with outcomes and with complete remissions. They also plan to examine minimal residual disease via flow cytometry and sequencing, and to obtain long-term data on survival, toxicities, and second primary malignancies.

The trial was funded by the National Institutes of Health with support from Celgene and Millennium/Takeda. Dr. Stadtmauer disclosed consulting for Takeda and travel expenses from Celgene.