Contributions
Abstract: EP968
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Quadruplet treatment regimens including a proteasome inhibitor, immunomodulating agent and a monoclonal antibody are playing an emerging role in front-line treatment of multiple myeloma (MM). Recently, a randomized phase II trial (SWOG-1211, Usmani SZ et al., Lancet Haematology, 2021) comparing lenalidomide, bortezomib and dexamethasone (RVD) with or without the anti-SLAMF7 monoclonal antibody (moAb) elotuzumab (Elo) found no significant differences in response rates, progression-free survival (PFS) nor overall survival (OS) in high-risk newly diagnosed patients with high-risk MM.
Aims
We aimed to compare available response rates after induction therapy with RVD vs. Elo-RVD according to high-risk subgroups from our randomized phase III HD6 trial (NCT 02495922).
Methods
The German-speaking Myeloma Multicenter Group (GMMG) HD6 trial is a randomized multicenter phase III treatment protocol including 559 and 555 newly diagnosed transplantation-eligible MM patients in the intention-to-treat (ITT) and safety population, respectively. Induction therapy consisted of four 21-day cycles of RVD (arms A1+A2, n=280) or Elo-RVD (arms B1+B2, n=279). Exploratory analyses on response rates (very good partial response or better, ≥VGPR) according to predefined subgroups comparing RVD vs. Elo-RVD induction therapy will be presented.
Results
Median patient age was 59 (27-70) years at trial inclusion. Revised International Staging System (R-ISS), ISS stages, adverse cytogenetics (at least one of the following: del17p13, t(4;14), t(14;16) and the proportion of patients with renal impairment (either serum creatinine >2 mg/dl or glomerular filtration rate <40 ml/min) were equally distributed among the RVD and Elo-RVD groups. Revised ISS stages I / II / III were noted in 29.9% / 59.3% / 10.9% of patients in the RVD cohort vs. 28.1% / 58.1% / 13.8% in the Elo-RVD group. At least four cycles of preplanned RVD or Elo-RVD induction therapy were completed by 264 (94.3%) and 258 (92.5%) patients. The overall response rates (ORR, ≥PR) after the fourth cycle of induction therapy were 85.6% in the RVD group and 82.4% in the Elo-RVD group (Fisher p=0.53). Deep responses (very good partial response rates or better, ≥VGPR) were reached by 54.0% in the RVD group vs. 58.3% in the Elo-RVD group (Fisher p=0.22). The rates of ≥VGPR between RVD and Elo-RVD were significantly different in patients with R-ISS stage II (50.8% vs. 64.5%, Fisher p=0.03; odds ratio [OR]=1.83, 95% confidence interval [95% CI]: 1.09-3.07, Wald p=0.02). Borderline significant results were observed for patients with normal renal function (52.9% vs. 59.8%, Fisher p=0.07; OR=1.40, 95% CI: 0.98-2.01, Wald p=0.06). No differences were observed in other prognostically important subgroups such as in patients with renal impairment at baseline, with or without adverse cytogenetics, good (0-1) or poor (>1) World Health Organization (WHO) performance status or R-ISS stages I and III. Further analyses on toxicities and dose intensities of RVD vs. Elo-RVD are planned.
Conclusion
Addition of Elo to RVD improves the rate of deep responses (≥VGPR) post induction therapy in patients with R-ISS stage II, prognostically a rather heterogenous group of MM. Further subgroups that benefit from Elo-RVD vs. RVD regarding response post induction therapy could not be identified. However, benefit by the addition of monoclonal antibodies often becomes obvious during further treatment course (Moreau P et al., The Lancet, 2019). Final results for the primary endpoint of the HD6 trial (PFS) will be reported in late 2021.
Keyword(s): High risk, Induction chemotherapy, Multiple myeloma, Transplant
Abstract: EP968
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Quadruplet treatment regimens including a proteasome inhibitor, immunomodulating agent and a monoclonal antibody are playing an emerging role in front-line treatment of multiple myeloma (MM). Recently, a randomized phase II trial (SWOG-1211, Usmani SZ et al., Lancet Haematology, 2021) comparing lenalidomide, bortezomib and dexamethasone (RVD) with or without the anti-SLAMF7 monoclonal antibody (moAb) elotuzumab (Elo) found no significant differences in response rates, progression-free survival (PFS) nor overall survival (OS) in high-risk newly diagnosed patients with high-risk MM.
Aims
We aimed to compare available response rates after induction therapy with RVD vs. Elo-RVD according to high-risk subgroups from our randomized phase III HD6 trial (NCT 02495922).
Methods
The German-speaking Myeloma Multicenter Group (GMMG) HD6 trial is a randomized multicenter phase III treatment protocol including 559 and 555 newly diagnosed transplantation-eligible MM patients in the intention-to-treat (ITT) and safety population, respectively. Induction therapy consisted of four 21-day cycles of RVD (arms A1+A2, n=280) or Elo-RVD (arms B1+B2, n=279). Exploratory analyses on response rates (very good partial response or better, ≥VGPR) according to predefined subgroups comparing RVD vs. Elo-RVD induction therapy will be presented.
Results
Median patient age was 59 (27-70) years at trial inclusion. Revised International Staging System (R-ISS), ISS stages, adverse cytogenetics (at least one of the following: del17p13, t(4;14), t(14;16) and the proportion of patients with renal impairment (either serum creatinine >2 mg/dl or glomerular filtration rate <40 ml/min) were equally distributed among the RVD and Elo-RVD groups. Revised ISS stages I / II / III were noted in 29.9% / 59.3% / 10.9% of patients in the RVD cohort vs. 28.1% / 58.1% / 13.8% in the Elo-RVD group. At least four cycles of preplanned RVD or Elo-RVD induction therapy were completed by 264 (94.3%) and 258 (92.5%) patients. The overall response rates (ORR, ≥PR) after the fourth cycle of induction therapy were 85.6% in the RVD group and 82.4% in the Elo-RVD group (Fisher p=0.53). Deep responses (very good partial response rates or better, ≥VGPR) were reached by 54.0% in the RVD group vs. 58.3% in the Elo-RVD group (Fisher p=0.22). The rates of ≥VGPR between RVD and Elo-RVD were significantly different in patients with R-ISS stage II (50.8% vs. 64.5%, Fisher p=0.03; odds ratio [OR]=1.83, 95% confidence interval [95% CI]: 1.09-3.07, Wald p=0.02). Borderline significant results were observed for patients with normal renal function (52.9% vs. 59.8%, Fisher p=0.07; OR=1.40, 95% CI: 0.98-2.01, Wald p=0.06). No differences were observed in other prognostically important subgroups such as in patients with renal impairment at baseline, with or without adverse cytogenetics, good (0-1) or poor (>1) World Health Organization (WHO) performance status or R-ISS stages I and III. Further analyses on toxicities and dose intensities of RVD vs. Elo-RVD are planned.
Conclusion
Addition of Elo to RVD improves the rate of deep responses (≥VGPR) post induction therapy in patients with R-ISS stage II, prognostically a rather heterogenous group of MM. Further subgroups that benefit from Elo-RVD vs. RVD regarding response post induction therapy could not be identified. However, benefit by the addition of monoclonal antibodies often becomes obvious during further treatment course (Moreau P et al., The Lancet, 2019). Final results for the primary endpoint of the HD6 trial (PFS) will be reported in late 2021.
Keyword(s): High risk, Induction chemotherapy, Multiple myeloma, Transplant