The role of novel agents for consolidation after autologous transplantation in newly diagnosed multiple myeloma: a systematic review

TY - JOUR

T1 - The role of novel agents for consolidation after autologous transplantation in newly diagnosed multiple myeloma: a systematic review

AU - Gagelmann, Nico

AU - Kröger, Nicolaus

PY - 2021/2

Y1 - 2021/2

N2 - Despite the increasing inclusion of novel agents within the multiple myeloma (MM) treatment sequence, their role for posttransplant consolidation therapy remains unclear. We systematically reviewed studies evaluating the efficacy of novel agent consolidation. We identified 11 citations on 12 prospective comparative studies, and 5 citations were single-arm or comparative studies with preliminary results. Nine different regimens were evaluated in 5905 patients. Risk assessment yielded serious risk of bias and heterogeneity across study designs was high. Irrespective of the regimen, deepened responses after consolidation were seen and improvements were more pronounced with multi-agent consolidation. Bortezomib, thalidomide, and dexamethasone improved long-term survival versus duplet consolidation, including in patients with high-risk cytogenetics. The addition of daratumumab to triplet regimens yielded modestly improved responses with significantly increased rates of minimal residual disease negativity but survival results were limited by short follow-up. In high-risk MM, responses were not different, whereas progression-free survival appeared to be improved with consolidation therapy, challenging the association of response and overall outcome in this subgroup. Our findings highlight the necessity of longer follow-up and consistent reporting to ensure comparability of studies to enable better evidence assessment and to identify patients benefitting from consolidation therapy.

AB - Despite the increasing inclusion of novel agents within the multiple myeloma (MM) treatment sequence, their role for posttransplant consolidation therapy remains unclear. We systematically reviewed studies evaluating the efficacy of novel agent consolidation. We identified 11 citations on 12 prospective comparative studies, and 5 citations were single-arm or comparative studies with preliminary results. Nine different regimens were evaluated in 5905 patients. Risk assessment yielded serious risk of bias and heterogeneity across study designs was high. Irrespective of the regimen, deepened responses after consolidation were seen and improvements were more pronounced with multi-agent consolidation. Bortezomib, thalidomide, and dexamethasone improved long-term survival versus duplet consolidation, including in patients with high-risk cytogenetics. The addition of daratumumab to triplet regimens yielded modestly improved responses with significantly increased rates of minimal residual disease negativity but survival results were limited by short follow-up. In high-risk MM, responses were not different, whereas progression-free survival appeared to be improved with consolidation therapy, challenging the association of response and overall outcome in this subgroup. Our findings highlight the necessity of longer follow-up and consistent reporting to ensure comparability of studies to enable better evidence assessment and to identify patients benefitting from consolidation therapy.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Bortezomib/therapeutic use

KW - Consolidation Chemotherapy

KW - Dexamethasone/therapeutic use

KW - Female

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Male

KW - Middle Aged

KW - Multiple Myeloma/diagnosis

KW - Risk Assessment

KW - Thalidomide/therapeutic use

KW - Transplantation, Autologous

U2 - 10.1007/s00277-020-04316-8

DO - 10.1007/s00277-020-04316-8

M3 - SCORING: Review article

C2 - 33123798

VL - 100

SP - 405

EP - 419

JO - ANN HEMATOL

JF - ANN HEMATOL

SN - 0939-5555

IS - 2

ER -