Individualized dynamic frailty-tailored therapy (DynaFiT) in elderly patients with newly diagnosed multiple myeloma: a prospective study

J Hematol Oncol. 2024 Jun 24;17(1):48. doi: 10.1186/s13045-024-01569-y.

Abstract

It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.

Trial registration: ClinicalTrials.gov NCT06099912.

Keywords: Dynamics; Elderly; Frailty; Frailty-tailored therapy; Multiple myeloma.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bortezomib / administration & dosage
  • Bortezomib / therapeutic use
  • Dexamethasone* / administration & dosage
  • Dexamethasone* / therapeutic use
  • Female
  • Frail Elderly
  • Frailty*
  • Geriatric Assessment / methods
  • Humans
  • Lenalidomide* / administration & dosage
  • Lenalidomide* / therapeutic use
  • Male
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / therapy
  • Precision Medicine / methods
  • Prospective Studies

Substances

  • Dexamethasone
  • Lenalidomide
  • Bortezomib
  • daratumumab
  • Antibodies, Monoclonal

Associated data

  • ChiCTR/ChiCTR2100050220
  • ClinicalTrials.gov/NCT06099912