Frontline Induction Therapy for Transplant-Ineligible or Transplant-Deferred Patients

Frontline Induction Therapy for Transplant-Ineligible Patients

For frail and transplant-ineligible patients, treatment goals differ fundamentally from those for fit patients, focusing on symptom control and quality of life rather than achieving maximal depth of response. Proteasome inhibitor selection and dexamethasone dosing require significant modification, with dexamethasone doses reduced to 8-12 mg rather than standard 20-40 mg doses used in trials. Short dexamethasone pulses may benefit patients with severe bone pain, but routine use of high-dose steroids should be avoided.

The published trials in transplant-ineligible patients (Cepheus, Imroz, and Benefit) excluded patients over age 80, limiting applicability to the very elderly population often treated with lenalidomide plus dexamethasone for its favorable tolerability. Many patients classified as transplant-ineligible in European practice might be considered transplant-eligible at some US centers, creating challenges in applying trial data. Using intensive induction as a "stress test" to assess fitness for transplant represents one strategy for borderline candidates.

For fit patients over age 75, the relative benefit of transplant remains substantial, with magnitude similar to younger patients. Long-term data from trials like Perseus suggest median progression-free survival exceeding 10-12 years with transplant-inclusive approaches, representing meaningful benefit even for older fit patients. Deferring transplant at age 75 often means never receiving transplant, potentially compromising long-term outcomes. For younger patients declining transplant despite fitness, quadruplet induction provides reassurance of excellent disease control, with other treatment options remaining available at relapse.