At ASH 2024 in San Diego this year, AMaRC along with the ALLG presented a poster showcasing the results of an interim analysis of the 'Frail' stratum (Arm 3A and 3B) from the FRAIL-M study. The analysis explored the primary endpoint: Overall response rate (ORR) and safety as indicated by occurrence of deliverability-limiting toxicity (DeLT) after 4 cycles of treatment. Arm 3A consisted of Bortezomib-Dexamethasone (Vd; Dose Level 0) or Bortezomib-Lenalidomide-Dexamethasone (VRd; Dose Level +1). Arm 3B is Lenalidomide-dexamethasone (Ld; Dose Level 0).

Arm 3A: Although efficacy appears to be much improved in 3A, following dose-escalated incorporation of lenalidomide to a dose-reduced VRd triplet (Dose Level 0 to Dose Level +1), deliverability is of some concern as the observed DeLT rate is currently tracking close to the DeLT early-stopping guardrails

Arm 3B: Both efficacy and deliverability are very promising in 3B and support implementation of de-intensification of therapy from a triplet to a doublet in the truly frail TI-NDMM patient. 

Together these findings support not only careful assessment of frailty but also frailty-adapted therapy and question the benefit of attempting triplet and even quadruplet induction in the  truly frail TI-NDMM.