P-345: A prospective cohort study of the effect of second-line induction intensification in suboptimal responders to first-line induction in newly diagnosed transplantation eligible multiple myeloma

Introduction: For multiple myeloma (MM) eligible for autologous stem cell transplantation(ASCT), 4-6 cycles of first-line induction followed by ASCT is the preferred recommendation by guidelines. Deeper pre-ASCT responses are associated with improved progression-free survival (PFS) after transplantation. It is still controversial whether sub-optimal responders to first-line induction should go to ASCT immediately or be switched to a second-line induction regimen to improve the level of response. This prospective cohort study will assess the effect of second-line induction on the response rates, progression free survival (PFS) and overall survival (OS) among patients achieving a suboptimal response (defined as less than complete response (CR)) to first-line induction of newly diagnosed transplantation eligible MM(ND TEMM).

Methods: This is a non-randomized prospective cohort study. TENDMM achieving a suboptimal response (defined as less than CR) to first-line induction are included and was analyzed in two cohorts: those who received second-line induction after non-response to first line therapy and then proceeded to ASCT (cohort A) and those who had no additional induction chemotherapy but proceeded to ASCT immediately (cohort B). This is an observational study, and the decision to intensify induction therapy or not is made by the clinician as well as the patient. The primary endpoints were PFS and OS from induction intensification. Secondary endpoints were response (including the proportion of conversions from ≤VGPR to CR in cohort B) and toxicity. Here, we report the preliminary data of response and safety analysis of second-line induction.

Results: We identified 11 patients with MM who achieved less than a CR to first-line induction chemotherapy between Jan 2024 and May 2024, including two cohorts:cohort A (n=2) and cohort B (n=9). The regimens of first-line induction included VRD(boetezomib/lenalidomide/dexamethasone) and PAD(boetezomib/liposomal doxorubincin/dexamethasone). The regimen of second-line induction included Dara-KPD(daratumumab/carfilzomib/pomalidomide/dexamethasone). Among 7/9 evaluable patients in cohort B, second-line induction intensification resulted in deepening responses in 100.0% (CR in 57.1% and VGPR in 42.9%). Grade 3-4 treatment related adverse event were neutropenia (42.9%), Covid-19 infection (28.6%), pneumonia(14.3%) and rashes (28.6%). Rate of treatment related mortality was 0%.

Conclusions: In conclusion, for patients achieving a less than VGPR to first-line induction therapy including with novel agent combinations, seconde-line induction intensification improved the depth of response. The study is ongoing, longer follow-up is needed to evaluate safety and efficacy of second-line treatment intensification in patients with sub-optimal pre-ASCT responses to first-line induction therapy.