MD Hospital Universitario de Salamanca Salamanca, Castilla y Leon, Spain
Introduction: AL amyloidosis is an uncommon plasma cell dyscrasia with a heterogeneous prognosis, highlighting very poor survival of patients with stage III-IV revised 2012 Mayo Clinic. However, the arrival of proteasome inhibitors (PI), and especially anti-CD38 MoAb, daratumumab (dara), have represented a paradigm shift in the treatment of this disease.
Aim: To investigate whether hematological (HR) and progression-free survival (PFS) improved in patients with AL amyloidosis according to induction therapies.
Methods: An observational and retrospective study was designed including 92 patients with AL amyloidosis consecutively treated in Salamanca between 1999 and 2023. Induction treatments were grouped into chemotherapy (chemo), including patients who directly underwent to autologous stem cell transplantation, and new drug-based schemes (PI, immunomodulators [IMiD] or dara): PI/IMiD and dara+PI.
Results: Median age at diagnosis was 64 years (range, 39-90), 53.7% were men. Fifteen (18.1%), 24 (28.9%), 19 (22.9%) and 25 (30.1%) patients presented revised 2012 Mayo Clinic stage I, II, III and IV, respectively. Twenty-one (22.8%) patients received dara+PI-based schemes; 46 (50.0%) patients PI/IMiD-based schemes and 25 (27.2%) patients chemo.
Dara+PI-based schemes resulted in a rate of HR (≥ partial HR) of 100%, significantly higher compared to 78.3% in patients receiving PI/IMiD (P=0.021) and 60.9% with chemo (P=0.001). Likewise, 76.2% of patients treated with dara+PI achieved complete HR (cHR), compared to 37.0% with PI/IMiD (P=0.004) and 13.0% with chemo (P< 0.001). Notably, all the patients at stage III-IV treated with dara+PI achieved HR compared to 70.0% with PI/IMiD (P=0.029) and 55.6% with chemo (P=0.008). In addition, 84.6% of these patients receiving dara+PI achieved cHR compared to 45.0% in patients treated with PI/IMiD (P=0.032) and 11.1% with chemo (P=0.004). Time to HR was shorter in patients treated with dara+PI (28 days) compared to those treated with PI/IMiD (72 days; P< 0.001) and chemo (95 days; P< 0.001) as well as time to cHR (4 months vs. not reached vs. not reached; both P=0.002). This advantage was even noticeably at stage III-IV, both in time to HR (28 vs. 77 vs. 171 days; P=0.002 and 0.005, respectively) and time to cHR (2 vs. 9 months vs. not reached; P=0.090 and P=0.030, respectively).
With a median follow-up of 51.5 months, PFS was prolonged in patients receiving dara+PI (not reached) compared to those treated with PI/IMiD (18.0 months; P=0.040) and chemo (6.0 months; P=0.009). This clinical benefit was more evident in patients at stage III-IV with PFS not reached in patients treated with dara+PI compared to 8.0 months for patients receiving PI/IMiD (P=0.025) and 6.0 months (P=0.009) for those receiving chemo.
Conclusions: The addition of daratumumab to PI in the frontline treatment of AL amyloidosis improved HR and resulted into deeper and faster responses and, subsequently into a significant benefit in PFS for all patients, even those at stage III-IV.