Clinical Observation of Daratumumab Based Immunochemotherapy in the Treatment of Light Chain Amyloidosis

Purpose: Systemic light chain (AL) amyloidosis arises from the aberrant folding of monoclonal immunoglobulin light chains, resulting in the formation of amyloid proteins. These proteins are subsequently deposited in various tissues and organs, instigating structural damage, organ impairment, and relentless disease progression. Daratumumab, a fully human IgG1κ monoclonal antibody engineered to target CD38, serves as both a depleting agent for plasma cells and an immunomodulator. In 2021, daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-VCd regimen) became the first formally licensed treatment for AL amyloidosis. Our study, an observational investigation involving five patients diagnosed with AL amyloidosis, aims to demonstrate the efficacy and safety of daratumumab based treatment.

Methods: This clinical observation encompasses five patients, with four undergoing renal biopsies and one undergoing a fat biopsy. All patients were diagnosed with confirmed and symptomatic AL amyloidosis and received treatment with the D-VCd regimen at our institution between August 2021 and August 2023. The treatment protocol involved administering daratumumab at a dose of 16 mg/kg, bortezomib 1.3 mg/m², cyclophosphamide 300 mg/m² (500 mg maximum weekly dose), and dexamethasone 20 mg intravenously. Treatment was initially administered once weekly for weeks 1 to 8, followed by every 2 weeks from weeks 9 to 24 (for all patients), and subsequently extended to every 4 weeks for up to 12 months (only for Pt 3 and Pt 4).

Results: The case series comprises five male individuals with a median age of 66 years (range, 43-73 years). Among these individuals, four patients achieved a hematologic very good partial response (VGPR), two of whom achieved a complete response (CR). The mean difference of serum free light chain (dFLC) value changed from 384.2 mg/L (range, 81.1-926.1) to 95.72 mg/L (range, 0.73-447). Conversely, one patient exhibited no discernible improvement following six months of therapy, prompting the discontinuation of daratumumab. Four patients showed cardiac and renal responses after six cycles of treatment. Remarkably, after 6 cycles of treatment, according to common terminology criteria for adverse events, (CTCAE) assessment, no patients experienced adverse reactions of grade 3 or above.

Conclusions: This study presents our clinical observation of daratumumab based immunochemotherapy for AL amyloidosis, unveiling its safety and efficacy. Notably, 80% (4/5) of patients exhibited hematologic response following six cycles of treatment, devoid of any discernible side effects. Simultaneously, an equivalent proportion of patients 80% (4/5) showcased cardiac and renal responses, underscoring the treatment's effectiveness in preserving organ function and extending patient survival.

No relevant conflicts of interest to declare.