Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) +/- Daratumumab Treatment Results in Sustained Hematologic Response in Patients with AL Amyloidosis: A Retrospective Analysis of Patients at Mayo Clinic

Introduction

Light chain (AL) amyloidosis is a rare plasma cell disorder characterized by amyloid fibril deposition in various organs leading to progressive organ damage. The standard of care therapy has been cyclophosphamide-bortezomib-dexamethasone (CyBorD) until January 2021 when daratumumab was approved by the FDA for use after data from the Phase 3 ANDROMEDA trial revealed improved outcomes with the quadruplet regimen. Here, we retrospectively evaluated the outcomes of patients with newly diagnosed AL amyloidosis treated with CyBorD +/- daratumumab as first line therapy at the Mayo Clinic from 2009 to 2022.

Methods

The study was approved by the Mayo Clinic Institutional Review Board. We performed a retrospective analysis of patients diagnosed with AL amyloidosis between 2009 and 2022 who received CyBorD +/- daratumumab as first line therapy. The regimen consisted of subcutaneous bortezomib (1.3 mg/m² or 1.5mg/m² on days 1, 4, 8, and 11 every 28 days), cyclophosphamide (300mg/m² orally or IV weekly), and dexamethasone (20-40mg orally or IV weekly). In patients who also received daratumumab, dosing was 1,800 mg weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, followed by weekly for any additional cycles. Data extracted from the medical record included patient characteristics, subsequent therapies, labs, rates of relapse, and outcomes.

Results

There were 164 patients available who met criteria for inclusion of newly diagnosed AL amyloidosis. Of the 164, 30 (18.3%) received CyBorD with daratumumab. Mean age at diagnosis was 63.8 years (range, 35-81 years). Most frequent organ involvement included cardiac in 73.8% and kidney in 61.0% patients. Eighty-one percent of patients achieved a hematologic response (defined as complete response in 38% or very good partial response, VGPR, in 43%). No patients were considered eligible for transplant at diagnosis, however after CyBorD +/- daratumumab therapy, 62 (37.8%) received an autologous stem cell transplant (ASCT). Over half of patients received maintenance therapy after initial treatment (53.7%), with daratumumab being the most common maintenance therapy prescribed (62.5%). The most frequent treatment related adverse event included peripheral neuropathy (40.7%), although no patients experienced grade 4 peripheral neuropathy. Forty-five percent of patients experienced cytopenias during treatment, however only <1% required transfusions. There was no difference in treatment related adverse effects with the addition of daratumumab. At 1-year, overall survival was 94% (95% CI 0.90-0.98) and at 5 years, overall survival was 77% (95% CI 0.67-0.87).

Conclusions

In our retrospective analysis, CyBorD +/- daratumumab produced a durable hematologic response in newly diagnosed patients with AL amyloidosis. Although 18% of patients received daratumumab, outcomes were still excellent, with nearly 40% of patients eligible for ASCT after treatment and 5-year overall survival of 77%.

Bergsagel:Oncopeptides: Consultancy; Janssen: Consultancy; GSK: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Fonseca:Adaptive Biotechnologies: Divested equity in a private or publicly-traded company in the past 24 months; Genentech, Pfizer, Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies, Caris Life Sciences, OncoMyx and OncoTracker: Other: Scientific Advisory Board; AbbVie, Amgen, Bayer, BMS/Celgene, GSK, H3 Therapeutics, Janssen, Juno, Karyopharm, Kite, Merck, Novartis, Oncopeptides, OncoTracker, Pfizer, Pharmacyclics, Regeneron, Sanofi, Takeda: Consultancy; Adaptive Biotechnologies, Caris Life Sciences, Oncomyx and OncoTracker: Membership on an entity's Board of Directors or advisory committees; Amgen, BMS, Celgene, Takeda, Bayer, Janssen, Novartis, Pharmacyclics, Sanofi, Merck, Juno, Kite, Aduro, OncoTracker, GSK, AbbVie, Pfizer, Karyopharm.: Consultancy; FIH prognostication in myeloma: Patents & Royalties.