Real World Evidence of Daratumumab-Based Treatment in AL Amyloidosis

Introduction

AL Amyloidosis is a rare plasma cell disorder with poor survival with chemotherapy alone. Autologous transplants have improved outcomes over the years. Still, strategies have not been clearly defined regarding which induction chemotherapy vs. the role of post-transplant maintenance would be beneficial for AL Amyloidosis. Recently, immunotherapies have changed the landscape of the amyloidosis treatment algorithm to offer curative options, even for patients who are not transplant candidates at initial diagnosis.

Patient population and methods

Between January 2007 and July 2024, a total of 57 patients underwent transplant as consolidation therapy for amyloidosis at Penn State Cancer Institute, Milton S. Hershey Medical Center. The median age of the patients (38 M:19 F) was 63 years (range 34-77 years), with a median follow-up of 4.7 years (range 27 days - 17 years). 52 patients (91.2%) were Caucasian, 3 (5.2%) African American, and 2 (3.5%) other. At the time of transplant, 19 patients (33.3%) had complete response, 3 (5.3%) had very good partial response, 19 (33.3%) had partial response, and 16 (28.1%) had refractory or active disease. Organ involvement was significant, with 36 patients (63.1%) with involvement of < 3 organs and 21 patients (36.8%) having ≥ 3 organs involved. Cardiac involvement was seen in 37 patients (64.9%), and kidney involvement was seen in 44 patients (77.1%). All 57 patients (100%) received autologous transplants with melphalan conditioning. Post-transplant maintenance therapy was administered in 27 patients (47.3%) after 2015 and only one patient (1.7%) before 2015. Among those who received Daratumumab (Dara)-based induction therapy, organ involvements were as follows: cardiac involvement (n=14); kidneys (n=21); liver (n=5); and other organs (n=5). The data was collected retrospectively, and overall survival (OS) was analyzed using the Kaplan-Meier method for all patients with available data.

Outcomes

The OS rate for patients who underwent autologous transplants was 71.8% at 5 years, regardless of their pre and post-transplant treatments. Patients with cardiac involvement had poorer outcomes compared to those without cardiac involvement, with 5-year OS rates of 62.1% and 94.1%, respectively (p=0.031). The 5-year OS for autologous transplant was 62.1% for cardiac amyloid, 68.0% for kidney-only amyloid, and 68.1% for multiple organ (≥3 organs) involvement. The 1-year, 3-year, and 5-year OS rates for amyloidosis with concurrent myeloma were 91.6%, 56.2%, and 46.8%, respectively.

5-year OS was 91.6% for patients who received Dara-CyBorD induction vs. 82.5% for those who received CyBorD (p=0.95). Additionally, the 5-year OS for patients who received daratumumab maintenance was 95.2% compared to 88.8% for those who received non-dara-based maintenance (p=0.35). The patients who did not receive any maintenance had the worst outcome, with a 5-year OS of 50.6% (p=0.027). The primary causes of death were disease progression (n=5), transplant-related mortality (n=4) [major bleeding events n=2, cardiac failure due to cardiac amyloidosis n=2], and unknown causes (n=4).

Conclusion

Significantly better outcomes were observed in AL amyloidosis patients without cardiac involvement and in those who received either Dara-CyBorD or CyBorD, followed by maintenance therapy, with daratumumab maintenance showing particularly notable benefits. Immunotherapies have changed the landscape of the amyloidosis treatment algorithm and can achieve CR with long-term remission. Randomized studies or larger retrospective CIBMTR data analysis may be essential to answer the best transplant strategy for these patients.

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