Introduction: AL amyloidosis remains a challenge to treat due to relapse even with the use of novel agents as well as high dose melphalan and autologous hematopoietic cell transplant (HCT). Daratumumab (DARA), an anti-CD38 human monoclonal antibody, is highly effective in patients with multiple myeloma and has been approved for that purpose.

Given that there are only 27 patient reports on safety and efficacy of DARA in AL amyloidosis (Kaufman et al. Blood 2017 and Sher et al. Blood 2016), we report on our experience with DARA in pretreated AL amyloidosis patients.

Methods:Patients were identified through our IRB-approved plasma cell disorder patient registry and their medical records reviewed to confirm treatment safety and response. DARA was administered at the standard dosing of 16 mg/kg weekly for 8 doses, then every 2 weeks for 8 doses, then every 4 weeks until disease progression.

Results: We conducted a retrospective analysis which identified 15 adult patients with AL amyloidosis treated at the Cleveland Clinic with DARA monotherapy. DARA was initiated at any time between December 2015 and February 2017 upon evidence of biochemical or organ relapse. The median age was 61 years (range, 40-88) with 53% of the patients being male. One of the patients had symptomatic myeloma by the current International Myeloma Working Group (IMWG) criteria. The median number of prior lines of therapy was 4. Sixty percent of our patient cohort had previously undergone high dose melphalan and autologous HCT. Prior to DARA, 53% had achieved at least a hematologic partial response (PR) with 40% having achieved a hematologic very good partial response (VGPR). Five patients had either cardiac or renal involvement only. Two patients had tongue involvement only and three had both cardiac and renal involvement.

The overall hematologic response rate to DARA was 82% (9 patients achieved at least a VGPR out of 11 patients assessable for hematologic response). A VGPR was achieved in 8 patients (73%) and one patient attained a complete remission (CR). The median time to hematologic response was 4 weeks. The median time of exposure to DARA was 10 weeks. Organ response was measured according to consensus guidelines (Comenzo et al. Leukemia 2012, Palladini et al. JCO 2012). Half of the patients with cardiac involvement (4 out of 8) had a cardiac response while 3 out of the 5 patients with renal involvement had a renal response (60%).

Most of the reported toxicities were grade 1 and 2. The drug was discontinued in two patients due to safety issues (debilitating fatigue after 3 months of DARA in one patient and a facial rash after one a single DARA infusion in the other). Table 1 below shows the safety data.

Conclusion: Our analysis shows that DARA is safe and highly effective in most patients with AL amyloidosis who have undergone previous treatment. It can induce rapid hematologic as well as meaningful organ response. There is hope for regulatory authority approval of DARA in AL amyloidosis with an upcoming randomized trial in newly diagnosed patients. There is also an expectation of less risk of volume overload in cardiac patients as subcutaneous DARA use moves toward approval.


Valent: Celgene Corporation: Speakers Bureau; Takeda: Speakers Bureau.

Author notes


Asterisk with author names denotes non-ASH members.