Rare Disease Report

Phase 2 Results Show Benefit of Daratumumab in AL Amyloidosis

DECEMBER 09, 2017
Mathew Shanley
Patients with multiple myeloma (MM), a rare cancer that forms in the plasma and can cause cancer cells to accumulate in the bone marrow, have experienced clinical benefit when treated with the human IgG1k monoclonal antibody daratumumab.

Because daratumumab targets the CD38 surface antigen on plasma cells, and clonal cells do express surface CD38 in relapsed light chain (AL) amyloidosis, there’s reason to believe that the drug will also be effective in this second cancer type.

AL amyloidosis is an ultra-rare plasma cell disorder characterized by the production of immunoglobin light chains misfolding into fibrils that are deposited into the body’s organs. This life-threatening protein buildup can occur in the heart, kidneys, liver, soft tissue, and nervous system, leading to multi-organ failure. An estimated 70% of all AL amyloidosis patients have accumulations of amyloid in the cardiac tissue, and no therapies are currently approved for the treatment of this condition.

While the biology of the clonal plasma cells in AL amyloidosis are distinct from that of MM, a clinical trial was designed by was designed by Vaishali Sanchorawala, MD, et al. with the primary objective of determining the safety and tolerability of infusion of daratumumab in patients with relapsed AL amyloidosis, with respect to infusion reactions (IR).

In addition to the primary endpoints, the investigators also intended to evaluate organ response with respect to cardiac biomarkers and proteinuria, as well as hematologic response and time to next treatment. Enrolled patients will receive daratumumab by IV infusion once weekly for 2 months, then bi-weekly for 4 months, then once each month. Treatment is intended to continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial.

Eight patients were enrolled in the study by the July 23, 2017 data cut-off. Enrolled patients had a median age of 63 years with a range of 60-83, and a median number of 3 prior therapies with a range of 1-6. 75% of patients (n=6) had received HDM/SCT, 62.5% (n=5) had received immunomodulatory agents, and 87.5% (n=7) had received proteosome inhibitors. The median time from diagnosis to enrollment in the trial was 68 months.

As of the data, 65 infusions have been completed and 7 patients continue the study. The median number of infusions received per patient is 9, and only one patient was removed from the protocol after developing progression of plasma cell dyscrasia markers after first infusion. Preliminary data suggest a rapid hematologic response after 1 dose of daratumumab in patients with AL amyloidosis, with 6 patients achieving very good partial response (VGPR).

In November 2015, the drug became the first human anti-CD38 monoclonal antibody approved for treating multiple myeloma, and was approved by the U.S. Food and Drug Administration (FDA) for patients with multiple myeloma who had received 3 prior therapies. A year later, its indication was expanded for patients who had received a minimum of 1 prior therapy.

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Sanchorawala V, Sarosiek S, Thakral N, et al. 507 Safety and Tolerability of Daratumumab in Patients with Relapsed Light Chain (AL) Amyloidosis. Presented at the 59th ASH Annual Meeting & Exposition, December 9-12, 2017; Atlanta GA. Session 653. https://ash.confex.com/ash/2017/webprogram/Paper100472.html

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