Rare Case of Multiple Myeloma in Patient with Cold Agglutinin Disease Described in Report

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A rare case of a patient with cold agglutinin disease (CAD) who developed a blood cancer called multiple myeloma was recently reported by researchers in Norway.

Although both conditions are linked to malfunctioning of B-cells, in this case, clinicians believe the patient developed the two disorders independent of each other.

The case report, “Development of Multiple Myeloma of the IgA Type in a Patient with Cold Agglutinin Disease: Transformation or Coincidence?” was published in the journal Case Reports in Hematology.

CAD is a chronic autoimmune condition where patients develop autoantibodies that destroy red blood cells causing severe anemia. The autoantibodies are temperature-sensitive, meaning they’re only functional at cold temperatures — below 30 degrees Celsius, or 86 degrees Fahrenheit.

Immune B-cells are responsible for the production of the autoantibodies in CAD, and the disease is actually considered a B-cell disease characterized by an excessive proliferation of these cells.

This uncontrolled division of B-cells is also the underlying cause of blood cancers, namely B-cell lymphomas or multiple myeloma.

However, only 3–4% of CAD cases actually progress to aggressive lymphomas and even more rarely to myeloma, the latter of which has only been reported in a few cases worldwide.

In this report, researchers in Norway described the case of a patient with CAD who also developed multiple myeloma.

The patient, a woman in her late 60s, was admitted to the hospital in 2012 due to anemia that had lasted for more than a year and a half.

Blood tests showed she carried autoantibodies against red blood cells, and she was diagnosed with anemia due to cold agglutinin.

She underwent a bone marrow biopsy, which showed an abnormally high number of immature red blood cells and small clusters of proliferating B-cells, which clinicians suspected was a sign of a type of lymphoma called lymphoplasmacytic lymphoma.

A second bone marrow biopsy performed in 2014 showed white blood cells (another group of immune cells) infiltrates, suggestive of lymphoplasmacytic lymphoma caused by CAD.

She remained stable until 2016 when her condition deteriorated. She was given Rituxan (rituximab), an engineered antibody developed by Roche to specifically target the cell surface protein CD20 often found in B-cells.

However, despite the treatment, the levels of autoantibodies increased in the blood and that of hemoglobin decreased, a sign that red blood cells were continuing to be destroyed. At this time, the patient experienced severe low back pain after exposure to cold and hard work, in this case, removing snow from a courtyard.

A new bone marrow biopsy revealed an infiltration of a group of B-cells, which accounted for 20% of the cells, and the patient was diagnosed with multiple myeloma, a blood cancer that develops in the bone marrow and occurs when a plasma cell, a type of cell in the soft center of bone marrow, becomes cancerous and starts to proliferate uncontrollably.

In March 2018, the patient was treated with bortezomib, an anti-cancer therapy sold under the brand name Velcade among others, which improved hemoglobin levels and led to multiple myeloma remission.

The team questioned whether the development of multiple myeloma was linked to the patient’s CAD or if the cancer was a coincidence.

They ultimately concluded that the two disorders were not connected, deeming it unlikely that the B-cells responsible for CAD caused the malignancy, since the autoantibodies remained high even after treatment with Rituxan.

“Both CAD and MM [multiple myeloma] responded well to bortezomib-based combination therapy, which is an established treatment option in MM,” they said.