Systemic light chain amyloidosis myopathy responsive to daratumumab monotherapy

Abstract

Background and purpose: Amyloid myopathy is a rare and severe manifestation of systemic light chain (AL) amyloidosis. Early diagnosis and staging are mandatory for optimal therapy, given the rapid progression of muscle weakness. Despite the efficacy of bortezomib-based treatment regimens, there is a lack of therapeutic alternatives in non-responsive patients.

Method: The case report of a patient with systemic AL amyloidosis myopathy treated with daratumumab is presented.

Results: A 70-year-old man displayed severe proximal muscle weakness which had developed over a 10-month period. Blood tests revealed an immunoglobulin A lambda monoclonal gammopathy, whilst muscle biopsy showed amyloid deposits within the arteriolar walls, confirming the diagnosis of amyloid myopathy associated with AL amyloidosis. Initial treatment with a bortezomib-based regimen showed no clinical or hematological improvement. After switching to daratumumab monotherapy, our patient achieved a favorable evolution with respect to functional muscle scoring and a complete hematological response.

Conclusion: To our knowledge, this is the first case report of an amyloid myopathy showing a remarkable clinical improvement in response to daratumumab monotherapy. It thereby highlights the potential of daratumumab as a monotherapeutical approach to the treatment of amyloid myopathy complicating AL amyloidosis.

Keywords: amyloid myopathy; daratumumab; light chain amyloidosis; systemic AL amyloidosis.

FIGURE 1

Explorations findings. (a) Whole‐body muscle MRI. Fat imaging of the T2 Dixon axial sequence showing fatty infiltrations with bilateral, symmetrical amyotrophy, predominating in the lower limbs, more severe in the adductors (Mercuri 4), particularly in the left adductor longus (arrow heads), the hamstrings (long arrows), as well as in the medial and lateral soleus and gastrocnemius. The upper limb involvement mainly concerns the shoulder girdle (short arrows) and in particular the rotator cuff (Mercuri 3). The paraspinal muscles are moderately to severely affected (not shown). (b) Muscle biopsy. Congo red staining of a frozen muscle section (left) and Sirius red staining of a paraffin section (right), showing the presence of red material corresponding to amyloid deposits within the endomysial vessels. Note the variation in fiber size and the multiple nuclear internalization in the left panel.

FIGURE 2

Variation of the serum kappa/lambda chain ratio with time over the treatment period. A drastic improvement followed the introduction of daratumumab. CyBorD, cyclophosphamide, bortezomib and dexamethasone