Clinical Features and Treatment Response of Light Chain (AL) Amyloidosis Diagnosed in Patients with Previous Diagnosis of Multiple Myeloma (MM).

Both multiple myeloma (MM) and (AL) amyloidosis are clonal plasma cell proliferative disorders. While AL rarely “progresses” to MM, probably due to the shorter survival of AL patients, patients with MM have been reported to develop overt AL at a higher frequency. We conducted this study to identify and describe the clinical features, diagnosis, treatment patterns and response, and outcome among patients diagnosed with AL following an initial diagnosis of MM.

Of the 354 patients identified from a prospectively maintained database who carried a diagnosis of both MM and AL during the interval between January 1990 and December 2008, 44 patients had a histologic diagnosis of AL, at least 6 months after the diagnosis of MM. The organ involvement and treatment response (organ and hematologic) for AL as well as MM response to treatment were assessed according to conventional criteria.

The median age at diagnosis of MM and AL was 63 years (range, 42-82) and 68 years (range, 45-86), respectively; 27 (61%) were males. The median time to AL diagnosis after MM diagnosis was 41 months (range, 7.6-134). The estimated median follow up from diagnosis of MM and AL is 15.5 years and 10 years, respectively and 39 (89%) patients have died. The median overall survival (OS) from diagnosis of MM and AL was 68.6 months and 9.1 months, respectively. At the time of AL diagnosis, 33 (75%) patients had developed typical features suggestive of AL [heart failure (12), paresthesias (11), nephrotic range proteinuria (9), elevated alkaline phosphatase and hepatomegaly (2), fatigue (7), weight loss (5), macroglossia (4) and periorbital ecchymoses (1)]; while others developed atypical features (3) (7%) or had an incidental finding of AL (8) (18%) [autopsy (2), unexplained cytopenia (2), mild proteinuria (1) and no symptoms (3)]. Cumulatively, amyloid deposits were revealed by biopsy of: bone marrow (23) (52%), subcutaneous abdominal fat (17) (39%), organ (10) (23%) and carpal tunnel tissue (6) (14%). Organ involvement, treatment response and hematologic status of MM at AL diagnosis were assessed for the evaluable patients. None, 1 and >1 organ involvement occurred in 5 (11%), 28 (64%) and 9 (20%) patients, respectively at AL diagnosis or follow up; while AL as the cause of neuropathy was questionable in 2. The organs involved were: heart (14, including 8 with >1 organ involvement), nerves (11), kidney (10), soft tissue (6), lung (5), GI (1) and liver (1). The hematologic status of MM at AL diagnosis included SD (22), progression (10), PR (3), VGPR (3) and not evaluable (6). The subsequent hematologic and organ response did not differ significantly among those who had a treatment change or started (20) (45%) compared with those who did not have a treatment change (20) (45%) at AL diagnosis [excluding those lost to follow up (2) or diagnosed at autopsy (2)]; although more patients (8/10) who had biochemically progressive MM belonged to the former group. The best hematologic response to treatment(s) after AL diagnosis (28) (64%) was: SD (17), PR (3), VGPR (6), CR (1), and progression (1); and not evaluable in others. The organ response (excluding patients with carpal tunnel surgery) to treatment(s) (18) (41%) was: progression (11), stable (4) and organ improvement (3). More patients with an improved (2/3) and stable (1/4) organ response had hematologic PR or better than those with progression (0/11) of organ disease. Five (11%) patients were alive at last follow up; and had either isolated kidney (3) and soft tissue (macroglossia) (1) or no organ involvement (1). All patients with an organ improvement, and 2/5 patients alive, had received PBSCT after AL diagnosis. Fewer patients with >1 organ involvement (1/9) underwent PBSCT compared with those without organ involvement (2/5); and achieved (0) PR versus (3) VGPR (to any treatment), respectively. Only 1/8 patient with an incidental discovery of AL developed symptomatic (cardiac) AL after 108 months of MM diagnosis and died; the remaining are either alive (1) or died from MM and its complications (3), infection (1), or were diagnosed at autopsy (2).

The recognition of AL (especially cardiac and multiorgan involvement) is critical in MM patients in order to determine prognosis and influence treatment. A high index of suspicion is required for the prompt recognition of AL to ensure timely institution of therapy with a goal of achieving hematologic and organ response.

No relevant conflicts of interest to declare.