Treatment responses remain poor in IgM light-chain amyloidosis

Last Updated: 2016-04-27

By Will Boggs MD

NEW YORK (Reuters Health) - Only about one in seven patients with immunoglobulin M (IgM)-related light chain amyloidosis show complete or very good partial responses to treatment, researchers report.

"IgM amyloidosis is different from AL in general," Dr. Ashutosh D. Wechalekar, from University College London Medical School, UK, told Reuters Health by email. "I hope this report will encourage physicians to use appropriate hematopathology to confirm the underlying clonal diagnosis, help them to risk-stratify these patients using the new model, and consider appropriate therapies to the underlying bone marrow pathology."

Until now, IgM amyloid light-chain (AL) amyloidosis has been classified with other forms of amyloidosis, although some have suggested that its clinical features distinguish it from non-IgM AL amyloidosis.

Dr. Wechalekar's team reported the utility of prognostic and response criteria in a series of 250 patients with IgM AL amyloidosis, as well as the clinical characteristics and outcomes of these patients.

Tissue involvement included the heart in 45%, the kidney in 68%, soft tissue in 35%, and the liver in 17% of patients, according to the April 25 Journal of Clinical Oncology report.

Most patients (52%) had a clearly identified lymphoproliferative disorder, and in nearly a third of these patients its diagnosis predated the diagnosis of AL amyloidosis.

Patients were treated with 22 different combinations used as first-line therapy. Rituximab in combination with bortezomib or combination chemotherapy was the most frequent regimen since 2010.

Although 57% of treated patients achieved a hematologic response, only 9% had a very good partial response (VGPR) and only 5% had a complete response.

Median overall survival was 47.9 months and was better in patients with no identifiable clonal infiltrate in the bone marrow (54 months) than in those who had lymphoid infiltrate (44 months) or plasma cell-predominant infiltrate (23 months).

Multivariate analysis allowed the creation of a new risk model that incorporates N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T, liver involvement, and presence of neuropathy. Increasing numbers of abnormalities in these factors are associated with declining median survival.

"Thus far, we have focused on cardiac disease," Dr. Wechalekar said. "This model alerts us to the fact the neuropathic disease in context of IgM is equally important."

Organ response rates in these patients (cardiac 5%, liver 27%, and renal 18%) were much lower than those reported among IgA and/or IgG AL amyloidosis patients.

"The goal of therapy in AL amyloidosis is generally a VGPR or better," Dr. Wechalekar concluded. "In patients with neuropathy, there is now all the more reason to use agents that will lead to a VGPR or better - and switching therapies to reach this goal is important."

"Currently, autologous stem-cell transplantation and bortezomib-based treatment regimens seem to be associated with best responses, although the prolonged time to next treatment seen with fludarabine, cyclophosphamide, and rituximab raises the important issue of accurately targeting the lymphoid component of the clone for longer term disease control," the researchers noted. "Novel targeted therapies need to be further explored in this condition."

"An international tissue and data registry would help to broaden the understanding of IgM-related AL amyloidosis," they added.

Dr. Vaishali Sanchorawala, director of Boston Medical Center's Autologous Stem Cell Transplant Program, told Reuters Health by email that the proposed risk model is "too complicated and useless, as all patients do require treatment and none is indolent not requiring treatment."

"Survival, as with other types of amyloidosis, is related to deep hematologic responses and absence of cardiac involvement," Dr. Sanchorawala said.

The authors reported no funding. Eight coauthors reported disclosures.

SOURCE: http://bit.ly/1YUeZIm

J Clin Oncol 2016.