TY - JOUR
T1 - Organ responses with daratumumab therapy in previously treated AL amyloidosis
AU - Chung, Alfred
AU - Kaufman, Gregory P.
AU - Sidana, Surbhi
AU - Eckhert, Erik
AU - Schrier, Stanley L.
AU - Lafayette, Richard A.
AU - Arai, Sally
AU - Witteles, Ronald M.
AU - Liedtke, Michaela
N1 - Funding Information:
Conflict-of-interest disclosure: G.P.K. has received travel, lodging, and meal reimbursement, as well as research support, from Janssen. M.L. has acted as a consultant for Adaptive, Amgen/Onyx, and IQVIA/Jazz pharmaceuticals; has received research funding from Agios, Amgen/Onyx, bluebird bio, Caelum, Celator Pharmaceuticals, Celgene, Genentech/Roche, Gilead, Janssen, Novartis, Pfizer, Prothena, and Takeda; has received honoraria from Amgen/ Onyx, Caelum, Pfizer, and Prothena; and has served on advisory committees for Caelum, Gilead, Pfizer, Prothena, and Takeda. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/2/11
Y1 - 2020/2/11
N2 - Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking. Seventy-two patients with previously treated AL amyloidosis who received daratumumab monotherapy with dexamethasone were retrospectively evaluated. With a median follow-up of 27 months, 2-year overall survival (OS) was 86.9% (median OS, not reached) and 2-year time-to-next treatment or death (TTNT)-free survival was 62% (median TTNT, not reached). Forty of 52 evaluable patients achieved a hematologic response (77%), with >60% of patients achieving a very good partial response or better; median time-to-hematologic response was 1 month. Fifty-seven patients (79%) had cardiac involvement, and 55% of evaluable patients achieved a cardiac response, with a median response time of 3.2 months among responders. Cardiac responses were associated with an improvement in OS, with landmark analysis for cardiac responses at 3 months trending toward statistical significance (100% vs 55% at 30 months, P =.051). Forty-seven patients (65%) had renal involvement, and 52% of evaluable patients achieved a renal response, with a median response time of 6 months among responders; there was no significant difference in OS between renal responders and nonresponders. This study demonstrates that daratumumab is highly effective in the treatment of previously treated AL amyloidosis, and a significant proportion of patients can achieve deep hematologic responses, as well as improvements in organ function.
AB - Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking. Seventy-two patients with previously treated AL amyloidosis who received daratumumab monotherapy with dexamethasone were retrospectively evaluated. With a median follow-up of 27 months, 2-year overall survival (OS) was 86.9% (median OS, not reached) and 2-year time-to-next treatment or death (TTNT)-free survival was 62% (median TTNT, not reached). Forty of 52 evaluable patients achieved a hematologic response (77%), with >60% of patients achieving a very good partial response or better; median time-to-hematologic response was 1 month. Fifty-seven patients (79%) had cardiac involvement, and 55% of evaluable patients achieved a cardiac response, with a median response time of 3.2 months among responders. Cardiac responses were associated with an improvement in OS, with landmark analysis for cardiac responses at 3 months trending toward statistical significance (100% vs 55% at 30 months, P =.051). Forty-seven patients (65%) had renal involvement, and 52% of evaluable patients achieved a renal response, with a median response time of 6 months among responders; there was no significant difference in OS between renal responders and nonresponders. This study demonstrates that daratumumab is highly effective in the treatment of previously treated AL amyloidosis, and a significant proportion of patients can achieve deep hematologic responses, as well as improvements in organ function.
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U2 - 10.1182/bloodadvances.2019000776
DO - 10.1182/bloodadvances.2019000776
M3 - Article
C2 - 32027745
AN - SCOPUS:85082185668
SN - 2473-9529
VL - 4
SP - 458
EP - 466
JO - Blood Advances
JF - Blood Advances
IS - 3
ER -