TY - JOUR
T1 - Long-term outcomes of IMiD-based trials in patients with immunoglobulin light-chain amyloidosis
T2 - a pooled analysis
AU - Warsame, Rahma
AU - LaPlant, Betsy
AU - Kumar, Shaji K.
AU - Laumann, Kristina
AU - Perez Burbano, Gabriela
AU - Buadi, Francis K.
AU - Gertz, Morie A.
AU - Kyle, Robert A.
AU - Lacy, Martha Q.
AU - Dingli, David
AU - Leung, Nelson
AU - Hayman, Suzanne R.
AU - Kapoor, Prashant
AU - Hwa, Yi L.
AU - Fonder, Amie
AU - Hobbs, Miriam
AU - Gonsalves, Wilson I.
AU - Kourelis, Taxiarchis
AU - Lust, John
AU - Russell, Stephen J.
AU - Zeldenrust, Steven
AU - Lin, Yi
AU - Muchtar, Eli
AU - Go, Ronald S.
AU - Vincent Rajkumar, S.
AU - Dispenzieri, Angela
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Rarity of light-chain amyloidosis (AL) makes randomized studies challenging. We pooled three phase II studies of immunomodulatory drugs (IMiDs) to update survival, toxicity, and assess new response/progression criteria. Studies included were lenalidomide-dexamethasone (Len-Dex) (n = 37; years: 2004–2006), cyclophosphamide-Len-Dex (n = 35; years: 2007–2008), and pomalidomide-Dex (n = 29; years: 2008–2010) trial. Primary endpoint was hematologic response. Overall survival (OS) was calculated from registration to death and progression-free survival (PFS) was calculated from registration to progression or death. Hematologic, cardiac, and renal response/progression was assessed using the modern criteria. Analysis included 101 patients, with a median age of 65 years, 61% male, 37 newly diagnosed (ND), and 64 relapsed/refractory (RR). Median follow-up was 101 months (range 17–150) and 78% of patients died. OS and PFS for pooled cohort were 31 and 15 months, respectively. Forty-eight patients achieved a hematologic response; for ND, 10 patients (28%) achieved ≥VGPR (very good partial response) and 8 (14%) among the RR. Only cardiac stage was prognostic for OS. Common grade ≥3 toxicities were hematologic, fatigue, and rash, and were similar among studies. Hematologic and renal responses occurred more frequently and rapidly using modern response criteria; cardiac response was less frequent but occurred quickly. IMiDs can result in long progression-free intervals/survival with tolerable toxicities. The new response/progression criteria were rapid and allows for tailoring therapy.
AB - Rarity of light-chain amyloidosis (AL) makes randomized studies challenging. We pooled three phase II studies of immunomodulatory drugs (IMiDs) to update survival, toxicity, and assess new response/progression criteria. Studies included were lenalidomide-dexamethasone (Len-Dex) (n = 37; years: 2004–2006), cyclophosphamide-Len-Dex (n = 35; years: 2007–2008), and pomalidomide-Dex (n = 29; years: 2008–2010) trial. Primary endpoint was hematologic response. Overall survival (OS) was calculated from registration to death and progression-free survival (PFS) was calculated from registration to progression or death. Hematologic, cardiac, and renal response/progression was assessed using the modern criteria. Analysis included 101 patients, with a median age of 65 years, 61% male, 37 newly diagnosed (ND), and 64 relapsed/refractory (RR). Median follow-up was 101 months (range 17–150) and 78% of patients died. OS and PFS for pooled cohort were 31 and 15 months, respectively. Forty-eight patients achieved a hematologic response; for ND, 10 patients (28%) achieved ≥VGPR (very good partial response) and 8 (14%) among the RR. Only cardiac stage was prognostic for OS. Common grade ≥3 toxicities were hematologic, fatigue, and rash, and were similar among studies. Hematologic and renal responses occurred more frequently and rapidly using modern response criteria; cardiac response was less frequent but occurred quickly. IMiDs can result in long progression-free intervals/survival with tolerable toxicities. The new response/progression criteria were rapid and allows for tailoring therapy.
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U2 - 10.1038/s41408-019-0266-9
DO - 10.1038/s41408-019-0266-9
M3 - Article
C2 - 31913261
AN - SCOPUS:85077637384
SN - 2044-5385
VL - 10
JO - Blood cancer journal
JF - Blood cancer journal
IS - 1
M1 - 4
ER -