TY - JOUR
T1 - Delineation of the timing of second-line therapy post–autologous stem cell transplant in patients with AL amyloidosis
AU - Hwa, Yi L.
AU - Warsame, Rahma
AU - Gertz, Morie A.
AU - Buadi, Francis K.
AU - Lacy, Martha Q.
AU - Kumar, Shaji K.
AU - Dingli, David
AU - Zeldenrust, Steve R.
AU - Leung, Nelson
AU - Hayman, Susanne R.
AU - Kapoor, Prashant
AU - Gonsalves, Wilson I.
AU - Kourelis, Taxiarchis V.
AU - Russell, Stephen
AU - Go, Ronald S.
AU - Hobbs, Miriam A.
AU - Fonder, Amie L.
AU - Rajkumar, S. Vincent
AU - Dispenzieri, Angela
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/9/28
Y1 - 2017/9/28
N2 - Among patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur. We conducted a retrospective study to evaluate the patterns of relapse or progression (R/P) and the timing of reinitiating therapy among 235 patients initially treated with autologous stem cell transplant (ASCT) at Mayo Clinic. The median time from ASCT to second-line therapy was 24.3 months. At the time of restarting therapy, median difference of free light chain (dFLC) was 9.9 mg/dL (42% of diagnosis value), 32% had a dFLC <5 mg/dL, and 63% met criteria for organ R/P. The indications for retreatment were (1) clinical suspicion of R/P, 10%; 92) hematologic R/P only, 23%; (3) organ R/P only, 32%; (4) both hematologic and organ R/P, 31%; and (5) suboptimal response to ASCT and second-line therapy as consolidation, 4%. Patients with organ progression at the time of second-line therapy had inferior survival. Although a dFLC of >5 mg/dL at the time of reinstituting therapy was associated with risk, patients relapsing from very good partial response (VGPR) or better had a longer time to develop organ progression after hematologic R/P (24.2 vs 3.2 months, P 5 .007). These data suggest that the best candidates for clinical trials testing novel plasma cell–directed chemotherapy beyond first line may be those patients who are either relapsing from VGPR or better (dFLC at diagnosis was >5 mg/dL) or having inadequate response to prior therapy. This strategy should allow for hematologic response assessment while avoiding the risk of deleterious organ progression. Implementation of more stringent progression criteria may also be warranted.
AB - Among patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur. We conducted a retrospective study to evaluate the patterns of relapse or progression (R/P) and the timing of reinitiating therapy among 235 patients initially treated with autologous stem cell transplant (ASCT) at Mayo Clinic. The median time from ASCT to second-line therapy was 24.3 months. At the time of restarting therapy, median difference of free light chain (dFLC) was 9.9 mg/dL (42% of diagnosis value), 32% had a dFLC <5 mg/dL, and 63% met criteria for organ R/P. The indications for retreatment were (1) clinical suspicion of R/P, 10%; 92) hematologic R/P only, 23%; (3) organ R/P only, 32%; (4) both hematologic and organ R/P, 31%; and (5) suboptimal response to ASCT and second-line therapy as consolidation, 4%. Patients with organ progression at the time of second-line therapy had inferior survival. Although a dFLC of >5 mg/dL at the time of reinstituting therapy was associated with risk, patients relapsing from very good partial response (VGPR) or better had a longer time to develop organ progression after hematologic R/P (24.2 vs 3.2 months, P 5 .007). These data suggest that the best candidates for clinical trials testing novel plasma cell–directed chemotherapy beyond first line may be those patients who are either relapsing from VGPR or better (dFLC at diagnosis was >5 mg/dL) or having inadequate response to prior therapy. This strategy should allow for hematologic response assessment while avoiding the risk of deleterious organ progression. Implementation of more stringent progression criteria may also be warranted.
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U2 - 10.1182/blood-2017-05-783415
DO - 10.1182/blood-2017-05-783415
M3 - Article
C2 - 28807981
AN - SCOPUS:85030032278
SN - 0006-4971
VL - 130
SP - 1578
EP - 1584
JO - Blood
JF - Blood
IS - 13
ER -