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Delineation of the timing of second line therapy post- autologous stem cell transplant in patients with AL amyloidosis

Yi L. Hwa, Rahma Warsame, Morie A. Gertz, Francis K. Buadi, Martha Q. Lacy, Shaji K. Kumar, David Dingli, Steve R. Zeldenrust, Nelson Leung, Suzanne R. Hayman, Prashant Kapoor, Wilson I. Gonsalves, Taxiarchis V. Kourelis, Stephen Russell, Ronald S. Go, Miriam A. Hobbs, Amie L. Fonder, S. Vincent Rajkumar and Angela Dispenzieri

Key points

  • Organ progression at 2nd line therapy predicated inferior survival.

  • Patients relapsing from > VGPR had longer time to develop organ progression.

Abstract

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 re-initiating therapy among 235 patients initially treated with ASCT at Mayo Clinic. The median time from ASCT to second-line therapy was 24.3 months. At the time of restarting therapy, median dFLC was 9.9 mg/dL (42% of diagnosis value); 32% had a dFLC< 5mg/dL; and 63% met criteria for organ R/P. The indications for re-treatment were: 1) clinical suspicion of R/P, 10%; 2) hematologic R/P only, 23%; 3) organ R/P only 32%; 4) both hematologic and organ R/P, 31%; 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 more than 5 mg/dL at the time of reinstituting therapy was associated with risk, patients relapsing from VGPR or better had longer time to develop organ progression after hematologic R/P (24.2 vs 3.2 months, p=0.007). These data suggest that the best candidates for clinical trials testing novel plasma cell directed chemotherapy beyond first line may be those patients who either are relapsing from VGPR or better (dFLC at diagnosis was >5 mg/dL) or are having inadequate response to prior therapy. This strategy should allow for hematologic response assessment whilst avoiding the risk of deleterious organ progression. Implementation of more stringent progression criteria may also be warranted.

  • Submitted May 8, 2017.
  • Accepted July 31, 2017.