Conventional Therapy for Amyloid Light-Chain Amyloidosis

Abstract

The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional regimens are based on various combinations of dexamethasone, alkylating agents, proteasome inhibitors, and immunomodulatory drugs. The choice of these regimens requires a careful risk stratification, based on the extent of amyloid organ involvement, comorbidities, and the characteristics of the amyloidogenic plasma cell clone. Most patients are treated upfront with bortezomib and dexamethasone combined with cyclophosphamide or melphalan. Cyclophosphamide does not compromise stem cell mobilization and harvest and is more manageable in renal failure. Melphalan can overcome the effect of t(11; 14), which is associated with lower response rates and shorter survival in subjects treated with bortezomib and dexamethasone, or in combination with cyclophosphamide. Lenalidomide and pomalidomide are the mainstay of rescue treatment. They are effective in patients exposed to bortezomib, dexamethasone, and alkylators, but deep hematologic responses are rare. Ixazomib, alone or in combination with lenalidomide, increases the rate of complete responses in relapsed/refractory patients. Conventional chemotherapy regimens will represent the backbone for future combinations, particularly with anti-plasma-cell immunotherapy, that will further improve response rates and outcomes.

Periorbitalis bőrtünetekkel járó könnyűlánc-amyloidosis

“…A kórlefolyást leginkább a cardialis érintettség, valamint a társuló plazmasejt-proliferációs betegség súlyossága determinálja. Kezelésére jelenleg a bortezomib, a dexametazon és alkilálószerek kombinációja a standard elfogadott terápia [11]. A közeljövőben plazmasejtellenes immunterápia, elsősorban a daratumumab is belekerülhet a terápiás ajánlásokba, valamint ígéretes vizsgálatok folynak egyéb, plazmasejtellenes immunterápiákkal is (elotuzumab, sziltuximab, izatuximab).…”

“…A doxiciklin in vitro vizsgálatban az amyloidfibrillumokat bontotta, és az amyloidterhelés csökkenését eredményezte [12]. Egy retrospektív esettanulmány szerint a doxiciklinnel kiegészített hagyományos kemoterápiás kezelés javította a cardialis érintettséggel járó könnyűlánc-amyloidosisban szenvedő betegek átlagos túlélését [11]. A napjainkban elérhető korszerű terápiával akár 5 év feletti túlélés is elérhető [13].…”

Lenalidomide and dexamethasone in relapsed/refractory immunoglobulin light chain (AL) amyloidosis: results from a large cohort of patients with long follow‐up

“…Immunomodulatory imide drugs (IMiDs) represent the backbone of rescue treatment. 2,3 Lenalidomide and dexamethasone (RD) is considered a standard treatment for relapsed/refractory AL amyloidosis (RRAL). The effectiveness of this regimen was first documented in two small clinical trials, even though the maximum tolerated dose of lenalidomide was only 15 mg/day.…”

“…Bortezomib‐based regimens and autologous stem cell transplant (ASCT) in selected patients are the cornerstone of first‐line therapy. Immunomodulatory imide drugs (IMiDs) represent the backbone of rescue treatment 2,3 …”

Worldwide Perspectives of Amyloidosis

“…Anti-plasma cell-directed therapy is comprised of nonchemotherapy treatment, conventional chemotherapy, and autologous stem cell transplantation. Milani and Palladini [7] supplies us with a very well-organized review on the value of conventional therapy in amyloidosis. The readers will also enjoy the review of Van Doren and Lentzsch [8], which leads us through nonchemotherapy treatments of amyloidosis and presents data on the current standard of care, VCd, as well as emerging evidence of the important role of daratumumab [9][10][11][12], which may define the new standard of care [13].…”