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Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet?

Abstract
Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5- and 10-year PFS rates are ~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.
AuthorsN Epperla, T S Fenske, H M Lazarus, M Hamadani
JournalBone marrow transplantation (Bone Marrow Transplant) Vol. 50 Issue 11 Pg. 1393-404 (Nov 2015) ISSN: 1476-5365 [Electronic] England
PMID26281033 (Publication Type: Journal Article, Review)
Chemical References
  • Antibodies, Monoclonal
  • Histone Deacetylase Inhibitors
  • Immunotoxins
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Protein Kinase Inhibitors
  • Rituximab
  • Protein-Tyrosine Kinases
Topics
  • Antibodies, Monoclonal (therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Disease-Free Survival
  • Forecasting
  • Genes, cdc
  • Hematopoietic Stem Cell Transplantation
  • Histone Deacetylase Inhibitors (administration & dosage)
  • Humans
  • Immunotherapy
  • Immunotoxins (therapeutic use)
  • Lymphoma (drug therapy, therapy)
  • Maintenance Chemotherapy
  • Molecular Targeted Therapy
  • Neoplasm Proteins (antagonists & inhibitors, immunology)
  • Programmed Cell Death 1 Receptor (antagonists & inhibitors, immunology)
  • Protein Kinase Inhibitors (administration & dosage)
  • Protein-Tyrosine Kinases (antagonists & inhibitors, immunology)
  • Randomized Controlled Trials as Topic
  • Rituximab (administration & dosage)
  • Signal Transduction (drug effects)
  • Survival Rate
  • Transplantation, Autologous
  • Treatment Outcome

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