2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

will go straight to maintenance. All three arms will receive
lenalidomide maintenance for 3 years or until disease progression
(Fig. 3).
Immunotherapy
The post-transplant period is the ideal time point for
immunotherapy, as theoretically the disease burden is low.
Immune function remains depressed post-high-dose therapy
for many months. Ex vivo expansion and subsequent transfer
of autologous stimulated T cells may enhance host
antitumor immunity and may also allow for enhancement
of a post-transplant vaccination strategy against tumordirected
antigens. A phase I/II trial of this strategy in 54
patients has been conducted. 27 At day 2, patients who were
post-transplant received an infusion of ex vivo stimulated
antiCD3/antiCD28 T cells. Patients positive for HLA-A2
antigen received pneumococcal vaccination and a multipeptide
tumor antigen vaccine. Patients who were negative
received the pneumococcal vaccine only. Significant T-cell
recovery was seen at day 14. A subset of patients developed
immune responses to tumor antigens, but this did not
Author’s Disclosure of Potential Conflicts of Interest
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translate into improved EFS. However, the potential of this
approach is suggested by the demonstration of the rapid
recovery of cellular and humoral immunity as well as
immune responses to the cancer vaccine. Future trials will
focus on vaccines for other possibly more potent tumor
antigens and the use of adjuvant therapy, such as immunomodulatory
agents, in conjunction with T-cell infusions.
Conclusion
Where does this leave the treating physician in 2012 as he
or she eyes the future? This future will likely include a more
risk-adapted approach, with risk stratification determined
by clinical features, cytogenetics, and GEP. The goal of
therapy would be to minimize toxicity in the patient with
low-risk disease and minimize risk of relapse in the patient
with poor-risk disease. Post-transplant disease assessment
by detection of minimal residual disease may also help guide
therapy. Options would include post-transplant consolidation
with either current or new agents, reduced intensity
allogeneic transplant, NK- or T-cell-directed immunotherapy,
and long-term maintenance with new agents.
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Ownership Honoraria
Amrita Krishnan Merck Celgene Celgene;
Genentech;
Millennium
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