NcXHF

MANAGEMENT OF DLBCL BASED ON MOLECULAR PROFILE
cantly change clinical outcomes. This may likely be a result of
the inherent rapid tumor cell growth and inherent drugresistant
DHL cells that remain after induction therapy (i.e.,
minimal residual disease) that would likely not be cured with a
high-dose, chemotherapy-based conditioning regimen typically
utilized during autologous stem cell transplantation. Of interest,
review of the literature identifıed two abstracts, which included
a total of approximately 50 patients, that concluded that patients
with DHL who undergo allogeneic SCT following doseintensive
induction therapy have prolonged OS. 57,59 Unfortunately,
several reasons make it unlikely that allogeneic SCT will
make a major effect in the future treatment of a signifıcant percentage
of DHL patients: (1) limited data from a small number
of selected patients, (2) the risk of relapsed disease while awaiting
graft-versus-lymphoma to occur, (3) the need for a suitable
HLA-compatible donor, and (4) the risk of chronic graft-versushost
disease.
The future holds promise that novel targeted agents, which
either directly or indirectly inhibit MYC and BCL2, will lead
to improved overall survival in patients with DHL (Table 3).
Many agents have demonstrated in vitro and in vivo animal antitumor
activity, and a limited number are in early human clinical
trials. It is quite likely that DHL will require a rational
combination of MYC/BCL2 inhibitors in combination with effective
chemotherapeutic agents (e.g., BH 3 -mimetics will resensitize
cells to drug toxicity, etc.) to optimize the killing of these
highly resistant lymphoma cells and change DHL from one of
the worst subtypes of DLBCL into a therapeutically responsive
subtype (with a signifıcant improvement in clinical outcomes).
Based on the information provided above, all newly diagnosed
DLBCL tumor biopsies should undergo FISH and IHC evaluation
to identify DHL and DEL, respectively. These patients,
whenever possible, should be referred to participation on clinical
trials. Off study, the use of R-EPOCH induction (including
central nervous system prophylaxis) is a reasonable approach
while we await further testing and validation of effective novel
targeted agents to be added to our current therapeutic armamentarium
against DHL.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: Myron S. Czuczman, Algeta, Boehringer
Ingelheim, Celgene, Gilead Sciences, Mundipharma, T G Therapeutics, Teva. Consulting or Advisory Role: Myron S. Czuczman, Algeta, Boehringer Ingelheim,
Celgene, Gilead Sciences, Mundipharma, T G Therapeutics, Teva. Grzegorz S. Nowakowski, Celgene, Morphosis. Speakers’ Bureau: None. Research Funding:
Grzegorz S. Nowakowski, Celgene (Inst). Patents, Royalties, or Other Intellectual Property: None. Expert Testimony: None. Travel, Accommodations,
Expenses: None. Other Relationships: None.
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