The document discusses the role of maintenance therapy in lymphoma treatment, focusing on its purpose of maintaining remission and improving survival with minimal toxicity. It evaluates various drugs used for maintenance therapy, such as chlorambucil, interferon, and rituximab, detailing their effectiveness, side effects, and current applications. Future directions in maintenance therapy are explored, with an emphasis on emerging drugs and their potential benefits.

1. The Role of Maintenance Therapy
in Lymphoma
Arnie Freedman, M.D.
Clinical Director, Dana-Farber/Brigham and Women’s
Cancer Center Adult Lymphoma Program

2. Maintenance
the process of maintaining or
preserving someone or something,
or the state of being maintained.
synonyms: preservation,
conservation, keeping,
prolongation, perpetuation, carry
on, continuation.

3. Maintenance therapy for lymphoma
Use an effective therapy after remission is
attained, to maintain that remission and
hopefully increase survival, without increased
toxicity, both early and late.

4. Maintenance therapy
What is the goal ?
maintaining remission
improving survival
What disease ?
What drug to use ?

5. Maintenance therapy
What are the endpoints and what disease ?
(goals: remission, survival, both)
For aggressive disease, remission and
survival easier to demonstrate.
For indolent disease, survival benefit
harder to prove.

6. Maintenance therapy
What drug to use ?
has to be effective by itself against
the disease.
benefits have to outweigh the side
effects and risks.

7. Drug choices
Has anyone taken chlorambucil for long time?
Chemotherapy (chlorambucil)
Pros
effective agent, convenient (oral), no hair
loss, minimal nausea.
Cons:
lowers blood counts, toxic to stem cells,
risk of malignancy (solid tumor, leukemia).

8. Drug choices
Has anyone taken interferon ?
Interferon-a
Pros
“immunotherapy”
Cons:
minimal anti-lymphoma activity, some
inconvenience (inject), flu like symptoms

9. Drug choices
Raise your hand if you have had rituximab
maintenance ?
Rituximab
Pros
effective agent, some inconvenience (I.V.)
Cons:
infusion reactions, infection risk

10. Maintenance studies (randomized)
Past
CLL, follicular NHL (chemotherapy,
interferon)
Present
DLBCL, follicular NHL, MCL (rituximab)
Future
DLBCL, Hodgkin’s, others (small
molecules, antibody-drug conjugates)

11. Maintenance: the past
Chlorambucil maintenance for CLL
No advantage in survival
Myelosuppression
More second malignancies
(AML/MDS/solid tumors)

12. Maintenance: the past
Interferon maintenance for follicular NHL
Chemotherapy followed by maintenance
or none.
Longer remissions, no advantage in
survival.
Poor tolerance, compliance.
Never adopted in U.S.A.

13. Maintenance: the present
Rituximab maintenance for follicular NHL
Longer remissions after chemotherapy,
chemoimmunotherapy, rituximab alone.
No increased survival (yet).
Reasonably well tolerated, increased viral
infections.
Well adopted in U.S.A.

14. Maintenance: the present
Rituximab maintenance for DLBCL, MCL.
For MCL but not DLBCL, longer
remissions after chemoimmunotherapy.
Improved survival for MCL.
Well tolerated, but maintenance is
indefinite (MCL study).

15. Maintenance: the future
Should maintenance be pursued?
Generally has not worked well (rituximab is the
exception).
Wrong drug choice, wrong disease, hard to
study (compliance and safety).
Will new effective drugs work as maintenance?
ADC (brentuximab), oral kinase inhibitors

16. Maintenance: the future
Enzastaurin (oral kinase inhibitor)
Maintenance for DLBCL
No benefit
Marginally effective drug
Induction prior to maintenance more
effective than in past.

17. Maintenance: the future
Brentuximab (antibody drug conjugate)
Maintenance for Hodgkin lymphoma post
autoSCT.
Oral kinase inhibitors being studied
for example, idelalisib for follicular NHL