1. Stephen Ansell, MD, PhD Mayo Clinic
Watch & Wait is the optimal Management of asymptomatic low-burden Follicular Grade 1/2 Lymphoma Patients
Stephen Ansell, MD, PhD
Mayo Clinic

2. Points to note from the case
Low tumor burden by GELF criteria
Asymptomatic patient – we can’t improve on how the patient feels
Does ‘asymptomatic’ suggest not particularly anxious?
Grade 1-2 follicular lymphoma stage IV is not considered curable with current therapy

3. What are the GELF criteria?

4. What are the goals of therapy for this patient?
Typically the goals in cancer therapy are – cure, improved overall survival, or relief of disease-related symptoms
Issues in this situation – not curable, no evidence that treatment impacts overall survival, patient has no symptoms.
Maybe the goals need to be quality of life, prevention of transformation or complications, or cost?

5. What happens if you adopt a watch and wait policy for asymptomatic advanced-stage Follicular lymphoma?
Time to first systemic treatment for patients in the observation group at 10 years, 19% of patients did not need chemotherapy.
Ardeshna et al. Lancet, Volume 362, Issue 9383, 2003,

6. Long-term effect of watch and wait versus Chlorambucil for asymptomatic advanced-stage Follicular lymphoma
10-year overall survival 34% in observation group and 35% in chlorambucil group.
Ardeshna et al. Lancet, Volume 362, Issue 9383, 2003,

7. Comparison of no therapy versus Prednimustine or Interferon for Low Tumor Burden Follicular lymphoma
Brice et al. JCO March 1997 vol. 15 no

8. Ardeshna et al. Lancet Oncology, Volume 15, Issue 4, 2014, 424 - 435
Rituximab versus watch-and-wait in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: overall survival
Ardeshna et al. Lancet Oncology, Volume 15, Issue 4, 2014,

9. Does a watch-and-wait approach increase the risk of transformation?
Ardeshna et al. Lancet Oncology, Volume 15, Issue 4, 2014,

10. Risk of transformation by initial follicular lymphoma treatment – but overall rate is lower than previously described.
Link B K et al. JCO 2013;31:

11. Is watch and wait really watch and worry?
QOL analysis – at baseline, 7, 12, 24 and 36 months
The negative effect of a diagnosis of lymphoma lessened by month 7 in all groups as patients adjusted to their diagnosis.
At month 7, patients in the maintenance rituximab group were significantly more likely to feel in control of their situation than those in the watchful waiting group.
Patients in the watchful waiting group were significantly more likely to be worrying about the need for treatment than those in the maintenance rituximab group.
However, follow up was mostly by physical exam with rare CT scans, and first treatment was to be chemotherapy (not rituximab).
Ardeshna et al. Lancet Oncology, Volume 15, Issue 4, 2014,

12. Conclusions
Immediate treatment of asymptomatic, low tumor burden patients with advanced follicular lymphoma does not result in cures, improved overall survival or improved symptoms.
Possible benefits in QOL or decreased risk of transformation are questionable.
Cost is significantly increased.
Watch and wait does not mean never treating the patient – it means initiating treatment when it is really needed.
Watch and wait should be the approach of choice in asymptomatic low-burden patients.