While the “eyeball test” is an approximation that requires
individual physician judgment (ie. subject to considerable error), such
measurements have been codified by what we call the “GELF criteria” which is a
French acronym for “groupe d’Etude des lymphomes folliculaires” (ie. French
study group of follicular lymphoma).
You are considered “low tumor burden” provided you lack any
node > 7cm, have less than three nodes areas > 3cm each, no B symptoms
(night sweats, fever, weight loss), spleen below the belly button, circulating
follicular lymphoma, or bone marrow dysfunction from involvement (and a few
others).
The distinction between “low tumor burden” and “high tumor
burden” is relevant because clinical trials often distinguish between such
patients in terms of the appropriateness of certain therapies (see: how I treat follicular lymphoma part 1 and part 2). Patients with “low tumor burden” follicular
lymphoma have been studied in studies such as “rituximab vs watch and wait” or
the Resort trial (how much rituxan alone do you need), or even the SAKK study
(some rituxan vs some plus more rituxan) whereas patients with high tumor
burden are more likely to be studied in chemotherapy type studies such as bendamustine-rituximab
vs R-CHOP type studies or perhaps other new study designs.
I wanted to focus on the “low tumor burden” population
because I was preparing a talk and thought there were a number of important
statistics that such patients should be aware of. I want to simply list them here for your
consideration. They are drawn from three main studies linked here:
Resort Trial (Induction and Maintenance vs Induction and Retreatment when needed)
SAKK Trial (Four doses in one month vs eight doses in nine months)
From the study of “rituximab vs watch and wait”
Approximately 20% of patients with asymptomatic
advanced stage disease can be followed for over 10 years without requiring
treatment
Thus far NO study has shown that starting
treatment EARLIER (ie immediately at diagnosis vs when needed) improves overall
survival (very few studies have ever tried to prove this point
Patients who undergo watchful waiting may
experience spontaneous regression in 12% of patients by two year mark evenly
split between ones that completely disappear from CT scans and ones that
partially disappear (in no case do we think the body has “cured” it, we just
can’t detect it on scan
40% of patients with low tumor burden follicular
lymphoma on watchful waiting will have growth of their lymphoma by two year
mark.
Between 80-90% of patients with low tumor burden
follicular lymphoma who receive rituximab will experience a response when
evaluated several months post treatment
Between 10-30% of patients suitable for watch
and wait yet receive rituximab will experience progression within 24 months
(partially depends on how much rituximab is given)
Despite responses seen following rituximab,
after following patients on average four years after randomization there is no
apparent difference in overall survival or rates of histologic transformation
between patients assigned to watch and wait versus rituximab (perhaps will
change when data more mature?)
The average time a between diagnosis and disease
progression when following watch and wait is approximately two years.
The patients who have most emotionally stable reaction
to their lymphoma are patients who start rituximab and then continue on
maintenance compared to those who take four doses and stop or those on watch
and wait.
From the RESORT study (Rituxan followed by rituxan maintenance
versus four doses or rituxan and rituxan re-use when needed)
In the average patient with low tumor burden
indolent lymphoma who starts rituximab (whether with maintenance or reuse) it
will work for about four years before something new is needed.
Patients who stay on maintenance rituxan are
less likely to have disease progression, but those patients who “reuse” rituxan
are often able to keep the disease under control for about same amount of time
and use less rituxan (about 75% less rituxan)
From the SAKK study (which compared four doses of rituximab
over one month versus eight doses over nine months in both previously treated
and untreated follicular lymphoma)
If you don’t respond initially to rituxan,
continuing it for four more doses doesn’t help
In previously untreated follicular lymphoma
patients who respond to rituxan and get total of eight doses, almost half have
not experienced any progression by 8 years compared to about a quarter of
patients who only get four doses
There is a trend that does not reach the level
of “statistical proof” that any patient with follicular lymphoma who gets eight
doses compared to four might have better overall survival. Caution here – not clear if this is real or
statistical chance just making it look better
Long story short, you can slice and dice this info to do just about anything you want it to mean. In my own practice, I generally start with rituximab once per week for four weeks then give one dose every other month for four more doses if I am starting rituximab alone in previously untreated patients. I would not strenuously argue with others if they did it differently. Here are a few key slides that come from the representative papers as well as a beautiful view of Mt. Washington in the Cascades east of Eugene
Long story short, you can slice and dice this info to do just about anything you want it to mean. In my own practice, I generally start with rituximab once per week for four weeks then give one dose every other month for four more doses if I am starting rituximab alone in previously untreated patients. I would not strenuously argue with others if they did it differently. Here are a few key slides that come from the representative papers as well as a beautiful view of Mt. Washington in the Cascades east of Eugene