Is w&w passe'? - Leonard vs. Czuczman

[Guest guest]

L & M Conference debate: Is w & w passe'? - Leonard vs. Czuczman

It seemed that the debate question was asked in order to frame and explore

the many issues surrounding Follicular lymphoma (and likely other indolent

lymphomas) in respect to when to treat and with what - and how and when

patient preferences can play a role.

In short, I came away thinking that both experts agreed that:

1) Watch and wait (w & W) is NOT passe'

2) But that it's NOT wise to wait until the patient is sick (symptomatic)

before treating

While not officially agreed upon, I expect both experts would agree with Dr.

Leonard's point that the determination of the need to treat is very

subjective and often based on unreliable estimates of disease status and

behavior.

On point 2, the implication for me was that being symptomatic is often an

indication of having rapidly advancing or bulky disease (a disease status

that exceeds the standard criteria of when to treat), which can be more

challenging to treat effectively and can limit therapy options.

Dr. Leonard also noted -- in support of w & w -- that there are reported cases

of patients never requiring treatment, and that the average time to having

need to treat is about 3 years based on a few single center studies

(specific to follicular lymphoma) that measured this.

Dr. Leonard then made the case for upfront Rituxan as an appropriate first

therapy - in asymptomatic untreated FL ... which I think is a separate

question (what to use first) - but related to the debate question in that

this approach is arguably more reasonable (more likely to be effective) if

you use it earlier - before the FL gets too advanced and before you are

symptomatic.

So in the debate Leonard provided a case-based rationale for treating

earlier than one might otherwise with Rituxan monotherapy the patient who

has not yet met all of the accepted criteria for having a need to treat by

standard criteria. He gave the example of the patient who has significant

anxiety about the disease (impairing his quality of life) and who wants also

to delay or hopefully avoid using chemotherapy.

==

Czuczman made the case that w & w is NOT passe'

He noted that w & w is accepted world-wide as the standard of care based on

the many standard criteria (such as GELF, BLNI, and NCCN) published to help

guide clinicians but also to standardize enrollment for clinical trials.

He then cited the lack of evidence to show any survival benefit from

treating early and noted the benefit of avoiding toxic therapy until there

is a need to treat, and the potential for becoming refractory to agents that

may be need later.

On the early use of Rituxan trial (Adeshna), he noted that there is no OS

advantage, no optimal treatment schedule defined, he cited the associated

costs and time requirement, the infectious risks (probably small, but real),

and that the potential impact on responsiveness to second line therapy is

unknown, and that it's also unknown if maintenance is better than waiting

until the need to treat with Rituxan.

Czuczman provided the factors that treatments are based on:

* Stage and bulk

* FLIPI index

* Transformation

* Sites of involvement

* Prior therapies

* Time from prior therapy.

.. But also patient characteristics:

* age,

* symptoms,

* short & long term goals

* co-morbidities (other medical conditions)

* preserve future options

==Future directions?

Dr. Czuczman favors trying to improve the induction protocols and use of

consolidation agents not used in the induction therapy. He favors clinical

trials of protocols with curative potential ... but until then, he favors

w & w - which he notes is still the widely accepted standard of care.

I don't recall if Leonard addressed future directions specifically, but I

expect he agrees with Czuczman on this, but that he is also interested in

testing approaches to manage the disease with less toxicity, by exploring

combinations of targeted drugs and immunotherapy, used as needed.

==Remaining questions after the debate?

* How do you measure the success of early use of Rituxan in asymptomatic

indolent lymphoma? And is observation a valid control (Adeshna)?

What is the optimal schedule if Rituxan is used first line? (The RESORT

study could well inform on this last question, but not my first question,

lacking observation or another type of treatment as a control.)

* Should " symptomatic " be scratched from published guidelines on need to

treat - based on its subjectivity, reliance on patient reporting, its

association with advanced and more aggressive disease status (if true)? Or

should it be maintained with a footnote: as an indication that the other

criteria for initiation of treatment may have been exceeded?

Karl

Patients Against Lymphoma

www.lymphomation.org

Bcc: advisors for comments and corrections.