molecularly tailored maintenance therapy?

[Guest guest]

Greetings,

One aspect of maintenance Rituxan that I'm uncomfortable with is the risk of

receiving more therapy than is needed ... such as when you may already be in

a " deep " remission from R-CHOP. (Not firing until you have something to

shoot.)

This report provides the rationale for investigating if the schedule of

maintenance Rituxan (or continued observation) could be based on very

sensitive PCR testing instead of a one-size-fits-all approach.

The test, PCR, having an analytical sensitivity of 1 tumor cell in 100,000

normal cells. - a level of disease that is otherwise not detectable. The

sample would be from the blood or marrow - the compartment tested not

specified in the abstract below.

The result of the PCR test might also be the basis for deciding if more

aggressive or consolidation therapy should be considered, depending on the

indication. Presumably it can give you a " heads up " about relapse well

before you would otherwise detect it with imaging or by clinical symptoms.

The low level of disease perhaps making the intervention you choose at that

time more effective compared to treating advanced disease.

But there are issues with molecular testing with PCR.

.... While very sensitive at detecting tumor cells it cannot inform about the

status of the lymphoma in lymph nodes. However, I wonder if agents that may

be able to induce lymphoma cells in nodal areas to mobilize -- to disengage

from bystander cells in lymph organs and circulate in the blood? (As is done

to mobilize stem cells for harvesting.) This might allow PCR evaluations of

blood sample to detect cells in this compartment as well.

Karl

==

Biol Blood Marrow Transplant. 2006 Dec;12(12):1270-6.

Rituximab induces effective clearance of minimal residual disease in

molecular relapses of mantle cell lymphoma.

http://www.ncbi.nlm.nih.gov/pubmed/17162208

Abstract

Molecular remission (MR) is associated with improved outcome in mantle cell

lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse.

We retrospectively describe the molecular and clinical follow-ups of 4

patients with molecular relapses (M-rels) who were treated with rituximab.

The 4 patients received rituximab-supplemented, high-dose sequential

chemotherapy and autologous stem cell transplantation as induction treatment

and achieved clinical remission and MR. M-rel was defined as polymerase

chain reaction (PCR) positivity in 2 consecutive samples in the absence of

clinical relapse.

M-rels occurred at 3, 6, 39, and 52 months and were always confirmed by

direct sequencing of the clonal rearrangement.

Minimal residual disease was monitored by qualitative and real-time

quantitative PCR.

All patients received 4 courses of rituximab, with 2 additional infusions if

PCR positivity remained. After 4-6 courses of rituximab, all patients

re-entered MR. No clinical relapses were recorded at 3, 6, 18, and 62 months

from treatment, although 1 patient had a second M-rel that was sensitive to

rituximab. Our results indicate that rituximab is active against residual

MCL cells and suggest that molecularly tailored maintenance therapy needs to

be investigated in clinical trials.

PMID: 17162208

Ladetto M, Magni M, Pagliano G, De Marco F, Drandi D, Ricca I, Astolfi M,

Matteucci P, Guidetti A, Mantoan B, Bodoni CL, Zanni M, Boccadoro M, Gianni

AM, Tarella C.

Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale,

Università di Torino, Torino, Italy. marco.ladetto@...