Re: CAL-101 and bone marrow clearance

[Guest guest]

Larry,

You wrote (in part):

" Unless there is massive reduction in bone marrow infiltration these patients

will relapse all too soon. "

I believe we need to think about CAL-101 response differently than we do the

currently approved treatments. The existing treatments are given over a fixed

time period (generally 6 months as they are too toxic to be taken long term). At

that point, we hope to have reached a remission and that we won't relapse too

soon.

CAL-101 is taken continually over a long term, possibly the rest of your life

(as insulin is taken by diabetics). At this point, there are no known harmful

effects of taking CAL-101 for the majority of patients. Of course, some harmful

effects may eventually become apparent as the trials continue.

Another question is, " Will CAL-101 continue to be effective over the long term? "

Is it possible the CLL cells will find a way to thrive in spite of CAL-101? Or

will the body start to filter out the CAL-101 before it can do its work?

I've been thinking a lot about these last questions myself. CAL-101 has worked

wonderfully for me, but my lymphocyte count has now started to go up again. My

ALC was 106 when I started the trial. It went up to 157 at the end of cycle 1.

It then started dropping steadily reaching a low of 9.5 at the end of cycle 8.

It was 13.6 after cycle 10 and 19.5 after cycle 12. My HGB and platelet counts

have continued to improve (to 11.9 and 74 after cycle 12). I am now on the

extension trial at the same dosage (300mg once per day) and hoping for the best.

Happy New Year,

Don Keller

[Guest guest]

It has been stated that in the CAL 101 clinical trials bone marrow biopsies were

performed pre-treatment but not afterwards. Assuming this is true, then this is

not a standard CLL drug trial protocol and seems incomplete. As to CBC

reflecting bone marrow clearance, I have experienced multiple instances of

relatively good CBC results but high bone marrow involvement. In the end it is

the bone marrow which is the heart, so to speak, of this disease and not to have

post treatment BMBs seems very strange.

[Guest guest]

Not at all. The response classes for CLL are going to be either progressive

disease (PD), stable disease (SD), partial response (PR), complete response

(CR), and complete response with incomplete marrow recovery (CRi). The current

criteria no longer use nodular PR (nPR).

End of study bone marrows would typically only be done if they were to change

the response category. If a patient has had a " great " response, with resolution

of all nodes, normalization of WBC, hemoglobin and platelets, but still with a

lymphocyte count of 6,000, then the patient is a PR. Eventhough this might be a

truly amazing response. Because of the lymphocytes present in the blood, no

matter what the bone marrow shows, it will be a PR. Likewise, if the CBC is

completely normal, doing the bone marrow will further determine whether the

response is a CR.

Regarding the question of having a normal CBC, but a lot of CLL in the marrow,

most of the bone marrow is empty space, taken up by fat, so you there can stil

be a great deal of CLL present, even with normal counts. The percentage of bone

marrow involved on a biopsy is very misleading, as it can vary from site to

site. The CBC holds the advantage of being a better assessment of the marrow in

its entirity.

Rick Furman

>

>

>

>

> It has been stated that in the CAL 101 clinical trials bone marrow biopsies

were performed pre-treatment but not afterwards. Assuming this is true, then

this is not a standard CLL drug trial protocol and seems incomplete. As to CBC

reflecting bone marrow clearance, I have experienced multiple instances of

relatively good CBC results but high bone marrow involvement. In the end it is

the bone marrow which is the heart, so to speak, of this disease and not to have

post treatment BMBs seems very strange.

>

[Guest guest]

No minimal residual disease (MRD)?

~chris

> Not at all. The response classes for CLL are going to be either progressive

disease (PD), stable disease (SD), partial response (PR), complete response

(CR), and complete response with incomplete marrow recovery (CRi). The current

criteria no longer use nodular PR (nPR).

[Guest guest]

The current response criteria only use routine testing and not MRD assessments.

>

> No minimal residual disease (MRD)?

>

>

> ~chris

>

>

> > Not at all. The response classes for CLL are going to be either progressive

disease (PD), stable disease (SD), partial response (PR), complete response

(CR), and complete response with incomplete marrow recovery (CRi). The current

criteria no longer use nodular PR (nPR).

>

[Guest guest]

Which CBC parameters do you look at to evaluate bone marrow infiltration?

---------------------------

> The CBC parameters are the best means for evaluating marrow infiltration. A

bone marrow biopsy will only look at one site, but the CBC measures what is

important, the function of the remaining marrow.

> Rick Furman, MD