Neutropenia and Imbruvica

[MikeOr]

What happens when you are getting neutropenic while taking Imbruvica ? Is your dose is reduced, or Imbruvica is stopped until numbers improve, or something else ?

[AussieNeil Administrator]

From imbruvica.com/docs/librarie...

2.2 Dosage Modifications for Adverse Reactions

Interrupt IMBRUVICA therapy for any Grade 3 or greater non-hematological toxicities, Grade 3

or greater neutropenia with infection or fever, or Grade 4 hematological toxicities. Once the

adverse reaction has improved to Grade 1 or baseline (recovery), IMBRUVICA may be reinitiated at the starting dose. If the adverse reaction reoccurs, reduce dose by 140 mg per day.

Consider a second reduction of dose by 140 mg as needed. If these adverse reactions persist or

recur following two dose reductions, discontinue IMBRUVICA.

[lankisterguy Volunteer]

When it happened to me I was given a Neulasta injection, Neupogen is an alternative verywellhealth.com/neulasta....

Len

[MikeOr in reply to lankisterguy]

I was told that injecting Neupogen or Neulasta would activate bone marrow while Imbruvica is calming it down, so these medications have opposite effects and, so, should not be used together.

[AussieNeil Administrator in reply to MikeOr]

Mike, I seem to recall you mentioning this before. It would be good if you can find some reference for this approach, which could explain why G-CSF is not included in the recommended management response I referenced above.

G-CSF drugs like Neupogen, Neulasta, Filgrastim, Zarzio and so on stimulate neutrophil production in the bone marrow. CLL treatment drugs tend to suppress neutrophil production in the bone marrow, with Venetoclax in particular having a reputation in this regard. Yet G-CSF and or dose reduction is a recommended treatment for neutropenia while taking Venetoclax, particularly if trying to maintain adherence to an infusion cycle with Rituximab or Obinutuzumab. I was prescribed G-CSF shots as needed - and early on that was several times a week, while on an Acalabrutinib (a second generation version of Ibrutinib), Venetoclax and Obinutuzumab trial.

Neil

[lankisterguy Volunteer in reply to MikeOr]

Neulasta & Neupogen are stimulants in the bone marrow production of Neutrophils - en.wikipedia.org/wiki/Neutr...

rxlist.com/neulasta-drug.ht...

which are very different than B-cells / lyphocytes. en.wikipedia.org/wiki/B_cel....

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Your characterization of the mechanism of Ibrutinib / Imbruvica is not consistent with what Pharmacyclics says. I would paraphrase it to say that Ibrutinib changes the way that B-cells behave, preventing them from adhereing and homing to the lymph nodes. The action is not described as having primary impact in the bone marrow. please see this: -

pharmacyclics.com/home/our-....

and this

personalizedmedonc.com/arti...

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SNIP: Ibrutinib is a small molecule that works by inhibiting a type of enzyme, called a protein kinase, that controls the rate at which certain cells multiply. In particular, ibrutinib has been shown to covalently bind to, and ultimately inhibit, the Bruton’s tyrosine kinase (BTK) While BTK plays a primary role in signaling healthy B cells to mature, release antibodies and proliferate, B-cell cancers (which include chronic lymphocytic leukemia and most non-Hodgkin’s lymphomas) also depend on BTK in the same way to survive.

Nonclinical studies have shown that BTK inhibition prevents tumor cell adhesion, migration and homing (returning to lymph organs to proliferate), along with increase in cancer cell apoptosis (programmed cell death) and inhibition of proliferation.

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Len