[AlanB]

Dexamethasone during stem cell collection period?

by AlanB on Mon Dec 18, 2017 9:08 pm

My friend has been through 5 rounds of Kyprolis, Revlimid, and dexamethasone (KRD) and she is in a very good partial response. We want to collect stem cells after cycle 6, store them, and then continue more KRD while we consider whether or not to do transplant later on (if ever).

My concern is that, because treatment is stopped before collection, myeloma cells can proliferate during the collection period. I have seen a post on this forum of a relapse during the collection period.

I know we have to stop Revlimid before collection, because Revlimid does impair mobilization.

However, could dexamethasone be continued by itself during the collection period?

Dexamethasone has been used to suppress myeloma cell activity, so I think it would lower the risk of a relapse during the collection period. Also, at least one mobilization regimen actually used dexamethasone, along with the mobilization agents, as a preparation for collection (see reference below).

Would it make sense to use dexamethasone to suppress myeloma during the collection period? Does anyone know if this is sometimes done?

Any advice would be welcome.

Thanks,

Alan

Reference:

Green, DJ, et al, "Bendamustine, etoposide and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in patients with multiple myeloma," Bone Marrow Transplantation, May 2016 (full text of article)

Abstract

Chemotherapeutic agents without cross-resistance to prior therapies may enhance PBSC collection and improve patient outcomes by exacting a more potent direct antitumor effect before autologous stem cell transplant. Bendamustine has broad clinical activity in transplantable lymphoid malignancies, but concern remains over the potential adverse impact of this combined alkylator–nucleoside analog on stem cell mobilization. We performed a prospective, nonrandomized phase II study including 34 patients with multiple myeloma (multiple myeloma) (n=34; International Staging System (ISS) stages I (35%), II (29%) and III (24%); not scored (13%)) to evaluate bendamustine’s efficacy and safety as a stem cell mobilizing agent. Patients received bendamustine (120 mg/m2 IV days 1, 2), etoposide (200 mg/m2 IV days 1–3) and dexamethasone (40 mg PO days 1– 4) (bendamustine, etoposide and dexamethasone (BED)) followed by filgrastim (10 μg/kg/day SC; through collection). All patients (100%) successfully yielded stem cells (median of 21.60 × 106/kg of body weight; range 9.24–55.5 × 106/kg), and 88% required a single apheresis. Six nonhematologic serious adverse events were observed in 6 patients including: neutropenic fever (1, grade 3), bone pain (1, grade 3) and renal insufficiency (1, grade 1). In conclusion, BED safely and effectively mobilizes hematopoietic stem cells.

[TerryH]

Re: Dexamethasone during stem cell collection period?

by TerryH on Fri Dec 29, 2017 12:18 pm

Hi Alan,

If you are concerned about stopping therapy during the stem cell mobilization process, perhaps your friend should first try something like cyclophosphamide for mobilization, rather than the more common (in the U.S.) Neupogen.

Or perhaps her stem cell mobilization could be with the regimen described in the paper you cited (bendamustine, etoposide, and dexamethasone). Bendamustine (Treanda) is not widely approved by regulatory authorities as a myeloma therapy, but it has been tested extensively in myeloma patients. It's in the same class of nitrogen mustard alkylating agents as melphalan and cyclophosphamide. Etoposide also is a drug used to treat multiple myeloma, usually as part of the four-drug "PACE" regimen.

I did find this Chinese-language study that looked at Neupogen (aka G-CSF) plus dexamethasone versus just Neupogen for stem cell mobilization:

https://www.ncbi.nlm.nih.gov/pubmed/24156441

If my reading of the study abstract is correct, the group that got both Neupogen and dexamethasone mobilized fewer stem cells than the group that got just Neupogen. However, the reduced level of stem cell mobilization didn't seem to worry the researchers; they actually seemed to like the Neupogen+dexamethasone approach overall.

Note, as well, that the dexamethasone used in the Chinese study was 10 mg infused rather than given orally.

Good luck!

[AlanB]

Re: Dexamethasone during stem cell collection period?

by AlanB on Mon Jan 01, 2018 9:33 am

TerryH,

Thank you very much for responding. Unfortunately, as I understand it, the way medicine is practiced today, there is simply no way to suppress myeloma activity during the collection period.

So we're facing two options. Option 1 is to take the 4 to 6 weeks off treatment in order to collect stem cells for possible future use. The downside is that this lets up the fight against the myeloma, and gives the myeloma time to rebuild. Option 2 is to avoid collection and simply continue treatment without a break to attack the myeloma cells as potently as we can. The downside is that we forever “burn the bridge” of transplant. Medical issues aside, even the psychological effect of “burning the bridge” will be very real.