In transplant-eligible, fit patients with primary refractory myeloma, what is the optimal timing for stem cell collection?

In fit patients with less than a partial response to induction therapy, i.e. primary refractory, the optimal timing for stem cell collection is NEVER. If they don't respond to three drug induction (proteasome inhibitor + IMiD + steroid), they are unlikely to respond durably to a standard high dose melphalan transplant.

There is not great literature on this -- these patients are approximately 2-3% of the newly diagnosed clinical trial population per IFM-2009 (Attal et al, NEJM, 2017) or 6-8% of those that have been induced in the community and then go on to a transplant trial (BMT CTN 0702, Stadtmauer, JCO, 2019).

The older PETHEMA data on how these patients do with autologous transplant of primary refractory myeloma is too rosy as the patien...

I will take a different tactic in these primary refractory disease cases.

I typically employ a VD-PACE like regimen and give for 2 cycles. Then use the second cycle as part of chemomobilization for stem cell collection, followed by high dose melphalan and stem cell rescue. After transplant, I then will use triplet therapy with drugs not yet utilized (i.e. Dara/Kd being my preference if used VRd upfront). The duration of remission probably won't be as durable as others, but meaningful enough that it works and can be utilized.

CAR T-therapy is not an option off protocol for primary refractory disease at this time, but this could be a viable option in the future.

Adding an updated response as requested by theMednet editorial team :) I agree with everything in @Dr. First Last's response from 3 years ago. For patients with primary refractory myeloma, even collecting stem cells is probably low-yield especially since it's not benign. And while continued len exposure might make collection harder down the line, trying to mobilize stem cells in someone with a high bone marrow PC burden might be just as hard.

The big update since this original answer in 2019, of course, is the advent of standard-of-care CAR T and other advanced immune-based therapies: belantamab now, teclistamab soon, etc. While most of these wouldn't yet be commercially available as second-line therapies, this is under investigation: e.g.,...