AL Amyloidosis: A Good Response That Doesn't Settle Whether Transplant Is Still Worth the Risk
A very good partial response to induction is the standard signal to proceed to transplant in myeloma, and much of the instinct to transplant this patient is borrowed from that setting. Her disease has infiltrated the organ that conditioning stresses most.
R.K., a 63-year-old former dental hygienist, was diagnosed with AL amyloidosis after unexplained fatigue and lower-extremity swelling led to an evaluation that found an elevated free light chain ratio and a fat pad biopsy positive for amyloid. Her cardiac biomarkers put her at Mayo stage II — a modestly elevated troponin, a moderately elevated NT-proBNP — and the staging system exists because those two numbers, rather than any symptom she reports, are what predict how this disease kills people. Stage II is the middle: enough infiltration to be staged by it, not enough to have declared itself. Her proteinuria is present with a preserved eGFR, which is the same story told by the kidney. She completed four cycles of daratumumab, cyclophosphamide, bortezomib, and dexamethasone, tolerating induction well, and repeat testing showed a very good partial response: a substantial reduction in her involved free light chain and improving energy, though not yet a complete hematologic response.
In myeloma, a very good partial response in a transplant-eligible patient reads as straightforward grounds to consolidate, and much of the instinct to transplant her is borrowed from that setting. The borrowing is where the difficulty lies, though not quite in the way the older literature suggests. Transplant-related mortality in AL amyloidosis was once dramatically higher than in myeloma — the Boston University series of 421 patients reported 11.4% across fifteen years, and early single-center experience ran far above that — but Sidiqi and Gertz's Mayo cohorts show it falling from 14.5% to 8.6% to 2.4% across successive eras, which is myeloma territory. What produced that fall was not a gentler conditioning regimen. It was selection, and the thing selected on was cardiac biomarkers: Mayo's own eligibility criteria set a troponin T ceiling below which patients are offered transplant and above which they generally are not. R.K.'s troponin is modestly elevated, which is precisely the region those criteria were written to adjudicate — so the reassuring modern mortality figures describe a population she may or may not belong to, and nobody in the room has yet checked which. Her four well-tolerated cycles and falling light chain are real evidence about her plasma cells' sensitivity to chemotherapy, which is not the organ the question is about.
Amyloidosis multidisciplinary conference
Her very good partial response to induction demonstrates real chemosensitivity, and in an eligible, responding patient, consolidative autologous transplant has a long history of deepening and extending remission in AL amyloidosis specifically. She tolerated induction well — that's itself meaningful evidence about her capacity to tolerate more intensive therapy.
I'd separate those two kinds of tolerance, and I'd also update the number you're implicitly using. Transplant-related mortality in amyloidosis is no longer what it was — Sidiqi's Mayo series has it down to 2.4% in the most recent era, against 14.5% in the earliest. But that improvement came from selection rather than technique, and the selection variable was cardiac biomarkers. Her troponin is elevated, modestly, which puts her near the line those eligibility criteria draw rather than comfortably inside it.
So citing modern mortality figures at me isn't quite the argument it sounds like. Those figures were generated by excluding patients whose troponin looked like hers, and tolerating four cycles of induction is not the test that decides which side of that line she sits on.
Chemosensitivity and conditioning tolerance are genuinely different physiologic questions, and only one of them has actually been tested in her so far.
I'd raise a further question underneath both of yours: ANDROMEDA's own data showed daratumumab-based therapy producing deep, sustained responses without transplant at all. Given how well she's already responding to daratumumab-CyBorD, is there even a demonstrated incremental benefit to adding transplant on top of that response in the current treatment era — or is continued daratumumab-based maintenance alone a genuinely sufficient endpoint now, without needing transplant's added risk to reach it?
Not agreed, and left genuinely unresolved: whether transplant's traditional role in AL amyloidosis still holds an incremental benefit over modern daratumumab-based therapy alone — the hematologist-oncologist's reframing of the question was accepted as the more current way to state it, without the group actually answering it.
What was agreed for now: continue daratumumab-based maintenance and reassess in six months, rather than proceeding to transplant on the strength of her induction response alone, given the cardio-oncologist's real, disease-specific mortality concern even at her currently mild cardiac stage.