Researchers Assess Utility of Response Criteria for AL Amyloidosis Therapy

A study from researchers at the University of Pavia in Italy, confirmed that current response criteria for an amyloid complete response (aCR) based on free light-chain (FLC) measurement should remain the therapy goal for light-chain (AL) amyloidosis.

In AL amyloidosis treatment, aCR is defined as negative serum and urine immunofixation (IF) with normalized FLC ratio (FLCR). Low levels of involved FLC (iFLC) or difference between iFLC and uninvolved FLC (dFLC) have also been reported to be associated with prolonged overall survival (OS) and may be effective treatment goals.

The investigators conducted this study to validate whether low FLC levels are sufficient predictors of superior survival to update currently validated hematologic response criteria for AL amyloidosis. They enrolled 434 consecutive patients who were treated for AL amyloidosis at the Amyloidosis Research and Treatment Center of Pavia. Patients received a first-line treatment that was bortezomib-based (60%), oral melphalan plus dexamethasone (29%), immunomodulatory-based (5%), autologous hematopoietic cell transplant (3%), or therapy for immunoglobulin M clones (2%).

Participants were divided into five groups based on response after six months post-treatment initiation: aCR (n=161); iFLC <20 mg/L (n=66); normalized-iFLC (n=114); dFLC <10 mg/L (n=144); and normalized FLC ratio (n=220). The median follow-up was 55 months and median OS was 93 months.

Similar OS was found in patients who achieved aCR and those with iFLC <20 mg/L (median OS not reached) but was inferior in all other groups (median OS, 79-91 months). Median time to next therapy or death was longer in the aCR group (69 months) compared with any FLC endpoint group (18-39 months).

The investigators also assessed efficacy of alternative definitions of CR, based on negative serum and urine IF and substituting normal FLCR with each of the low-FLC endpoints, to discriminate patients who survived longer than two years. None of the alternative definitions showed better performance than aCR.

“In conclusion, available data do not support an update of response criteria based on FLC measurement, and aCR should remain the goal of therapy if tolerability allows. Negative serum and urine immunofixation should remain part of the definition of CR,” the authors wrote.

This study was published in Blood Cancer Journal.