A multicenter study published in Cancers offers retrospective data on the efficacy of BCL-2-inhibitor venetoclax for relapsed or refractory (R/R) light-chain (AL) amyloidosis.1 In a study of 26 patients across seven centers in Israel, Greece, and Italy, 35% of patients achieved a complete response (CR), with an overall response rate of 88%, researchers reported.
Iuliana Vaxman, MD, principal investigator and oncologist at the Davidoff Cancer Center in Israel, said the findings were very encouraging. “[Hematologic] responses were deep, and this is the most important endpoint in amyloidosis,” she said.
Prior studies have shown venetoclax to work well in the disease, but data are still limited, researchers noted.
In this study, researchers identified all patients with AL amyloidosis who had received at least one dose of venetoclax outside of a clinical trial. The patients’ median age at the time venetoclax was started was 65 (range = 50-88), with 10 patients who were at least 70. Eight patients had concurrent multiple myeloma (MM).
Eighty-eight percent of the patients had the chromosomal translocation t(11;14), which indicates susceptibility to BCL-2 inhibition. This amount is considerably higher than the 50% seen in the general population of patients with AL amyloidosis.2 Sixteen percent had high-risk cytogenetics.
Patients had been treated with a median of 3.5 prior lines of therapy. Most patients had cardiac and renal involvement (77% and 58%, respectively).
Nine patients (35%) received venetoclax monotherapy and nine others received it in combination with dexamethasone. Eight people received it with daratumumab (with or without dexamethasone), and one person received venetoclax in combination with daratumumab, bortezomib, and dexamethasone.
In addition to the CRs, 35% of the patients achieved a very good partial response, 19% a partial response, and 12% no response. The median duration of response was 25 months.
Evaluation of organ responses using biomarkers was not possible for many patients due to missing data, but five documented cardiac responses were seen, and two patients were deemed to have “marked clinical improvement” of heart failure. Four renal responses and two hepatic responses were also reported, researchers reported.
Three of the patients did not harbor the t(11;14) chromosomal translocation. Of these, one patient achieved CR, one patient achieved a partial response, and one patient had no response.
At a median follow-up of 33 months, 20 patients (77%) were still alive. The median event-free survival was 25 months, and median overall survival was 33 months. Five patients died from disease complications and one due to infection.
There were nine grade 3 to 5 toxicities among five patients, including three infections and one case of diarrhea; the others were hematologic toxicities. Ten patients had their doses reduced, but the duration of response was similar for those with and without dose reductions, researchers reported.
“At data cut-off, most of the patients in this cohort are in ongoing deep responses and continuing therapy with venetoclax,” the researchers noted. “The efficacy of venetoclax reported here is especially encouraging, since this is a heavily pretreated cohort.”
Patients with AL amyloidosis are often frailer than patients with MM, mostly due to their cardiac involvement and presentation with heart failure, and medications that are tolerable for these patients are needed.
“Since this diagnosis is often missed, [patients] often present in advanced stages with low performance status and malnourishment,” she said. “It is such an important medication for this indication.”
Any conflicts of interest declared by the authors can be found in the original article.
References
- Lebel E, Kastritis E, Palladini G, et al. Venetoclax in relapse/refractory AL amyloidosis-a multicenter international retrospective real-world. Cancers (Basel). 2023;15(6):1710.
- Bryce, AH, Ketterling, RP, Gertz, MA, et al. Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis. Haematologica. 2009;94(3):380-386.