Impact of daratumumab on stem cell collection in patients with AL amyloidosis

Abstract Background Autologous stem cell transplantation following high-dose melphalan is an effective consolidation therapy for the initial treatment of systemic AL amyloidosis. While quadruplet induction therapy involving daratumumab is the standard-of-care, its impact on stem cell yield has not been studied. Furthermore, the relation of stem cell doses and long-term bone marrow function following quadruplet induction therapy remains unclear. It is unknown whether stem cell mobilization with G-CSF and plerixafor is comparable to that achieved with chemotherapy in AL amyloidosis. Methods We analyzed the impact of induction and mobilization regimens on stem cell yield in 180 patients using a prospectively maintained database. Descriptive analyses and multivariable logistic regression analyses were performed for collection outcomes. The primary endpoint was overall stem cell collection yield. Results The median age at diagnosis was 55 years, with 62% of patients being male. Organ involvement included heart in 48% and kidney in 60% of patients. For induction, 51% of patients received a bortezomib-based regimen (e.g. CyBorD or BorD), 15% received a daratumumab-containing regimen and 27% underwent chemotherapy-free induction therapy. Chemo-free mobilization with G-CSF was performed in 23% of patients, while 39% received cyclophosphamide and dexamethasone (CD) and 33% received cyclophosphamide, adriamycin and dexamethasone (CAD). The total collection after chemo-free mobilization was lower compared to CD and CAD (5.44 × 10⁶ versus 7.29 × 10⁶ versus 9.69 × 10⁶ CD34/kg, p < 0.001). Daratumumab decreased the yield compared to chemotherapy-free induction (5.93 versus 9.24 × 10⁶/kg, p = 0.013) and showed a negative trend compared to bortezomib-based regimen (8.01 × 10⁶/kg, p = 0.147) in univariable analysis. Multivariable logistic regression analysis showed that daratumumab-exposed patients collected stem cell products of > 6.5 × 10⁶/kg less often (Odds ratio (OR) 0.40, p = 0.079). The same was true for patients undergoing mobilization with G-CSF and without plerixafor (OR 0.32, p = 0.012). Stem cell transplantation with > 6.5 × 10⁶/kg might improve short-term and long-term bone marrow function, as reflected by a lower incidence of thrombocytopenia. Conclusion Mobilization regimens had a stronger impact on stem cell yield than induction therapies. Stem collection is feasible after DaraCyBorD, however, high stem cell doses should be applied to maintain adequate bone marrow function.