P-353: Stem-Cell Mobilization and Transplantation in Newly Diagnosed Multiple Myeloma Patients Treated With Carfilzomib-Lenalidomide-Dexamethasone With or Without Isatuximab: Results From the IsKia Trial

Introduction: In the phase 3, randomized EMN24/IsKia trial, the addition of isatuximab to carfilzomib-lenalidomide-dexamethasone (Isa-KRd) as induction and consolidation in transplant-eligible NDMM patients (pts) significantly improved the measurable residual disease negativity (10^-5) rate at the end of consolidation (Isa-KRd 77% vs KRd 67%, p=0.049). Here we present a preplanned analysis on stem-cell (SC) mobilization and collection and transplantation outcomes.

Methods: Pts received 4 28-day induction cycles with Isa-KRd vs KRd and subsequently started SC mobilization 4–6 weeks after day 21 of cycle 4 with either cyclophosphamide (Cy; 2–3 g/m²) plus granulocyte colony-stimulating factor (G-CSF; 10 µg/kg) from day 5 until SC collection was completed or G-CSF alone ±plerixafor (PLX) according to its label. Pts received autologous SC transplantation (ASCT) conditioned with melphalan at 200 mg/m².

Results: 302 pts were randomized to Isa-KRd (151) or KRd (151) induction. 140 (93%) vs 141 (93%) pts in the Isa-KRd vs KRd arms started SC mobilization at a median time of 25 days from the end of induction. A similar percentage of pts in the Isa-KRd (97%) vs KRd (99%) arms completed SC mobilization (p=0.4). A higher percentage of pts in the Isa-KRd (75%) vs KRd (62%) arms received Cy as part of mobilization (p=0.02); PLX use was similar in the two arms (39% vs 29%, p=0.1). The median number of CD34⁺ SCs collected was 5.0×10⁶ cells/kg (IQR 3.7×10⁶–6.6×10⁶) in the Isa-KRd vs 5.5×10⁶ (IQR 3.8×10⁶–7.8×10⁶) in the KRd arm (p=0.14). The median number of apheresis days was 2 (IQR 1–2) in the Isa-KRd vs 1 (IQR 1–2) in the KRd arm (p=0.08). The successful mobilization rate (≥2×10⁶ cells/kg) was similar in pts mobilized with Cy+G-CSF vs G-CSF (99% vs 96%, p=0.2), although a higher SC yield was obtained with Cy+G-CSF vs G-CSF (6.37×10⁶ vs 3.74×10⁶ cells/kg; p< 0.001), without significant differences in the two induction arms.

A second mobilization, mostly with G-CSF±PLX (73% of pts) was performed in 19 pts (14%) in the Isa-KRd and 7 pts (5%) in the KRd arm, mainly due to <2.0×10⁶ cells/kg collected with the first attempt (15 vs 6 pts); of these, 15 vs 7 pts in the Isa-KRd vs KRd arms successfully completed SC collection.

Among pts who underwent mobilization, 134 (95%) in the Isa-KRd vs 137 (97%) in the KRd arm underwent ASCT. The median number of CD34⁺ transplanted cells was 3.1×10⁶ cells/kg (IQR 2.4×10⁶–4.0×10⁶) in the Isa-KRd vs 3.3×10⁶ (IQR 2.7×10⁶–4.4×10⁶) in the KRd arm (p=0.10).

The median time to neutrophil recovery (≥0.5×10⁹/L) was 15 days (IQR 12–27) in the Isa-KRd vs 14 (IQR 12–27) in the KRd arm (p=0.3); the median time to platelet recovery (≥20×10⁹/L) was 18 days (IQR 14–24) in the Isa-KRd vs 16 (IQR 13–24) in the KRd arm (p=0.1).

Conclusions: SC collection with either Cy+G-CSF or G-CSF was feasible after KRd ±isatuximab induction in the majority of pts and allowed for hematopoietic reconstitution in all transplanted pts. The upfront use of PLX could be considered to optimize SC collection.