P25 effect of daratumumab on stem cell yields in patients with newly diagnosed multiple myeloma: report from the multiple myeloma lazio group

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care therapy for newly diagnosed multiple myeloma (NDMM) patients (pts). The anti-CD38 IgG1-k monoclonal antibody daratumumab (dara) demonstrated to improve depth and duration of response in transplant eligible MM pts when added to the standard of care induction regimen. Recent studies have indicated a potential reduction in stem cell yields in MM pts exposed to dara prior to stem cell mobilization. We retrospectively evaluated 51 pts with NDMM managed at 8 Italian Hematology Centers who underwent induction therapy based on dara-bortezomib, thalidomide and dexamethasone (D-VTD) between November 2021 and July 2022. Following induction, pts underwent mobilization therapy as per institutional guidelines. The primary endpoint of this study is to investigate the possible impact of dara on stem cell yields with mobilization therapy and to identify possible features that affect stem cell yields. Fifty-one pts were included in the analysis. The median age was 60 (range: 54-64); 65% were male; 49% of pts were stage I, and 37% were stage II, according to the International Staging System (ISS) and the Revised- ISS, respectively. Forty-eight pts (94%) received 4 cycles of D-VTD as induction therapy after mobilization therapy. The baseline clinical characteristics and the frontline induction therapy were summarized in Table 1. Globally, 48 out of 51 pts (94%) analyzed, met the collection goal after mobilization therapy, however, for 3 pts (6%) a second mobilization attempt was required. In addition, for another 3 pts (6%) a third mobilization attempt was needed. In the majority of pts (92%), a combination of cyclophosphamide with granulocyte colony stimulating factor was used as the first mobilizing regimen attempt. Plerixafor on demand was administered during stem cell mobilization in 15/51 pts (32%) failing to achieve the desired collection goals, confirming that a higher use of plerixafor was necessary in the dara-based induction therapy, as previously reported1. Specifically, 14 out of 15 pts (99%) met the collection goal at the first mobilization therapy attempt receiving plerixafor on demand, and most of these pts (71%) received only one dose of plerixafor. The majority of the pts who did not meet the goal in one apheresis procedure were able to meet the goal with 1 (64%) or 2 (10%) additional procedures. The median number of CD34+ stem cells collection yield was 8 x 106 cells/Kg (range: 1.4-16). The median time between the last day of induction therapy and the first day of mobilization therapy was 31 days (range: 25-45). Univariate analysis showed that a higher level of baseline LDH was associated with a lower rate of collection goal, after the first mobilization attempt (p=0.017). Pts with a median lower pre-mobilization therapy level of neutrophils and platelets showed a significantly lower rate of collection goal after the first mobilization attempt (p=0.013 and p=0.035, respectively), possibly due to prolonged hematological toxicity after induction therapy. On introducing dara to the induction treatment, we observed that a higher use of plerixafor and more days of apheresis procedures are required to meet the collection goal at the first mobilization attempt. A larger cohort of pts are needed to confirm our results and to evaluate a new mobilization therapy schedule to guarantee adequate stem cell yields. 1] Hulin C et al. Haematologica 2021 Table 1 - Baseline patient’s clinical characteristics and the frontline induction therapy Characteristics Patients (N= 51) % Gender Male Female 3318 6535 Age (years) Median (range) 60 (54-64) Type of Heavy chain G A Absent 31118 622216 Type of Light chain type κ λ 3516 7129 ISS I II III 251511 492922 Cytogenetic abnormalities, n (%) High risk Standard risk Not evaluable/missing 23208 433916 CRAB Hypercalcemia Renal insufficiency Anemia Osteolytic bone lesions 1051945 20103888 R-ISS I II III NA 1719105 37412213 Response after induction therapy sCR CR VGPR PR 79287 14185514 Cycle of induction therapy, n (%) 4 2 483 946 Bone marrow plasma cell infiltration Median (range) 60 (38-74) Bone marrow function pre-mobilization therapy, median (range) Hb, g/dl Platelets, mm3 Neutrophils, mm3 13.2 (12.25-13.90)222 (170-298)2580 (1865-3905) Induction therapy toxicity Haematological Anemia Thrombocytopenia Leucopenia Non-Haematological Neuropahty Infections Gastroenteric Skin rash Cardiac 124 141732 248 2721464