A Score Model for Predicting Unsuccessful or Sub-Optimal Peripheral Blood Stem Cell Collections in Multiple Myeloma Based on a Retrospective Analysis of 1,039 Patients Receiving Novel Agents As Induction Therapy and Cyclophosphamide Plus G-CSF As Mobilizing Regimen,

Abstract 4044

Induction therapy with the so-called “novel agents” (bortezomib or IMIDs) followed by autologous stem cell transplantation (AuSCT) is considered the current standard therapeutic approach for younger patients with multiple myeloma (MM). However, a variable proportion of these patients still fails to mobilize and to collect a number of CD34+ peripheral blood stem cells (PBSC) sufficient for a safe transplant procedure or, as required in selected patients, for double or salvage AuSCTs. The aim of this study was to analyze, in a large number of MM initially treated with novel agents and homogeneously mobilized, the role of some potential risk factors on PBSC collection in patients eligible for AuSCT.

To this purpose, the impact of age > 60 years, baseline cytopenia at diagnosis (Hb< 10 g/dl and/or neutrophil count < 1,000/μl and/or platelet count < 100,000/μl), initial use of lenalidomide and grade 3–4 hematological toxicity during induction therapy were retrospectively evaluated in 1,337 previously untreated MM patients enrolled in five consecutive clinical trials finalized to AuSCT and conducted by GIMEMA cooperative Group and MM Italian Network. In all cases, the mobilizing regimen was cyclophosphamide + G-CSF. In four of these studies, including 1,039 patients, induction regimens had comprised novel agents: thalidomide (TD, 296 patients), bortezomib (PAD, 121 patients), thalidomide plus bortezomib (VTD, 219 patients), lenalidomide (RD, 403 patients). 298 patients treated with a VAD-modified induction regimen (DAV) were also evaluated. Data were retrospectively extracted from two different databases of the coordinating Centers (Torino and Bologna) using a single, dedicated excel file. Total amounts of less than 2 and less than 5 × 10e6/kg CD34+ PBSC after a single mobilizing procedure were considered as “unsuccessful ” or “sub-optimal” results, respectively.

Overall, 917 patients (68.6%) showed the presence of at least one risk factor: 615 patients (46%) had only 1 parameter, 302 a combination of 2 (n. 237, 17.7%), 3 (n. 56, 4.2%) or 4 (n. 9, 0.7%) parameters, respectively. After a single PBSC mobilization, 413 patients (30.9%) had a sub-optimal result, including 256 patients (19.1%) with unsuccessful collection. Any single parameter negatively influenced PBSC collection vs absence of parameters (p < 0.000). At multivariate analysis, however, grade 3–4 hematological toxicity (p < 0.000) and the use of lenalidomide (p < 0.013) during induction showed the most powerful negative effects on mobilization. The number of present risk factors (from 4 to 0) significantly paralleled the ineffective procedures, both in terms of absolute median amount of CD34+ PBSC collected (from 1.2 to 10.6 × 10e6/kg) or percentage of unsuccessful/sub-optimal collections (from 78% to 13% and from 89% to 24%, respectively) (p < 0.000). On these basis, we constructed a predictive score where the four parameters were pooled and weighted according to their relevance as single or combined variables, attributing the value of 3 for grade 3–4 hematological toxicity, 2 for the use of lenalidomide and 1 each for age > 60 and baseline cytopenia. Applying this model, we found that the risk of collecting less than 2 (27.5% vs 17.3%) and less than 5 (41% vs 28.6%) × 10e6/kg CD34+ PBSC, was significantly higher in patients with a total score equal or >3 than in patients scored <3 (p < 0.000 for both comparisons). These data did not differ significantly when the patients who had not received novel agents as induction therapy were excluded from the analysis.

In conclusion, our score model provides a simple and effective method to predict unsatisfactory PBSC collections in MM patients eligible for AuSCT who have received novel agents as induction therapy and a combination of chemotherapy plus G-CSF as mobilizing treatment.