Abstract Topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Background: Quadruplet induction with Daratumumab, Bortezomib, Thalidomide and Dexamethasone (Dara-VTd) has become the standard treatment for transplant-eligible newly diagnosed multiple myeloma patients (NDMM). Despite improved response rates compared to VTd, concerns with stem-cell mobilization and collection emerged in CASSIOPEIA trial. Indeed, after a mobilization approach based on cyclophosphamide (2 to 3 g/m2) and granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/day, patients treated with Dara-VTd experienced a greater use of plerixafor as well as a lower median number of collected CD34+ cells/Kg.
Aims: Here we report our retrospective, multicenter experience on stem cell mobilization with cyclophosphamide 4 g/m2 and G-CSF after Dara-VTD induction.
Methods: We retrospectively analyzed our real-life data on stem cell collection in 43 consecutive transplant-eligible NDMM patients treated with Dara-VTd in two Italian hospitals (IRCCS Ospedale San Raffaele, Milano; Ospedale Civile Santo Spirito, Pescara). Mobilization was performed with high-dose cyclophosphamide 4 g/m2 (HD-CTX) and G-CSF, either in an inpatient or outpatient setting according to center preference. Plerixafor 0,24 mg/kg was administered on demand as per institutional practice.The pre-planned collection target was 10 x 106 CD34+/kg.
Results: Between December 1st, 2021 and February 28th, 2023, 43 NDMM completed Dara-VTd induction at our institutions, with a 98% overall response rate. After a median of 132 days (IQR 124 to 151 days) from start of induction, 42 patients received HD-CTX, of which 17 (39%) in an outpatient setting. Of these 17 patients treated in an outpatient setting, 3 (18%) had G3 febrile neutropenia requiring hospitalization, that promptly resolved after antibiotic treatment and leukocyte recovery. No other grade 3-4 adverse events were reported. Successful mobilization was reached in 39/42 patients (93%). Median number of cells collected was 10 × 106 CD34+/kg (IQR 9,01 × 106 to 11,48 × 106), with the lowest collection procedure yielding a total of 4,92 × 106 CD34+/kg. Total G-CSF administered per patient was 5,73 MU/kg +/- 2,07 (mean +/- SD). Median time from CTX to first day of apheresis was 11 days (IQR 10 to 13), with 27 patients (64,2%) needing 2 days of apheresis to complete cell collection (range 1-2). Plerixafor was needed in 18 patients (46%). 1 patient discontinued mobilization due to concomitant Sars-Cov2 infection and subsequent rescue attempts (chemo-free and CTX 2 g/m2 based) failed. 2 patients failed to mobilize adequate numbers of CD34+ and did not start the collection procedure: one was later mobilized with a chemo-free regimen, the other required a bone marrow harvest. 34/39 (87%) of NDMM patients who completed leukapheresis underwent transplant at time of data cutoff: number of infused CD34+ cells was 4,85 x 106 CD34+/kg +/- 1,2 (mean +/- SD). All patients obtained stable neutrophils and platelets engraftments after a median of 12 days (range: 9-14) and 16 days (range: 13-25), respectively. No unexpected toxicities were reported.
Summary/Conclusion: Our data show that, after Dara-VTd, a mobilization regimen based on CTX 4 g/m2 and G-CSF allows the collection of high numbers of CD34+ cells and can be safely administered in the outpatient setting. CTX 4 g/m2 coupled with on-demand and patient-tailored usage of plerixafor is a valuable approach to achieve an optimal CD34+ cell collection after Dara-containing quadruplets, able to guarantee more than one autologous stem cell transplant and possible stem cell boosts in cases of prolonged cytopenia in subsequent therapies.
Keywords: Multiple myeloma, Induction, Stem cell mobilization, Cyclophosphamide