Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

INTRODUCTION: There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy-autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting. METHODS: A total of 449 consecutive patients were included in this retrospective analysis. RESULTS: No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m2, or estimated glomerular filtration rate < 60 mL/min/1.73 m2 when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups. CONCLUSION: For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.

Fever Characteristics and Impact on Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy.

BACKGROUND: Fever is a hallmark symptom of cytokine release syndrome (CRS) after chimeric antigen receptor (CAR) T-cell therapy. Fever characteristics and the impact of fever on safety and efficacy post CAR T are not well understood. We sought to explore the impact of fever and its characteristics on safety and efficacy post CAR T-cell therapy. PATIENTS AND METHODS: We reviewed 40 patients with various hematologic malignancies (non-Hodgkin lymphoma, acute lymphoblastic leukemia, multiple myeloma) treated with CAR T-cell therapy between March 2019 and March 2022. We evaluated all patients who developed fever after CAR T infusion and analyzed the association of fever with toxicity (CRS and neurotoxicity) and efficacy (overall response (ORR) and complete response (CR) at day +90 post CAR T infusion). Fever was defined as per Lee criteria (equal to or greater than 38°C). CRS and immune-effector cell associated neurotoxicity syndrome (ICANS) were graded using American Society for Transplantation and Cellular Therapy grading system. RESULTS: Fever occurred in 75% (30/40) of patients. Rates of all grade and grade 3+ CRS and ICANS were 75%, 2%, 33% and 10%, respectively. Fever occurred within 24 and 72 hours after CAR T infusion in 40% and 53% of patients, respectively. Fifty percent of patients received tocilizumab (toci) for CRS. After the first dose of toci, fever recurred in 38% of the patients, of which 67% had recurrence within 24 hours. Day +90 CR rates were 43% and 10% in patients with and without fever, respectively (Table 3). CONCLUSION: While fever is common after CAR T-cell therapy, early-onset and higher magnitude do not appear to affect safety or efficacy of CAR T. Absence of fever may affect response to CAR T.

Similar dynamics of intraapheresis autologous CD34+ recruitment and collection efficiency in patients undergoing mobilization with or without plerixafor.

BACKGROUND: Compared with growth factor (G) alone, the combination of G with plerixafor (G + P) increases peripheral blood CD34+ count (PB-CD34+) and improves CD34+ collection yield (yCD34+) in multiple myeloma and lymphoma patients undergoing autologous hematopoietic progenitor cell (AHPC) mobilization. It is unknown whether the improved yCD34+ with G + P results entirely from expansion of PB-CD34+ or also from increased intraapheresis CD34+ recruitment and collection efficiency. STUDY DESIGN AND METHODS: We retrospectively studied 192 patients who underwent AHPC mobilization and collection with G (n = 73) or G + P (n = 119) to compare the adjusted relative efficiency (aRE), the proportion of the circulating CD34+ pool that is captured for each blood volume processed. Additionally, in a prospective cohort of nine patients mobilizing with G and 11 with G + P, PB-CD34+ after leukapheresis allowed calculation of the recruitment coefficient (RC), proportion of the initial CD34+ pool recruited from the marrow into peripheral blood for each blood volume processed. RESULTS: There was no difference in aRE between G and G + P (0.50 vs. 0.46; p = 0.37) and no substantial decline in aRE with higher blood volumes processed in either group. RC was also not different between G and G + P (median, 0.39 and 0.38, respectively; p = 0.7). Prediction of yCD34+ was determined essentially by PB-CD34+ and not affected independently by plerixafor. CONCLUSION: Kinetics of intraapheresis CD34+ recruitment and collection is proportional to PB-CD34+ but not influenced further by plerixafor.

Pegfilgrastim- versus filgrastim-based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis.

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight-based FIL with flat-dose pegfilgrastim (PEG) in a validated cost-based mobilization algorithm for patient-adapted use of plerixafor would add convenience without increased cost. STUDY DESIGN AND METHODS: A single-center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12-mg flat dose of PEG. Peripheral blood CD34+ cells (PB-CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target-specific threshold of PB-CD34+ started apheresis immediately while subjects with lower PB-CD34+ received plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB-CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1×10(6) vs. 28.7×10(6)cells/L, p=0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p=0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor.