Effect of different induction chemotherapy regimens on autologous hematopoietic stem cell mobilization in patients with multiple myeloma in the new drug era

Comparison Between Pegfilgrastim and Filgrastim-Based Autologous Hematopoietic Stem Cell Mobilization in the Setting of Patient Adapted (“Just in Time”) Plerixafor: Efficacy and Cost Analysis

Aim. To compare the efficacy of mobilization regimens (MR) differing in their composition and intensity, with the purpose of defining the criteria to personalize the choice of MR based on clinical and hematological characteristics of multiple myeloma (MM) patients.
 Materials & Methods. A retrospective analysis of the autologous hematopoietic stem cell (HSC) mobilization and autograft harvesting results was performed in 177 patients with newly diagnosed MM. The patients were divided into 4 groups. Group 1 included 62 patients with the median age of 53 years who were treated with single injection of cyclophosphamide (CF) dose 3 g/m2 as MR. Group 2 consisted of 71 patients with the median age of 58 years who received vinorelbine 35 mg/m2. Granulocyte colony-stimulating factor (G-CSF) as a monoregimen was administered to group 3 consisting of 33 patients with the median age of 55 years. Group 4 included 11 patients with the median age of 57 years who received G-CSF enhanced by plerixafor administration. G-CSF 10 µg/kg was used as MR. In all chemomobilization cases, daily G-CSF 10 µg/kg started on Day 4 from the administration of the chemotherapy drug prescribed as MR.
 Results. In the analyzed groups, the median time from MR start to the first leukocyte apheresis session was 11, 8, 5, and 5 days, respectively. On the first leukocyte apheresis day, the median CD34+ cell collection in group 3 was significantly lower than in groups 1, 2, and 4: 2.2 × 106/kg vs. 3.79 × 106/kg, 7.22 × 106/kg, and 3.9 × 106/kg, respectively. The total CD34+ cell collection after two leukocyte apheresis sessions was also the lowest in group 3 compared with groups 1, 2, and 4: 3.22 × 106/kg vs. 5.2 × 106/kg, 4.95 × 106/kg, and 7.5 × 106/kg, respectively. In the analyzed groups, the rate of mobilization with CD34+ cell collection < 2.0 × 106/kg was 6.5 %, 5.6 %, 18.2 %, and 9.1 %. The evaluation of the results in all patients showed a direct correlation of CD34+ cell collection with lenalidomide administered before autologous HSC mobilization. A significant difference in CD34+ cell collection in lenalidomide recipients vs. non-recipients was reported when vinorelbine as MR and G-CSF as monoregimen (р = 0.001 and р = 0.022, respectively) were used. No significant differences were observed either with CF or G-CSF combined with plerixafor treatment.
 Conclusion. Based on the findings, age of a MM patient, comorbidities, and prior lenalidomide administration can be regarded as key criteria for choosing one of 4 MRs.

Autologous Stem Cell Collection In Lymphoma and Myeloma Patients: Single Center Analysis With Intention To Successful Mobilization and Collection Under Restricted Permission For Use Of Plerixafor

Impact of Daratumumab on Hematopoietic Stem Cell Mobilization with G-CSF and on-Demand Plerixafor in Newly-Diagnosed Multiple Myeloma Patients

Motixafortide + G-CSF hematopoietic stem cell mobilization in patients with multiple myeloma following quadruplet induction therapy

Purpose The study aims to assess the clinical efficacy and safety profile of plerixafor in combination with polyethylene glycolated recombinant human granulocyte colony-stimulating factor (PEGylated rhG-CSF) for autologous hematopoietic stem cell (auto-HSC) mobilization in Chinese patients diagnosed with multiple myeloma (MM). Methods A retrospective analysis was conducted to evaluate the stem cell collection efficiency, post-transplant hematopoietic reconstitution, and mobilization-related adverse events in a cohort of 18 MM patients who underwent stem cell mobilization using the combination of plerixafor and PEGylated rhG-CSF. Successful mobilization was defined as achieving or surpassing a threshold of 2.0×106/kg. An excellent mobilization is characterized by achieving a yield of at least 5.0×106/kg. Results Our results revealed an overall stem cell collection success rate of 100%. Notably, 72% of patients achieved successful mobilization within the first day. Furthermore, the overall excellent collection rate was 56%, with a 1-day excellent collection rate of 27%. The median number of collected CD34 + cells was 5.62(2-16.19)×106/kg. The most frequently encountered adverse events were bone pain (11%), nausea and vomiting (11%), and diarrhea (11%), all classified as grade 1–2. All patients underwent auto-HSC transplantation, with a median engraftment time of 11 (ranging from 9 to 14) days for neutrophils and 14 (ranging from 10 to 20) days for platelets, respectively. Conclusion In conclusion, this is the first report of the combination of PEGylated rhG-CSF and plerixafor for auto-HSC mobilization and collection in Chinese patients with MM, and the results show good mobilization success rate and safety.

AIM. To compare the efficacy and toxicity of various regimens of autologous hematopoietic stem cell (HSC) mobilization (cytarabine + G-CSF, cyclophosphamide + G-CSF, and plerixafor + G-CSF) in hematologic malignancy patients with predicted poor HSC collection. MATERIALS & METHODS. This retrospective study compared the results of autologous HSC mobilization in peripheral blood of 87 hematologic malignancy patients with predicted poor collection. Out of them, 36 patients received cytarabine 400 mg/m2/12 h IV on Day 1 and Day 2 combined with G-CSF 10 µg/kg SC from Day 5 to the last apheresis. In 18 patients, to mobilize autologous HSCs, cyclophosphamide 2–4 g/m2 IV on Day 1 + G-CSF 10 µg/kg SC also from Day 5 were used. The third regimen of autologous HSC mobilization (n = 33) started with G-CSF 10 µg/kg/day SC on Days 1, 2, 3, 4, and 5, and plerixafor 0.24 µg/kg/day SC was administered on Day 5. The analysis focused on the data from 27 classical Hodgkin lymphoma (cHL), 44 non-Hodgkin lymphoma (NHL), and 16 multiple myeloma patients. The median age was 48, 33, and 55 years, respectively. RESULTS. The median CD34+ cell collection was 8.1 × 106/kg body mass in cytarabine + G-CSF recipients vs. 6.5 × 106/kg in cyclophosphamide + G-CSF and 2.8 × 106/kg in plerixafor + G-CSF recipients (p < 0.0001). Most common complications were thrombocytopenia grade 4 (in 44 % of cytarabine + G-CSF and 6 % of cyclophosphamide + G-CSF recipients; p = 0.004) and neutropenia grade 4 (in 42 % of cytarabine + G-CSF and 22 % of cyclophosphamide + G-CSF recipients; p = 0.23). CONCLUSION. Cytarabine + G-CSF mobilization of autologous HSCs can well be considered to be an effective and safe regimen for cHL and NHL predicted poor mobilizers. This conclusion, however, does not apply, for a number of reasons, to plasma cell tumor patients. For this category, the determination of an optimal autologous HSC mobilization regimen still remains a highly relevant issue.

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma. The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection. A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection. Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.

Clinical Study on the Efficacy and Safety of Peg Rhg CSF for Autologous Hematopoietic Stem Cell Mobilization in Lymphoma and Multiple Myeloma：a Randomized Controlled, Multicenter Clinical Study

Feasibility of Hematopoietic Stem Cell Collection and Cryopreservation in Waldenstrom's Macroglobulinemia

High-dose melphalan plus autologous stem cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem cell (HSC) collection is crucial to ensure hematologic recovery after ASCT. In this prospective, observational study we evaluated HSC mobilization with granulocyte colony-stimulating factor (G-CSF), cyclophosphamide, and ‘on-demand’ plerixafor (in patients with <20×106 CD34+ cells/L after at least 4 days of G-CSF or failing to collect ≥1×106 CD34+ cells/kg after the first apheresis) in NDMM patients treated with novel agent-based induction therapy. The primary endpoint was the rate of poor mobilizers (patients collecting <2×106 CD34+ cells/kg or requiring plerixafor rescue to reach an adequate HSC harvest). Secondary endpoints included the rate of patients collecting ≥2×106 CD34+ cells/kg after plerixafor administration and the identification of factors predicting mobilization failure or plerixafor need. Overall, 301 patients (median age 60 years) were enrolled. Two hundred and eighty-seven of 301 (95%) and 274 of 301 (93%) patients collected ≥2×106 and ≥4×106 CD34+ cells/kg, respectively, with a median of 9.9×106 CD34+ cells/kg collected. Poor mobilizers were 48 of 301 (16%): 34 of 301 (11%) required plerixafor rescue, and 14 of 301 (5%) failed HSC collection regardless of plerixafor. Thirty-four of 38 (90%) patients receiving plerixafor collected ≥2×106 CD34+ cells/kg. Bone marrow plasmacytosis at diagnosis >60% (odds ratio [OR]=4.14), lenalidomide use (OR=4.45), and grade 3-4 hematologic toxicities during induction (OR=3.53) were independently associated with a higher risk of mobilization failure or plerixafor need. Cyclophosphamide plus G-CSF and ‘on-demand’ plerixafor is an effective strategy in NDMM patients treated with novel agents, resulting in a high rate of HSC collection and high HSC yield (clinicaltrials gov. identifier: NCT03406091).

Objective: To review the pharmacology, pharmacokinetics, dosage, administration, clinical efficacy, safety, and place in therapy of plerixafor, a CXCR4 receptor antagonist used to mobilize stem cells prior to hematopoietic stem cell transplantation. Data Sources: Articles were identified by searching MEDLINE (1950-August 2009) and the American Society of Hematology abstract database using the key terms plerixafor, AMD3100, hematopoietic stem cell transplant, mobilization, multiple myeloma, and non-Hodgkin's lymphoma. Additional articles were obtained by using the reference sections of articles found during the literature search. Study Selection and Data Extraction: All articles identified from the literature search were reviewed for relevant information. Appropriate information was included in this review. The search was restricted to available English-language articles, including those on both preclinical and clinical trials. Data Synthesis: Plerixafor is a CXCR4 receptor antagonist approved by the FDA to assist in the mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma or multiple myeloma undergoing autologous stem cell transplant. Plerixafor is used in combination with granulocyte colony-stimulating factor. Plerixafor has been compared with placebo in both Phase 2 and Phase 3 clinical trials and has been shown to allow for a greater collection of hematopoietic stem cells in fewer apheresis sessions. Plerixafor demonstrated good tolerability in clinical trials. Conclusions: Plerixafor has demonstrated efficacy and tolerability when used for stem cell mobilization in patients with non-Hodgkin's lymphoma and multiple myeloma. Further studies are warranted to determine the safety and efficacy of plerixafor in patients with malignancies other than non-Hodgkin's lymphoma or multiple myeloma who are undergoing stem cell transplant and to determine its potential use in healthy stem cell donors.

Intensive chemotherapy and autologous hematopoietic stem cell mobilization, collection and transplantation with simultaneous Imatinib therapy in patients with blast crisis chronic myeloid leukaemia

Introduction Although plerixafor in association with granulocyte colony-stimulating factor (G-CSF) can improve mobilization and collection of hematopoietic stem cells (HSC) by leukapheresis, cost may limit its clinical application. The present study systematically reviews economic evaluations of plerixafor plus G-CSF usage compared to G-CSF alone and compares different strategies of plerixafor utilization in multiple myeloma and lymphoma patients eligible for autologous HSC transplantation. Areas covered Relevant economic evaluations, partial or complete, were searched on PubMed, Embase, LILACS, and Cochrane Central Register of Controlled Trials for a period ending 30 June 2021. This systematic review was reported following the PRISMA Statement. Six economic evaluations were included, considering the use of upfront or just-in-time plerixafor compared to G-CSF alone or other plerixafor strategies. Most comparisons showed both increased cost and health benefits with the addition of plerixafor. Most analyses favored just-in-time plerixafor compared to upfront plerixafor, with a probable preference for broader cutoffs for just-in-time plerixafor initiation. Expert opinion Plerixafor is a potentially cost-effective technology in the mobilization of HSC in patients with multiple myeloma and lymphomas eligible for autologous HSC transplantation. There is a decreased number of leukapheresis sessions and remobilizations and a higher yield of CD34+ cells.