Sequence not salvage.

Chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of multiple myeloma (MM) has fundamentally changed the relapsed and refractory therapeutic landscape, but the disease remains incurable. Two CAR-T products, idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel, Carvykti), have been FDA- and EMA-approved for the treatment of relapsed/refractory MM (RRMM); both target B-cell maturation antigen (BCMA), a surface glycoprotein highly expressed on MM cells. Despite deep and durable responses following CAR-T therapy, most patients will need subsequent treatment, and the optimal next-line therapy is presently unclear. Commentary on: Liu et al. Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA-specific CAR-T therapy: A retrospective analysis of LEGEND-2. Br J Haematol 2024;204:1780-1789.

Mismatched related donor allogeneic haematopoietic cell transplantation compared to other donor types for Ph+ chronic myeloid leukaemia: A retrospective analysis from the Chronic Malignancies Working Party of the EBMT.

Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse-free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non-relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft-versus-host disease (GvHD)-free/relapse-free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.

Impact of newly diagnosed extramedullary myeloma on outcome after first autograft followed by maintenance: A CMWP-EBMT study.

BACKGROUND: No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy. METHODS: We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib. RESULTS: The median follow-up from maintenance start was 44 months. Three-year progression-free survival (PFS) was 52% (48%-57%) for no EMD, 56% (44%-69%) for paraskeletal involvement, and 45% (22%-68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three-year overall survival (OS) was 81% (77%-84%), 88% (80%-96%), and 68% (47%-89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD. CONCLUSION: Lenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start.

Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: A retrospective study by the chronic malignancies working party of the EBMT.

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for chronic phase (CP) chronic myeloid leukemia (CML) has dramatically decreased. Imatinib was the first TKI introduced to the clinical arena, predominantly utilized in the first line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with either a second or third generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2, or 3 TKI prior to allo-HCT for CP CML in 904 patients. A total of 323-, 371-, and 210 patients had 1, 2, or 3 TKI prior to transplant, respectively; imatinib (n = 778), dasatinib (n = 508), nilotinib (n = 353), bosutinib (n = 12), and ponatinib (n = 44). The majority had imatinib as first TKI (n = 747, 96%). Transplants were performed in CP1, n = 549, CP2, n = 306, and CP3, n = 49. With a median follow-up of 52 months, 5-year OS for the entire population was 64.4% (95% CI 60.9-67.9%), PFS 50% (95% CI 46.3-53.7%), RI 28.7% (95% CI 25.4-32.0%), and NRM 21.3% (95% CI 18.3-24.2%). No difference in OS, PFS, RI, or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p = ns). Significant factors influencing OS and PFS were > CP1 versus CP1 and Karnofsky performance (KPS) score > 80 versus ≤80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection.

Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: Changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019.

Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy-based induction fell significantly, being largely replaced by bortezomib-based regimens. The two-year complete response rate increased from 22% to 42%. The five-year progression-free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.

Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma.

There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.

Prognostic impact of early-versus-late responses to different induction regimens in patients with myeloma undergoing autologous hematopoietic cell transplantation: Results from the CALM study by the CMWP of the EBMT.

BACKGROUND: In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. METHOD: We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor). RESULTS: The length of induction treatment required to achieve a Good response did not affect PFS (P = .65) or OS (P = .61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (P = .31), and median OS 81.7, 92.7, and 77.4 months, respectively (P = .83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P-value = .02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post-transplant. CONCLUSION: The kinetics of response did not affect outcomes.

Standardised Reconstructed Skin Models in Toxicology and Pharmacology: State of the Art and Future Development.

Three-dimensional (3D) reconstructed human skin (RhS) models featuring fully-differentiated characteristics of in vivo human epidermis have been known for almost 40 years. In this chapter, the topic of commercial in vitro tissue models is described, taking RhS models as an example. The need for highly standardised models is evident for regulatory testing purposes, e.g. the classification and labelling of chemicals and formulations, as well as for pharmacology-oriented research and drug development. Following the standardisation of RhS model production by commercial developers, international validation studies and regulatory acceptance, 3D RhS models are now used globally in both industrial and academic research laboratories. Industrial production of standardised 3D RhS models involves GMP-compliant processes together with ISO 9001 documentation in order to control and ensure reproducibility and quality. Key biological, functional, and performance features that are addressed in industrial production include barrier properties, histological and immunohistochemical characterisation, lipid profile characterisation, and tissue viability before and after transport. An up-to-date survey of commercial RhS tissue producers and the regulatory acceptance status of major safety, hazard, and efficacy assays currently available to chemical and pharmaceutical industries is presented in this chapter. Safety and ethical concerns related to the use of human tissue in the industrial production of RhS models are discussed. Finally, innovative approaches to the production of standardised 3D RhS models including automated production, development of more representative 3D RhS models using advanced additive manufacturing tools, microfluidics technologies, and bioprinting are presented. The future outlook for 3D RhS models includes a prevalence of high-quality models which will be fabricated by end-users rather than commercial producers. These will overcome problems with shipments and customs clearance that many users still face when buying RhS from overseas commercial suppliers. Open-source technologies and commercial components for "do-it-yourself" RhS will significantly change the skin model market as well as regulatory acceptance of open-source models during the next decade. All of these developments and improvements will together allow more widespread use of in vitro RhS models for broader application as animal replacements in areas ranging from industrial and regulatory toxicology and pharmacology, to drug development and personalised medicine.

Are Autologous Stem Cell Transplants Still Required to Treat Myeloma in the Era of Novel Therapies? A Review from the Chronic Malignancies Working Party of the EBMT.

Melphalan at a myeloablative dose followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with myeloma. However, therapies such as new immunomodulatory drugs and proteasome inhibitors and, more recently, monoclonal antibodies and chimeric antigen receptor T cells are challenging the traditional role of ASCT. Which patients benefit from ASCT? Can its use be delayed until first relapse? The field is moving rapidly as novel agents lead to new patient care strategies. The place of ASCT in this changing landscape will be reviewed and reassessed.

Clinical data, limitations and perspectives on chimeric antigen receptor T-cell therapy in multiple myeloma.

PURPOSE OF REVIEW: Despite considerable therapeutic advances over the last decade, multiple myeloma remains an incurable disease. Novel treatment strategies are urgently needed. T cells can be genetically modified to express chimeric antigen receptors (CARs) targeting defined surface antigens on tumor cells. To date, over 90 clinical trials investigating the use of CAR T cells in multiple myeloma have been registered. RECENT FINDINGS: Although two CD19-directed CAR T-cell products have been approved, CD19 surface expression on plasma cells is limited or absent and CAR T-cell therapy in multiple myeloma is less advanced. B-cell maturation antigen (BCMA)-directed CAR T cells have shown promising efficacy and safety profiles in various phase I/II clinical trials. However, almost all treated patients continue to relapse. The current focus is therefore on strategies to overcome resistance mechanisms. These include the targeting of other surface antigens, refinements in T-cell signaling and dual-targeting approaches. SUMMARY: CAR T-cell therapy has finally moved into routine clinical use, the first experiments having taken place over 30 years ago. A BCMA-directed product for the treatment of multiple myeloma is expected to be approved shortly. However, further refinements of both CAR T-cell constructs and treatment protocols will be required to boost persistence, overcome resistance and reduce toxicities.

Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE).

Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

Conditioning-based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991-2012) on behalf of EBMT CMWP.

OBJECTIVES: The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma-reduced intensity conditioning (RIC), non-myeloablative (NMA), myeloablative conditioning (MAC) or Auto-AlloHCT-on outcomes in patients who had had a prior autologous transplant. METHODS: A retrospective analysis of the EBMT database (1991-2012) was performed. RESULTS: A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%-47%), 45% (95% CI 32%-57%), 19% (95% CI 6%-32%) and 34% (95% CI 17%-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276). CONCLUSION: From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.

The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma.

A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations. Regorafenib overcomes the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co-culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110δ inhibitor idelalisib. Most importantly, regorafenib significantly delays tumor growth in a xenograft mouse model of human MM. These results provide the rationale for further clinical evaluation of regorafenib, alone and in combination, in the treatment of MM.

Bortezomib for the treatment of multiple myeloma.

BACKGROUND: Multiple myeloma is a malignancy of plasma cells accounting for approximately 1% of cancers and 12% of haematological malignancies. The first-in-class proteasome inhibitor, bortezomib, is commonly used to treat newly diagnosed as well as relapsed/refractory myeloma, either as single agent or combined with other therapies. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effects of bortezomib on overall survival (OS), progression-free survival (PFS), response rate (RR), health-related quality of life (HRQoL), adverse events (AEs) and treatment-related death (TRD). SEARCH METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE (till 27 January 2016) as well as conference proceedings and clinical trial registries for randomised controlled trials (RCTs). SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared i) bortezomib versus no bortezomib with the same background therapy in each arm; ii) bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s) and iii) bortezomib dose comparisons and comparisons of different treatment administrations and schedules. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcomes data and assessed risk of bias. We extracted hazard ratios (HR) and their confidence intervals for OS and PFS and odds ratios (OR) for response rates, AEs and TRD. We contacted trial authors to provide summary statistics if missing. We estimated Logrank statistics which were not available. We extracted HRQoL data, where available. MAIN RESULTS: We screened a total of 3667 records, identifying 16 relevant RCTs involving 5626 patients and included 12 trials in the meta-analyses. All trials were randomised and open-label studies. Two trials were published in abstract form and therefore we were unable to assess potential risk of bias in full.There is moderate-quality evidence that bortezomib prolongs OS (four studies, 1586 patients; Peto OR 0.77, 95% CI 0.65 to 0.92) and PFS (five studies, 1855 patients; Peto OR 0.65, 95% CI 0.57 to 0.74) from analysing trials of bortezomib versus no bortezomib with the same background therapy in each arm.There is high-quality evidence that bortezomib prolongs OS (five studies, 2532 patients; Peto OR 0.76, 95% CI 0.67 to 0.88) but low-quality evidence for PFS (four studies, 2489 patients; Peto OR 0.67, 95% CI 0.61 to 0.75) from analysing trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s).Four trials (N = 716) examined different doses, methods of administrations and treatment schedules and were reviewed qualitatively only.We identified four trials in the meta-analysis that measured time to progression (TTP) and were able to extract and analyse PFS data for three of the studies, while in the case of one study, we included TTP data as PFS data were not available. We therefore did not analyse TTP separately in this review.Patients treated with bortezomib have increased risk of thrombocytopenia, neutropenia, gastro-intestinal toxicities, peripheral neuropathy, infection and fatigue with the quality of evidence highly variable. There is high-quality evidence for increased risk of cardiac disorders from analysing trials of bortezomib versus no bortezomib with different background therapy in each arm or versus other agents. The risk of TRD in either comparison group analysed is uncertain due to the low quality of the evidence.Only four trials analysed HRQoL and the data could not be meta-analysed.Subgroup analyses by disease setting revealed improvements in all outcomes, whereas for therapy setting, an improved benefit for bortezomib was observed in all outcomes and subgroups except for OS following consolidation therapy. AUTHORS' CONCLUSIONS: This meta-analysis found that myeloma patients receiving bortezomib benefited in terms of OS, PFS and response rate compared to those who did not receive bortezomib. This benefit was observed in trials of bortezomib versus no bortezomib with the same background therapy and in trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s). Further evaluation of newer proteasome inhibitors is required to ascertain whether these agents offer an improved risk-benefit profile, while more studies of HRQoL are also required.

Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).

Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1.

Stem Cell Mobilization Performed with Different Doses of Cytarabine in Plasma Cell Myeloma Patients Relapsing after Previous Autologous Hematopoietic Cell Transplantation-A Multicenter Report by the Polish Myeloma Study Group.

Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze the efficacy and safety of different doses of cytarabine (total 800 vs. 1600 vs. 2400 mg/m2) for remobilization. Sixty-five patients, 55% male, with a median age at remobilization 63 years, were included. Remobilization was performed with cytarabine_800 in 7, cytarabine_1600 in 36, and cytarabine_2400 in 22 patients. Plerixafor rescue was used in 25% of patients receiving cytarabine_1600 and 27% of those receiving cytarabine_2400. Patients administered cytarabine_800 were not rescued with plerixafor. Remobilization was successful in 80% of patients (57% cytarabine_800; 86% cytarabine_1600; 77% cytarabine_2400; p = 0.199). The yield of collected CD34+ cells did not differ between the different cytarabine doses (p = 0.495). Patients receiving cytarabine_2400 were at the highest risk of developing severe cytopenias, requiring blood product support, or having blood-stream infections. One patient died of septic shock after cytarabine_2400. In summary, remobilization with cytarabine is feasible in most patients. All doses of cytarabine allow for successful remobilization. Cytarabine_2400 is associated with higher toxicity; therefore, lower doses (800 or 1600 mg/m2) seem to be preferable.