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B Introduction: b Patients (pt) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), especially those with progression on Bruton tyrosine kinase inhibitors (BTKi) and venetoclax failure, have limited treatment options and poor pt-reported outcomes (PRO)/health-related quality of life (HRQOL). Health-related quality of life in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with liso-cel in TRANSCEND CLL 004 The CD19-directed chimeric antigen receptor T cell therapy lisocabtagene maraleucel (liso-cel) is being evaluated in R/R CLL/SLL in the phase 1/2 TRANSCEND CLL 004 study (NCT03331198). [Extracted from the article]

LISOCABTAGENE MARALEUCEL (LISO-CEL) IN R/R CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): PRIMARY ANALYSIS OF TRANSCEND CLL 004 B Introduction: b Achieving durable CR with current treatment is uncommon in patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based treatment. Keyword: cellular therapies B Conflicts of interests pertinent to the abstract b B T. Siddiqi b Consultant or advisory role: Astra Zeneca, BMS, Celgene, Kite pharma, Beigene, Abbvie Research funding: Astra Zeneca, BMS, Celgene, Oncternal, Ascentage pharma, Kite pharma, TG therapeutics, Pharmacyclics, Juno therapeutics Other remuneration: Speaker's Bureau: Astra Zeneca, BMS, Beigene B D. G. Maloney b Consultant or advisory role: A2 Biotherapeutics, Member of the Scientific Advisory Board GRAPH Navan Technologies, Member of the Scientific Advisory Board GRAPH Chimeric Therapeutics, Member of the Scientific Advisory Board GRAPH Genentech, Member and Chair of the Lymphoma Steering Committee GRAPH BMS, Member of the JCAR017 EAP-001 Safety Review Committee GRAPH BMS, Member, CLL Strategic Council GRAPH ImmPACT Bio, Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program GRAPH Gilead Sciences, Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies GRAPH Interius. [Extracted from the article]

Importance: Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year., Observations: Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients., Conclusions and Relevance: Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

Since the introduction of lenalidomide into induction therapy for multiple myeloma (MM), there have been conflicting reports about its impact on autologous peripheral blood stem cell (PBSC) mobilization. We evaluated the impact of previous lenalidomide exposure in a large cohort of patients with MM undergoing mobilization and collection at a tertiary stem cell transplantation center. We hypothesized that collection of PBSCs is feasible even with a prolonged duration of previous lenalidomide therapy. We examined patients with MM who attempted stem cell mobilization and collection, seen at our center between January 2012 and July 2015. The patients were categorized into 3 groups for analysis: (1) patients with previous receipt of >6 cycles lenalidomide, (2) patients with previous receipt of ≤6 cycles of lenalidomide, and (3) patients without previous lenalidomide exposure. We compared collection yields and days of apheresis among the 3 groups using linear regression analysis. We identified 297 patients with MM who underwent mobilization of PBSCs. Of these, 35 had received >6 cycles of lenalidomide (median, 8 cycles; range, 7 to 25 cycles), 156 had received ≤6 cycles of lenalidomide (median, 4 cycles; range, 1 to 6 cycles), and 106 had received no lenalidomide. Prior lenalidomide exposure did not have a statistically significant impact on the absolute number of CD34 + cells collected or on the duration of collection based on a multivariate linear regression analysis for association between receipt of >6 cycles of lenalidomide. In this retrospective analysis of MM patients undergoing autologous PBSC transplantation, we show that the duration of previous lenalidomide exposure does not impact the total number of PBSCs collected or the number of days of apheresis. These data suggest that longer courses of induction therapy with lenalidomide-containing regimens to achieve a maximum response can be safe without impairing the ability to collect PBSCs, and that limiting lenalidomide use before mobilization does not appear warranted in all cases., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Bortezomib has been incorporated into thalidomide and dexamethasone provided with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE) as an intensive regimen before autologous stem-cell transplantation for multiple myeloma (MM). We examined MM patients at our center who received chemomobilization with a regimen that substituted carfilzomib and lenalidomide for bortezomib and thalidomide (KRD-PACE)., Patients and Methods: This was a retrospective study of 27 MM patients who received KRD-PACE for chemomobilization. Our analysis included patients who had circulating plasma cells (CPCs) by flow cytometry, ≥ 10% bone marrow plasma cells (BMPC), a monoclonal protein ≥ 1 g/dL, or an involved serum free light chain ≥ 10 mg/dL., Results: The most common indication for KRD-PACE was BMPC ≥ 10% in 16 patients (60%), followed by CPCs in 11 (41%). The median (range) age was 61 (35-69) years, and the median (range) BMPC before treatment was 10% (5%-47%). The overall response rate was 43%, and a median (range) of 20.24 (8.08-69.88) × 10 6 CD34 + cells/kg were collected. CPC clearance rate was 50%, and the median reduction in BMPC was 75%. Two patients had sinus bradycardia and 5 (19%) had neutropenic fever., Conclusion: KRD-PACE is an effective therapy to mobilize peripheral blood stem cells in MM patients with residual disease burden. This regimen was successful at clearing CPCs and reducing BMPC burden, with an overall response rate of 43%. Despite theoretical concern regarding the combination of 3 cardiotoxic agents, we observed a low frequency of cardiac issues., (Published by Elsevier Inc.)

Engraftment syndrome (ES) is a known complication of autologous hematopoietic stem cell transplant during neutrophil recovery. There is a limited amount of data available comparing the incidence of ES with post-transplant granulocyte colony-stimulating factor versus granulocyte macrophage colony-stimulating factor (GM-CSF), specifically in patients with multiple myeloma. Our retrospective review of 156 patients at a single center showed that GM-CSF was associated with a higher incidence of ES compared with G-CSF (32% versus 8% of patients, P < .001) and that development of ES was associated with a 32.9% (P < .001) longer hospital stay. This suggests that the choice of growth factor could possibly contribute to the development of ES and the associated costs of increased medical care., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is an effective treatment modality for immunoglobulin light-chain (AL) amyloidosis; however, its application remains restricted to patients with good performance status and limited organ involvement. In recent years, the paradigm for AL amyloidosis has changed with the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). We hypothesized that use of novel agent induction regimens has improved outcomes for patients with AL amyloidosis undergoing HDM/SCT at our center., Methods: All patients with AL amyloidosis, age ≥18 years who underwent HDM/SCT between 2001 and 2014 at the Fred Hutchinson Cancer Research Center and University of Washington Medical Center were included in this study. Any regimen administered within 6 months prior to HDM/SCT including an IMiD or a PI was considered a novel induction regimen. Use of induction regimen was evaluated in a Cox proportional hazard model for association with progression-free survival (PFS) and overall survival (OS)., Results: Forty-five patients with AL amyloidosis underwent HDM/SCT. The median age was 57.2 years (range 39-74.4), 15 (33.3%) were women. The median number of organs involved was 2 (range 1-5), with 20 patients having only 1 (44.4%), 10 patients having 2 (22.2%), and 15 patients (33.3%) having ≥ 3 organs involved. Novel agent induction regimens were used prior to HDM/SCT in 21 patients (46.7%); these comprised PI in 13/21 (57.1%), IMiD alone in 6/21 (28.6%), PI and cyclophosphamide (CyBorD) in 3/21 (14.3%), and IMiD and PI in 3/21 (14.3%). Use of a novel agent induction regimen was associated with improved, but not OS. The 3-year PFS for patients who received a novel agent induction was 79%, while for those who did not was 53% (hazard ratio [HR] = 0.317, p = 0.048). The 3-year OS for patients who received novel agent induction regimens was 95%, while for those who did not was 71% (HR = 0.454, p = 0.247)., Discussion: Our data suggest that use of a novel agent induction regimen including an IMiD or PI prior to HDM/SCT for patients with AL amyloidosis could improve outcomes, with improvement in PFS. Although these results are limited by sample size and lack of randomization, these results support possible further investigation of novel agent induction regimens in the context of a prospective clinical trial., Competing Interests: Declaration of interest The authors report no conflicts of interest. This work was supported by research funding from National Institutes of Health [grant number K24CA184039] and philanthropic gifts from Frank and Betty Vandermeer.

Mucormycosis is rare, presenting as breakthrough infection among haematological and transplant patients on prophylaxis with voriconazole. We report an unusual presentation of this infection, that which is pneumonia progressing to cardiac arrest. A 68-year-old woman with refractory acute myelogenous leukaemia on voriconazole prophylaxis was initially admitted for neutropenic fever and pneumonia. She was discharged improved on antibiotics and voriconazole for presumed aspergillosis. She returned after 1 month with the same presentation. She eventually improved on antibiotics and voriconazole, and eventually received bone marrow transplantation. Three days later, she developed pleuritic chest pain, dyspnoea, and hypoxia requiring intubation. An hour after intubation, the patient arrested and expired. Autopsy revealed Rhizopus pneumonitis with pulmonary infarction, and emboli to her cerebellum, heart, thyroid and kidney. Mucormycosis is an emerging, fatal infection that should be suspected in haematological and transplant patients who deteriorate on voriconazole., (2014 BMJ Publishing Group Ltd.)