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Background: Patients with prior allogeneic stem cell transplant (alloSCT) are typically excluded from trials of chimeric antigen receptor (CAR) T cell therapies, because their engineered cells may include allogeneic T cells. Ciltacabtagene autoleucel (cilta-cel) demonstrated early, deep, durable responses and manageable safety in heavily pretreated relapsed/refractory multiple myeloma patients. We retrospectively analyzed patients who received alloSCT prior to cilta-cel in CARTITUDE-1., Patients and Methods: Patients eligible for CARTITUDE-1 were ≥18 years, had ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody. Patients with active graft-versus-host disease (GVHD) or had alloSCT within 6 months before apheresis were excluded. Patients received cilta-cel 5 to 7 days after lymphodepletion., Results: Patients (N = 7) received median 9 prior LOTs (range, 6-14); median time since alloSCT was 5.1 years (range, 2.7-6.2). At median follow-up 27.7 months after cilta-cel infusion, overall response rate was 85.7% (n = 6). The safety profile was generally consistent with patients without alloSCT as prior therapy (cytokine release syndrome, 85.7% vs. 95.6%, respectively; immune effector cell-associated neurotoxicity syndrome, 14.3% vs. 16.7%). One patient with prior alloSCT had grade 3 movement and neurocognitive treatment-emergent adverse events/parkinsonism. No GVHD cases were reported. Two patients died due to adverse events (treatment-related lung abscess; unrelated liver failure)., Conclusion: Cilta-cel efficacy and safety were comparable between CARTITUDE-1 patients with and without prior alloSCT. Additional studies are needed to fully elucidate the suitability of CAR-T cell therapy in the post-alloSCT setting., Competing Interests: Disclosure M. Htut consulted and served on advisory committees for and received travel funding from Millennium; and received research funding from Judy and Bernard Briskin Center for Multiple Myeloma Research (Inst) and BMS (Inst). B. Dhakal consulted and served on advisory committees for Amgen, Takeda, Janssen, GlaxoSmithKline, Natera, and Sanofi; received honoraria from Celgene, Karyopharm Therapeutics, Sanofi, and GlaxoSmithKline; and received research funding from Amgen, Janssen, and GlaxoSmithKline. A.D. Cohen consulted and served on advisory committees for Celgene, Janssen Oncology, Oncopeptides, Takeda, Seattle Genetics, GlaxoSmithKline, Novartis, Bristol-Myers Squibb, AstraZeneca, and Roche/Genentech; received research funding from Novartis (Inst) and GlaxoSmithKline (Inst); has patents related to CAR-T cells and biomarkers of cytokine release syndrome; has given expert testimony for Janssen Oncology; and received travel funding from GlaxoSmithKline, Takeda, Celgene, and Janssen Oncology. T. Martin consulted and served on advisory committees for GlaxoSmithKline and Legend Biotech USA Inc. and received research funding from Sanofi (Inst), Amgen (Inst), and Janssen Oncology (Inst). J.G. Berdeja consulted and served on advisory committees for Takeda (Inst), Bristol-Myers Squibb (Inst), CRISPR Therapeutics (Inst), Celgene (Inst), Kite, a Gilead company (Inst), Janssen (Inst), Legend Biotech (Inst), Secura Bio (Inst), and Bluebird Bio (Inst); and received research funding from Celgene (Inst), Takeda (Inst), Bristol-Myers Squibb (Inst), Amgen (Inst), Janssen (Inst), Novartis (Inst), AbbVie (Inst), Bluebird Bio (Inst), Teva (Inst), Genentech/Roche (Inst), Poseida Therapeutics (Inst), Sanofi (Inst), Acetylon Pharmaceuticals (Inst), Lilly (Inst), Celularity (Inst), CRISPR Therapeutics (Inst), EMD Serono (Inst), Ichnos Sciences (Inst), GlaxoSmithKline (Inst), and Incyte (Inst). S.Z. Usmani consulted and served on advisory committees for Celgene, Amgen, Janssen Oncology, Seattle Genetics, Takeda, GlaxoSmithKline, Karyopharm Therapeutics, AbbVie, SkylineDx, Merck, Oncopeptides, Genentech, Gilead Sciences, and Bristol-Myers Squibb/Celgene; served on speakers’ bureaus for Takeda, Amgen, Janssen Oncology, Sanofi, and Bristol-Myers Squibb/Celgene; and received research funding from Celgene, Array BioPharma, Janssen Oncology, Pharmacyclics, Sanofi, Bristol-Myers Squibb, Amgen, Seattle Genetics, Merck, SkylineDx, and GlaxoSmithKline. M. Agha owns stock in GenCART, Inc. D. Madduri is employed by Janssen Oncology; owns stock in Roivant; and consulted and served on advisory committees for Takeda, Janssen Oncology, Celgene, Legend Biotech USA Inc., GlaxoSmithKline, and Foundation Medicine. C.C. Jackson is employed by Janssen and owns stock in Janssen; and served as a consultant physician for Memorial Sloan Kettering Cancer Center. W. Deraedt, T.-m. Yeh, and X. Xu are employed by and own stock in Janssen. E. Zudaire is employed by, owns stock in, received travel funding from, and has patents pending with Janssen. L. Pacaud is employed by and owns stock in Legend Biotech USA Inc. M. Akram is employed by Legend Biotech USA, Inc. S. Jagannath consulted and served on advisory committees for Bristol-Myers Squibb, Janssen, Karyopharm Therapeutics, Legend Biotech USA Inc., Takeda, and Sanofi; and received travel funding from Bristol-Myers Squibb and Janssen., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Multiple myeloma is a hematologic malignancy that is typically associated with recurrent relapses. There are numerous frontline treatment regimens that are highly effective for individual patients. The introduction of anti-CD38 monoclonal antibody therapy has shifted treatment decision-making in this setting, with many centers now considering the use of daratumumab as part of initial therapy regardless of patient eligibility for autologous stem cell transplantation (ASCT). Daratumumab has demonstrated clinical efficacy and acceptable toxicity in the first and later lines of therapy, increasing complexity in treatment selection and sequencing. Although daratumumab-containing regimens may not be appropriate for every patient, it is increasingly recognized that the most effective regimens should be used upfront, as high rates of attrition mean that many patients in real-world practice may see a limited number of lines of therapy., Methods: A panel of experts in multiple myeloma was convened to consider current evidence and treatment practices to inform a series of consensus statements on the optimal management of newly diagnosed multiple myeloma, including not only treatment selection, but the need for infection prophylaxis, route of administration, and mitigation of potential infusion-related reactions, among other clinical challenges., Results/conclusions: The goal of the present review article is to encapsulate these consensus statements and the rationale for their development, which altogether may help inform treatment selection and clinical decision-making in the front line., (Copyright © 2023. Published by Elsevier Inc.)

Autologous stem cell transplantation (ASCT) is a standard of care treatment for patients with multiple myeloma (MM). However, only 20% to 30% of patients with MM for whom the procedure is indicated undergo ASCT. Barriers to ASCT may be informational, financial, logistic, or cultural and may affect patients and treating oncologists. Available and accessible accurate ASCT-related information is essential to overcome these barriers. Such resources can be created by blood and marrow transplantation societies and patient advocacy groups, ideally in collaboration with MM specialists at transplant centers. An umbrella office at the society level is also recommended to connect oncologists, advocacy groups, and transplantation specialists; provide informational resources to patients; and conduct research into region- and population-specific barriers to ASCT., (Copyright © 2023. Published by Elsevier Inc.)

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem cell mobilization yields, apheresis attempts, and engraftment outcomes for patients from each study. Adult transplantation-eligible patients with NDMM received induction therapy consisting of daratumumab plus carfilzomib/lenalidomide/dexamethasone (D-KRd) for four 28-day cycles in the single-arm MASTER trial or lenalidomide/bortezomib/dexamethasone (RVd) with or without daratumumab (D) for four 21-day cycles in the randomized GRIFFIN trial, followed by stem cell mobilization and ASCT in both studies. Institutional practice differed regarding plerixafor use for stem cell mobilization; the strategies were upfront (ie, planned plerixafor use) or rescue (ie, plerixafor use only after mobilization parameters indicated failure with granulocyte colony-stimulating factor [G-CSF] alone). Descriptive analyses were used to summarize patient characteristics, stem cell mobilization yields, and engraftment outcomes. In MASTER, 116 D-KRd recipients underwent stem cell mobilization and collection at a median of 24 days after completing induction therapy. In GRIFFIN, 175 patients (D-RVd, n = 95; RVd, n = 80) underwent mobilization at a median of 27 days after completing D-RVd induction therapy and 24 days after completing RVd induction therapy. Among those who underwent mobilization and collection, 7% (8 of 116) of D-KRd recipients, 2% (2 of 95) of D-RVd recipients, and 6% (5 of 80) of RVd recipients did not meet the center-specific minimally required CD34 +  cell yield in the first mobilization attempt; however, nearly all collected sufficient stem cells for ASCT on remobilization. Among patients who underwent mobilization, plerixafor use, either upfront or as a rescue strategy, was higher in patients receiving D-KRd (97%; 112 of 116) and D-RVd (72%; 68 of 95) compared with those receiving RVd (55%; 44 of 80). The median total CD34 +  cell collection was 6.0 × 10 6 /kg (range, 2.2 to 13.9 × 10 6 /kg) after D-KRd induction, 8.3 × 10 6 /kg (range, 2.6 to 33.0 × 10 6 /kg) after D-RVd induction, and 9.4 × 10 6 /kg (range, 4.1 to 28.7 × 10 6 /kg) after RVd induction; the median days for collection were 2, 2, and 1, respectively. Among patients who underwent mobilization, 98% (114 of 116) of D-KRd patients, 99% (94 of 95) of D-RVd patients, and 98% (78 of 80) of RVd patients underwent ASCT using median CD34 +  cell doses of 3.2 × 10 6 /kg, 4.2 × 10 6 /kg, and 4.8 × 10 6 /kg, respectively. The median time to neutrophil recovery was 12 days in all 3 treatment groups across the 2 trials. Because both trials used different criteria to define platelet recovery, data on platelet engraftment using the same criteria are not available. Four cycles of daratumumab- and lenalidomide-based quadruplet induction therapy had a minimal impact on stem cell mobilization and allowed predictable stem cell harvesting and engraftment in all patients who underwent ASCT. Upfront plerixafor strategy may be considered, but many patients were successfully collected with the use of G-CSF alone or rescue plerixafor., Competing Interests: Conflict of interest statement SC received honoraria from GlaxoSmithKline, Omeros, and Sanofi and institutional research funding from Janssen, Amgen, Sanofi, Bristol Myers Squibb, Allogene, Ionis, Novartis, Syndax, and GlaxoSmithKline, and is co-chair of the SWOG S1803 clinical trial. NLW received consulting fees from Bristol Myers Squibb and holds stock in Gilead. LJC served as a consultant and received honoraria from Amgen, Janssen, Bristol Myers Squibb, Karyopharm, Pfizer, and Sanofi; received research funding from Amgen, Janssen, and Bristol Myers Squibb; and served on speakers bureaus for Amgen and Sanofi. JLK served as a consultant for Genentech, AbbVie, Janssen, Incyte, Celgene, Bristol Myers Squibb, Roche/Genentech, and Tecnopharma; received research funding from Genentech, AbbVie, Janssen, Amgen, Fortis Therapeutics, Heidelberg Pharma, Novartis, Sutro Biopharma, and Takeda; received honoraria from Tecnopharma, AbbVie, Janssen, Roche/Genentech, and Tecnopharma; and held membership on an entity's board of directors or advisory committees for Incyte and TG Therapeutics. DWS served as a consultant for GlaxoSmithKline, Janssen, and Sanofi; and served as a consultant and held membership on an entity's board of directors or advisory committees for Janssen and AbbVie. BR received honoraria from Incyte, Takeda, and PharmaEssentia; served as a consultant for PharmaEssentia; and served on a speakers bureau for Bristol Myers Squibb. CR served as a consultant and on speakers bureaus for Bristol Myers Squibb, Janssen, Takeda, Amgen, and Karyopharm; and received honoraria and served as a consultant for Oncopeptides. AC served as a consultant and held membership on an entity's board of directors or advisory committees for Janssen Oncology, Bristol Myers Squibb/Celgene, Amgen, Karyopharm, Sanofi Genzyme, Oncopeptides, GlaxoSmithKline, Secura Bio, Shattuck Labs, Genentech, AbbVie, and Antengene; served as a consultant for Takeda, Novartis, and Millennium/Takeda; held membership on an entity's board of directors or advisory committee for Seattle Genetics; and received research funding from Janssen Oncology, Bristol Myers Squibb/Celgene, Amgen, Takeda, Seattle Genetics, Novartis, Pharmacyclics, and Millennium/Takeda. RS held membership on an entity's board of directors or advisory committees for Sanofi Genzyme and Janssen Pharmaceuticals and received research funding from Sanofi Genzyme. LDA served as a consultant, received honoraria, held membership on an entity's board of directors or advisory committee, and received research funding from Celgene, Bristol Myers Squibb, Janssen, GlaxoSmithKline, Karyopharm, Oncopeptides, AbbVie, BeiGene, Prothena, and Amgen. SB received grants from Amyloid Foundation and honoraria from Adaptive Biotechnology. BD served as a consultant for Janssen, Sanofi, Genentech, and AbbVie; received honoraria from Bristol Myers Squibb, GlaxoSmithKline, Sanofi, Karyopharm, and Janssen; and served on an advisory board for Janssen, Natera, Arcellx Takeda, Amgen, and Sanofi. NS served as a consultant for Amgen, CareDx, CSL Behring, GlaxoSmithKline, Indapta Therapeutics, Karyopharm, Kite, Oncopeptides, and Sanofi; and received research funding from bluebird bio, Bristol Myers Squibb/Celgene, Janssen, Nektar, Poseida, Precision BioSciences, Sutro Biopharma, and TeneoBio. NB held membership on an entity's board of directors or advisory committees for Sanofi and Janssen; and served on a speakers bureau for Sanofi and Amgen. SAH served as a consultant for BMS/Celgene, Genetech, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, Secura Bio, and Takeda and received research funding from Oncopeptides. CC received honoraria and research funding from Takeda, Janssen, Pfizer, Karyopharm, Oncopeptides, and Bristol Myers Squibb; served as a consultant for Takeda, Celgene, and Janssen; and received research funding from Celgene and Poseida. AJ held membership on an entity's board of directors or advisory committees for Sanofi, Karyopharm, Janssen, GlaxoSmithKline, Amgen, AbbVie, Bristol Myers Squibb, Gracell, and Celgene. TMW served as a consultant for Janssen, Carevive, Seattle Genetics, and Sanofi. TS served as a consultant for Sanofi and Janssen. RZO served as a consultant and received honoraria from Amgen, BioTheryX, Inc., Bristol Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen, Karyopharm, Neoleukin Corporation, Oncopeptides AB, Regeneron, Sanofi-Aventis, and Takeda; received research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda, Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma; holds individual stocks in a privately held company and patents and royalties for Asylia Therapeutics, Inc.; and held membership on an entity's board of directors or advisory committees for Amgen, BioTheryX, Inc., Bristol Myers Squibb, Celg, (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p < 0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p < 0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p < 0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms., (© 2021 Wiley Periodicals LLC.)

Background: For patients with multiple myeloma (MM), each additional line of therapy (LOT) is associated with lower response rates, shorter treatment duration and treatment-free intervals, and increased rates of toxicities and comorbidities. Here, we examine frontline treatment patterns, and attrition rates by LOT among newly diagnosed MM (NDMM) patients in the United States who were eligible or ineligible for autologous stem cell transplant (ASCT)., Methods: Data were identified from three US patient-level databases collectively covering the period January 2000 to September 2018. Patients had an index diagnosis of MM on or after January 1, 2007, medical and prescription insurance coverage at diagnosis, a 1-year look-back period prior to the index diagnosis, no prior malignancies in the 1-year period before index diagnosis, and had received ≥1 LOT., Results: Among patients who did not receive ASCT (non-transplant; n = 22,062), 12,557 (57%) received only 1 LOT and 9505 (43%) received > 1 LOT. Patients receiving only 1 LOT were significantly older, had higher mean Charlson Comorbidity Index (CCI) scores, and higher incidences of comorbidities. Among the 2763 patients receiving ASCT, 2184 received > 1 LOT, and 579 (21%) received only 1 LOT (ie, ASCT was the last treatment). 1682 (61%) patients received induction therapy as frontline treatment, of whom 187 (11%) also received consolidation therapy. The latter group was younger than those who received only induction therapy, had lower mean CCI scores, and comparable or lower incidences of selected comorbidities. The most common frontline therapy for non-transplant and transplant-eligible patients was bortezomib/dexamethasone and bortezomib/lenalidomide/dexamethasone, respectively. Attrition rates across all LOTs were high for non-transplant patients (range, 43-57%) and transplant patients (range, 21-37%). Treatment duration decreased by LOT for non-transplant patients and was consistent across LOTs for transplant patients., Conclusions: In this analysis, a substantial proportion of patients with NDMM who received frontline therapy did not appear to receive a subsequent LOT. These high attrition rates underscore the need to use the most optimal treatment regimens upfront rather than reserving them for later LOTs in which the clinical benefit may decrease.

Multiple myeloma (MM) is a chronically managed blood cancer with a median age of 69 years at the time of diagnosis. Although high dose melphalan and autologous stem cell transplantation (ASCT) remains a standard of care for eligible patients, more than half of the newly diagnosed MM patients are deemed ineligible due to comorbidities or complications of the disease by itself. In this setting, where ASCT is deemed inappropriate, patients could still achieve durable and deep responses if given the appropriate treatment plan. The key concepts of optimizing induction and maintenance strategies while minimizing side-effects are discussed in this review, especially in the context of employing novel agent combinations. It is important to understand the balance between safety and efficacy for each regimen, utilizing maintenance strategy and the best supportive care measures (bone health, infection prevention, and treatment, pain management, etc.). Here, we examine the evidence behind each of those principles and review results from clinical trials for transplant-ineligible (TI) MM.

Systemic light-chain (AL) amyloidosis is a rare hematologic disorder where proteins infiltrate tissues leading to organ failure and death. Cardiac involvement, present in ∼70% of patients, determines stage and prognosis of the disease, with advanced involvement having a median survival of six months. The treatment of light-chain amyloidosis is directed at recovering organ function with therapeutic strategies following those of multiple myeloma with plasma cell-directed therapies. The use of single agent daratumumab has been reported in light-chain amyloidosis achieving rapid and deep responses. The combination of daratumumab, pomalidomide, and dexamethasone (DaraPomD) is particularly interesting for severe AL based on success in multiple myeloma. A 43-year-old female with light-chain amyloidosis and concomitant multiple myeloma presented with severe bowel dysmotility causing abdominal pain, anemia, and a 100-pound unintentional weight loss. A combination of cyclophosphamide, bortezomib, and dexamethasone was initiated but after five cycles her symptoms were progressing and therapy was switched to DaraPomD to optimize response. At the conclusion of two cycles she had achieved an amyloid complete-hematologic response, with her recurring ileus and abdominal pain significantly improved. Additionally, cardiac markers also suggested a rapid response without a common paradoxical worsening of congestive heart failure, and was overall well tolerated. Given the severe symptoms and refractory nature of our patient's disease DaraPomD was reasonable. With the tolerability and response seen, this patient experience supports a formal clinical trial evaluating the safety and efficacy of DaraPomD in light-chain amyloidosis.

Hemorrhagic cystitis (HC) is a common and important complication of allogeneic hematopoietic cell transplantation (HCT). Reactivation of BK virus is its most common cause. The more intense immunosuppressive regimens administered to recipients of grafts from alternative donors have been reported to account for the increased susceptibility to HC in this population. This study compares patients undergoing HCT with either a haploidentical donor or a matched related donor, all of whom received identical immunosuppression with a post-transplantation cyclophosphamide-based regimen. The incidence of HC was significantly higher in the patients receiving a haploidentical graft (P = .01). The higher incidence of HC in haploidentical graft recipients is therefore directly related to the inherent immune deficiency that follows HLA-mismatched transplantation, independent of the intensity of pharmacologic immunosuppression. This finding carries significant clinical impact for the prevention and treatment of HC in haploidentical graft recipients., (Copyright © 2019. Published by Elsevier Inc.)

The revised International Staging System (R-ISS) combines ISS with genetic markers and lactate dehydrogenase and can prognosticate newly diagnosed multiple myeloma (MM). Early relapse (<24 months) after upfront autologous hematopoietic cell transplantation (AHCT) strongly predicts inferior overall survival (OS). We examined the ability of R-ISS in predicting early relapse and its independent prognostic effect on postrelapse survival after an early relapse. Using the Center for International Blood and Marrow Transplant Research database we identified MM patients receiving first AHCT within 18 months after diagnosis with available R-ISS stage at diagnosis (n = 628). Relative risks of relapse/progression, progression-free survival (PFS), and OS were calculated with the R-ISS group as a predictor in multivariate analysis. Among early relapsers, postrelapse survival was tested to identify factors affecting postrelapse OS. The cumulative incidence of early relapse was 23%, 39%, and 50% for R-ISS I, R-ISS II, and R-ISS III, respectively (P < .001). Shorter PFS and OS were seen with higher stage R-ISS. R-ISS was independently predictive for inferior postrelapse OS among early relapsers, as was the presence of ≥3 comorbidities and the use of ≥2 induction chemotherapy lines. R-ISS stage at diagnosis predicts early post-AHCT relapse and independently affects postrelapse survival among early relapsers., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N = 628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication., (Copyright © 2018. Published by Elsevier Inc.)

Importance: The role of high-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) in patients with multiple myeloma continues to be debated in the context of novel agent induction., Objective: To perform a systematic review, conventional meta-analysis, and network meta-analysis of all phase 3 randomized clinical trials (RCTs) evaluating the role of HDT/ASCT., Data Sources: We performed a systematic literature search of Cochrane Central, MEDLINE, and Scopus from January 2000 through April 2017 and relevant annual meeting abstracts from January 2014 to December 2016. The following search terms were used: "myeloma" combined with "autologous," "transplant," "myeloablative," or "stem cell.", Study Selection: Phase 3 RCTs comparing HDT/ASCT with standard-dose therapy (SDT) using novel agents were assessed. Studies comparing single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation and tandem transplantation were included for network meta-analysis., Data Extraction and Synthesis: For the random effects meta-analysis, we used hazard ratios (HRs) and corresponding 95% CIs., Main Outcomes and Measures: The primary outcome was progression-free survival (PFS). Overall survival (OS), complete response, and treatment-related mortality were secondary outcomes., Results: A total of 4 RCTs (2421 patients) for conventional meta-analysis and 5 RCTs (3171 patients) for network meta-analysis were selected. The combined odds for complete response were 1.27 (95% CI, 0.97-1.65; P = .07) with HDT/ASCT when compared with SDT. The combined HR for PFS was 0.55 (95% CI, 0.41-0.74; P < .001) and 0.76 for OS (95% CI, 0.42-1.36; P = .20) in favor of HDT. Meta-regression showed that longer follow-up was associated with superior PFS (HR/mo, 0.98; 95% CI, 0.96-0.99; P = .03) and OS (HR/mo, 0.90; 95% CI, 0.84-0.96; P = .002). For PFS, tandem HDT/ASCT had the most favorable HR (0.49; 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone (HR, 0.53; 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68; 95% CI, 0.53-0.87) compared with SDT. For OS, none of the HDT/ASCT-based approaches had a significant effect on survival. Treatment-related mortality with HDT/ASCT was minimal (<1%)., Conclusions and Relevance: The results of the conventional meta-analysis and network meta-analysis of all the phase 3 RCTs showed that HDT/ASCT was associated with superior PFS with minimal toxic effects compared with SDT. Both tandem HDT/ASCT and single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone were superior to single HDT/ASCT alone and SDT for PFS, but OS was similar across the 4 approaches. Longer follow-up may better delineate any OS benefit; however, is likely to be affected by effective postrelapse therapy.

We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8.5 years. Relapse occurred before 6 months after a second HCT in 46% of the auto/allo patients, compared with 26% of the auto/auto patients. The 6-year postrelapse survival was better in the auto/allo group compared with the auto/auto group (44% versus 35%; P = .05). Mortality due to MM was 69% (n = 101) in the auto/allo group and 83% (n = 229) deaths in auto/auto group. In multivariate analysis, both cohorts had a similar risk of death in the first year after relapse (hazard ratio [HR], .72; P = .12); however, for time points beyond 12 months after relapse, overall survival was superior in the auto/allo cohort (HR for death in auto/auto =1.55; P = .005). Other factors associated with superior survival were enrollment in a clinical trial for HCT, male sex, and use of novel agents at induction before HCT. Our findings shown superior survival afterrelapse in auto/allo HCT recipients compared with auto/auto HCT recipients. This likely reflects a better response to salvage therapy, such as immunomodulatory drugs, potentiated by a donor-derived immunologic milieu. Further augmentation of the post-allo-HCT immune system with new immunotherapies, such as monoclonal antibodies, checkpoint inhibitors, and others, merit investigation., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Race/ethnicity remains an important barrier in clinical care. The authors investigated differences in the receipt of autologous hematopoietic cell transplantation (AHCT) among patients with multiple myeloma (MM) and outcomes based on race/ethnicity in the United States., Methods: The Center for International Blood and Marrow Transplant Research database was used to identify 28,450 patients who underwent AHCT for MM from 2008 through 2014. By using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registries, the incidence of MM was calculated, and a stem cell transplantation utilization rate (STUR) was derived. Post-AHCT outcomes were analyzed among patients ages 18 to 75 years who underwent melphalan-conditioned peripheral cell grafts (N = 24,102)., Results: The STUR increased across all groups from 2008 to 2014. The increase was substantially lower among Hispanics (range, 8.6%-16.9%) and non-Hispanic blacks (range, 12.2%-20.5%) compared with non-Hispanic whites (range, 22.6%-37.8%). There were 18,046 non-Hispanic whites, 4123 non-Hispanic blacks, and 1933 Hispanic patients. The Hispanic group was younger (P < .001). Fewer patients older than 60 years underwent transplantation among Hispanics (39%) and non-Hispanic blacks (42%) compared with non-Hispanic whites (56%). A Karnofsky score <90% and a hematopoietic cell transplantation comorbidity index score >3 were more common in non-Hispanic blacks compared with Hispanic and non-Hispanic whites (P < .001). More Hispanics (57%) versus non-Hispanic blacks (54%) and non-Hispanic whites (52%; P < .001) had stage III disease. More Hispanics (48%) versus non-Hispanic blacks (45%) and non-Hispanic whites (44%) had a very good partial response or better before transplantation (P = .005). Race/ethnicity did not impact post-AHCT outcomes., Conclusions: Although the STUR increased, it remained low and was significantly lower among Hispanics followed by non-Hispanic blacks compared with non-Hispanic whites. Race/ethnicity did not impact transplantation outcomes. Efforts to increase the rates of transplantation for eligible patients who have MM, with an emphasis on groups that underuse transplantation, are warranted. Cancer 2017;123:3141-9. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma. Emerging evidence from phase 3 studies demonstrates that consolidation therapy with HDM/ASCT further improves depth of response and progression-free survival in the context of modern therapy for multiple myeloma. Moreover, unprecedented survival data from ongoing phase 3 studies of patients treated with modern myeloma therapy followed by HDM/ASCT in first-line or second-line therapy reaffirm single and tandem HDM/ASCT as important standards of care for eligible patients. Herein, we review the evolving role of HDM/ASCT for the treatment of patients with newly diagnosed or relapsed multiple myeloma.

This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P < .0001); relapse/progression: 54% versus 20% (P < .0001); progression-free survival (PFS): 41% versus 58% (P < .001), and overall survival (OS): 74% versus 66% (P = .05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P < .0001) and worse PFS (RR, 2.9; P < .0001) beyond 11 months after HCT. In the first 24 months after HCT, auto-HCT was associated with improved OS (RR, .41; P < .0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P = .006). A landmark analysis of patients alive and progression-free at 2 years after HCT confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P < .0001) and inferior PFS (RR, 3.2; P < .0001) and OS (RR, 2.1; P = .04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity-conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Waldenström's macroglobulinemia (WM) is increasingly being associated with amyloidosis particularly of the amyloid light-chain variety. We report on one of the few cases of WM associated with serum amyloid A protein (AA) amyloidosis. Autologous stem cell transplant (ASCT) is now being increasingly used for the treatment of amyloidosis, but most studies are small case series. Traditionally AA amyloid is associated with connective tissue disorders and periodic fever syndromes and has been treated by addressing the underlying condition. We present the first case of serum amyloid A being treated with melphalan-based ASCT to deal with the underlying WM and thereby control the amyloid, thus demonstrating the viability of this novel approach for the treatment of this disorder., (Copyright © 2013 S. Karger AG, Basel.)

The revised International Staging System (R-ISS) combines ISS with genetic markers and lactate dehydrogenase and can prognosticate newly diagnosed multiple myeloma (MM). Early relapse (

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N = 628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.