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High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL). However, the optimal conditioning regimen is unclear. Different conditioning regimens prior to AHCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We sought to compare the two regimens for patients with relapsed NHL undergoing AHCT. We retrospectively compared the outcomes of patients treated with BEAM (N = 269) at The Ohio State University and BUCYVP16 (N = 409) at the Cleveland Clinic followed by AHCT between 2006 and 2014. The primary endpoints were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Patient characteristics between the two groups were similar. After a median follow-up of 3.9 years for BEAM and 4.3 years for BUCYVP16 from AHCT, the rate of relapse (p = 0.69), PFS (p = 0.52), and OS (p = 0.11) were similar between the two conditioning regimens. No differences in survival outcomes were seen in disease subtypes. Multivariable analysis showed significant association toward improved OS with BEAM (HR: 1.56, 95% CI 1.16-2.10) (p < 0.01). Even though the study is limited by its retrospective nature and some differences in cohort, the findings indicate that BEAM could serve as an alternative conditioning regimen prior to AHCT for NHL.

Chronic graft-versus-host-disease (cGVHD) is one of the primary causes of morbidity and mortality for patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HCT). In recent years, advancements in allo-HCT have allowed a broader range of patients to receive transplant, particularly older patients. We sought to assess the impact of cGVHD on outcomes in patients undergoing allo-HCT, for older patients as compared to their counterparts. We performed a retrospective analysis of all patients who underwent allo-HCT 1999–2018. Our results showed that those patients who developed cGVHD by D + 180 had an increased risk and incidence of NRM as compared to those patients without cGVHD. There was no significant difference in outcomes for those patients with cGVHD by age (≥60 years old [yo] and <60 yo). These findings suggest the significant morbidity of cGVHD, regardless of age. [ABSTRACT FROM AUTHOR]

The standard preparative regimen for autologous stem cell transplant (ASCT) in multiple myeloma (MM) is 200 mg/m2 of intravenous melphalan; however, a dose of 140 mg/m2 is often used when concerns exist related to patient age, performance status, organ function, and other factors. It is unclear whether a lower dose of melphalan impacts post-transplant survival outcomes. We performed a retrospective review of 930 patients with MM who underwent ASCT with 200 mg/m2 versus 140 mg/m2 melphalan. On univariable analysis, no difference in progression-free survival (PFS) was observed, however, an overall survival (OS) benefit was observed in patients receiving 200 mg/m2 melphalan (p = 0.04). Multivariable analyses showed patients receiving 140 mg/m2 faired no worse than those receiving 200 mg/m2. While a subset of younger patients with normal renal function may achieve superior OS with a standard dose of 200 mg/m2 melphalan, these findings suggest an opportunity to individualize the ASCT preparative regimen to optimize outcomes. [ABSTRACT FROM AUTHOR]

Summary: Patients with multiple myeloma are at increased risk of vascular thromboembolic events (VTEs). This post hoc analysis evaluated VTEs in the randomised phase 2 GRIFFIN study (ClinicalTrials.gov Identifier: NCT02874742) that investigated lenalidomide/bortezomib/dexamethasone (RVd) ± daratumumab (D). Patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation (ASCT) received D‐RVd/RVd induction, high‐dose therapy and ASCT, D‐RVd/RVd consolidation and up to 2 years of lenalidomide maintenance therapy ± D. VTE prophylaxis was recommended (at least aspirin, ≥162 mg daily) in accordance with International Myeloma Working Group guidelines. In the safety population (D‐RVd, n = 99; RVd, n = 102), VTEs occurred in 10.1% of D‐RVd patients and 15.7% of RVd patients; grade 2–4 VTEs occurred in 9.1% and 14.7%, respectively. Median time to the first onset of VTE was longer for D‐RVd versus RVd patients (305 days vs 119 days). Anti‐thrombosis prophylaxis use was similar between arms (D‐RVd, 84.8% vs RVd, 83.3%); among patients with VTEs, prophylaxis use at time of first VTE onset was 60.0% for D‐RVd and 68.8% for RVd. In summary, the addition of daratumumab to RVd did not increase the incidence of VTEs, but the cumulative VTE incidence was relatively high in this cohort and anti‐thrombotic prophylaxis use was suboptimal. [ABSTRACT FROM AUTHOR]

Maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM) is the standard treatment and recommended to be continued until disease progression. However, in the real world, patients discontinue treatment due to various reasons. We sought to determine the effect of early versus late discontinuation on survival outcomes in MM patients who underwent ASCT at The Ohio State University. We retrospectively reviewed 340 patients who underwent ASCT from 2005 to 2016 and received maintenance therapy for at least six months without progression. We compared the outcomes of patients who received maintenance for three years or less (early group) to the patients who continued maintenance beyond three years (late group). Lenalidomide (89%) and bortezomib (10%) were the most common agents used for maintenance chemotherapy. In Kaplan–Meier analysis, patients in the late group had prolonged progression-free (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). The 5-year estimated OS in late group was 96% vs. 79% in the early group and 5-year PFS was 80% in late group vs. 50% in the early group. The most common reasons for discontinuation of maintenance in early group were adverse events (55.9%) and patient preference (22.5%). For the late group, it was disease progression (23.9%) and adverse events (14.3%). Fifty-five percent of patients in the late group were still on maintenance treatment at the last follow-up. Continuation of maintenance therapy was thus associated with improved outcomes, while adverse events prevented most patients from continuing treatment. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT. Methods: We performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS). Results: Of the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence. Conclusion: Our study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 49 years. Median time to tocilizumab administration was 9 days (range, 3–16). Six patients had complete responses (40%) with a resolution of aGVHD. From the last contact, median overall survival for responders was not yet reached vs. 31 days for non-responders (p =.0002). Patients with skin and/or GI aGVHD demonstrated the greatest benefit. Patients with liver aGVHD did not respond. Future studies are needed to evaluate tocilizumab prior to steroid failure. [ABSTRACT FROM AUTHOR]

Statins possess potent immunomodulatory effects that may play a role in preventing acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). We performed a phase II study of atorvastatin for aGVHD prophylaxis when given to allo-HCT recipients and their HLA-matched sibling donors. Atorvastatin (40 mg/day) was administered to sibling donors, beginning 14 days before the anticipated start of stem cell collection. Allo-HCT recipients (n = 40) received atorvastatin (40 mg/day) in addition to standard aGVHD prophylaxis. The primary endpoint was cumulative incidence of grades II to IV aGVHD at day 100. Atorvastatin was well tolerated, with no attributable grades III to IV toxicities in donors or their recipients. Day 100 and 180 cumulative incidences of grades II to IV aGVHD were 30% (95% confidence interval [CI], 17% to 45%) and 40% (95% CI, 25% to 55%), respectively. One-year cumulative incidence of chronic GVHD was 43% (95% CI, 32% to 69%). One-year nonrelapse mortality and relapse incidences were 5.5% (95% CI, .9% to 16.5%) and 38% (95% CI, 18% to 47%), respectively. One-year progression-free and overall survival rates were 54% (95% CI, 38% to 71%) and 82% (95% CI, 69% to 94%). One-year GVHD-free, relapse-free survival was 27% (95% CI, 16% to 47%). These results did not differ from our historical control subjects (n = 96). Although safe and tolerable, the addition of atorvastatin did not appear to provide any benefit to standard GVHD prophylaxis alone. [ABSTRACT FROM AUTHOR]

Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m2 intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25-2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921). [ABSTRACT FROM AUTHOR]

Autologous stem cell transplant (ASCT) is an effective treatment for multiple myeloma (MM). However, the timing of ASCT in the era of novel agents (lenalidomide, thalidomide, bortezomib) is unknown. We retrospectively reviewed the outcome of patients with MM who received novel agent-based induction treatment and received first ASCT within 12 months of diagnosis (early ASCT, n = 102) or at a later date (late ASCT, n = 65). Median time to ASCT was 7.9 months vs. 17.7 months in early vs. late ASCT. The 3- and 5-year overall survival (OS) from diagnosis was 90 and 63% vs. 82 and 63% in early and late ASCT, respectively ( p = 0.45). Forty-one and 36 patients in the early and late ASCT groups have relapsed or progressed, with median time to relapse of 28 and 23 months ( p = 0.055). On multivariable analysis, factors predictive of increased risk for progression were International Scoring System (ISS) stage III ( p = 0.007), and less than a very good partial response (< VGPR) post-ASCT ( p < 0.001). A factor predictive of worst outcome for OS was being on hemodialysis ( p = 0.037). No superiority of one agent was seen. In summary, early or late ASCT is a viable option for patients with MM receiving induction treatment with novel targeted therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this review is to provide an overview of the current scientific evidence concerning the role of stem cell transplantation in multiple myeloma. During the past decade, several new treatment options have become available, thereby questioning the role of stem cell transplantation for the management of multiple myeloma. This review focuses on these studies, demonstrating a benefit for autologous stem cell transplantation (auto-SCT). We also reviewed maintenance post auto-SCT and utility of allogeneic stem cell transplant. Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs. Tandem auto-SCT followed by maintenance has shown a progression-free survival (PFS) benefit in high-risk MM, and hence can be considered in young and fit patients with high-risk disease. Auto-SCT has the advantages of resetting the bone marrow microenvironment, short-lived toxicity compared to the long-term physical and financial toxicities of continued chemotherapy in the absence of SCT, very low transplant-related mortality (TRM) in high volume centers, and providing longer disease-free survival when followed by maintenance therapy. Allogeneic SCT is one potentially curative option for MM, albeit with an increased risk of death due to high TRM. Strategies to modulate the graft-versus-host disease (GVHD) while maintaining or improving the graft-versus-myeloma (GVM) effect could place allogeneic SCT back in the treatment armamentarium of MM. [ABSTRACT FROM AUTHOR]

The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma, and AL amyloidosis) that were presented in the 2020 American Society of Clinical Oncology virtual scientific symposium are summarized here. Data from large phase-3 studies (CASSIOPEIA, ENDURANCE, and TOURMALINE-MM4 trials) and phase-2 studies (SWOG 1211, GMMG CONCEPT trials) for newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation are described. Updates from previous important studies for multiple myeloma (STaMINA) along with studies on three different chimeric antigen receptor (CAR-) T cell products are also described. Results of clinical studies involving the use of anti-myeloma drugs with novel mechanisms of action such as immunoconjugates, selinexor, venetoclax, monoclonal antibodies, and data on minimal residual disease (MRD) are discussed. These data provide an overview of the efficacy and safety of the various treatments in multiple myeloma and could lead to changes in our clinical practice, which could pave the path for a "cure" in myeloma. [ABSTRACT FROM AUTHOR]

Prophylaxis with fluoroquinolone (FQ) for patients undergoing autologous stem cell transplantation (ASCT) remains controversial. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. In accordance with institutional policy, patients undergoing ASCT for multiple myeloma routinely receive levofloxacin prophylaxis during their period of neutropenia, whereas patients undergoing the ASCT for lymphoma do not. We retrospectively examined patients with multiple myeloma (MM) or lymphoma undergoing ASCT between July 2015 and July 2018 for evidence of positive blood cultures. A total of 172 patients underwent ASCT for lymphoma and 343 underwent ASCT for MM. The 2 cohorts were similar in terms of baseline characteristics. Almost 20% (35 of 172) of the patients with lymphoma and 5.2% (18 of 342) of those with MM had a bloodstream infection (BSI). BSI occurred an average of 2 days earlier in patients with lymphoma compared with patients with MM (day +5 versus day +7; P =.0003). The 2 cohorts recovered absolute neutrophil count at the same time. Hospital length of stay was 2 days shorter for patients with MM (median, 20 days versus 18 days; P =.01). The majority of the organisms were gram-negative in both cohorts. Of the organisms commonly tested for FQ sensitivity, only 1 of 25 was resistant in the lymphoma cohort, compared with 7 of 9 in the MM cohort (P <.0001), with 4 being multidrug resistant. The odds of developing a BSI were 4.6 times greater in the lymphoma cohort compared with the MM cohort (95% confidence interval [CI], 2.52 to 8.40; P <.0001). In total, 23 of 172 patients with lymphoma (13.4%) and 28 of 342 patients with MM (8.2%) developed Clostridium difficile infection (odds ratio, 1.73; 95% CI,.96 to 3.11; P =.066). Two infection-related deaths occurred in the MM cohort. Our data indicate that FQ prophylaxis reduces the risk of BSI in patients undergoing ASCT but increases the incidence of resistant organisms. We recommend routine antimicrobial prophylaxis in patients undergoing ASCT to reduce the risk of BSI, along with a systematic and regular review of outcomes. [ABSTRACT FROM AUTHOR]

• The combination of vorinostat and lenalidomide as maintenance post-transplantation is tolerable and induces durable response. • With a median follow-up of 89.8 months from autologous stem cell transplantation, the median progression-free survival was 64.3 months (range, 21.7 months to not reached [NR]) and overall survival was not reached (range, 53.0 months to NR). • The use of lenalidomide plus vorinostat could prove to be a promising maintenance strategy in patients with newly diagnosed multiple myeloma. Post-autologous stem cell transplantation (ASCT) maintenance therapy with lenalidomide is standard of care for patients with multiple myeloma (MM). Effective and tolerable drug combinations may further enhance the clinical response post-ASCT. Vorinostat, a histone deacetylase inhibitor, induces antiproliferative and proapoptotic effects in patients with MM. We hypothesized that combination maintenance therapy would further prolong the clinical response achieved from transplantation. We previously reported that the combination of lenalidomide and vorinostat as maintenance post-ASCT was tolerable in 16 patients with MM. We now present the long-term follow up of these patients. Progression-free survival (PFS) and overall survival (OS) outcomes were characterized using the Kaplan-Meier method. Five patients (31%) had high-risk disease, and the median number of lines of therapy before ASCT was 1 (range, 1 to 5). With a median follow-up of 89.8 months from ASCT, the median PFS was 64.3 months (range, 21.7 months to not reached [NR]), and OS was not reached (median, 53.0 months to NR). At the time of this report, 5 patients remained on the study. The combination of vorinostat and lenalidomide as maintenance post-ASCT is tolerable and induces a durable response. A phase III randomized study of lenalidomide versus a combination with vorinostat is warranted. [ABSTRACT FROM AUTHOR]

• Autologous stem cell transplant (ASCT) induces global transcriptional T cell changes and altered molecular levels of markers of T cell subtypes, T cell activation, and exhaustion in patients with multiple myeloma. • High LAG3 transcript expression in T cells detectable as early as 3 months post-transplant is associated with inferior clinical outcomes in patients with myeloma. • ASCT affected soluble levels of molecules with immunomodulatory function by increasing plasma HVEM and TIM3. • ASCT promotes an exhausted immunophenotype in CD4+ cells and a senescent/anergic immunophenotype in CD8+ subsets. • Future work targeting immune defects in multiple myeloma is warranted to augment or restore T cell responses using the next generation of immune checkpoint inhibitors. Autologous stem cell transplant (ASCT) is the standard of care for patients with multiple myeloma (MM). The clinical significance of peripheral blood T lymphocyte (PBTL) immunologic changes associated with ASCT is poorly understood. Here we evaluated T cell transcriptional messenger RNA profiles and immunophenotypes to correlate immunologic senescence, exhaustion, and anergy with clinical endpoints in a cohort of patients with MM undergoing ASCT. ASCT induced global transcriptional T cell changes and altered molecular levels of markers of T cell subtypes, T cell activation, and exhaustion. These included reduced CD4/CD8 ratio, skewing toward the Th1 subset, reduced expression of costimulatory receptors CD27 and CD28, heightened T cell activation, and increased expression of immune modulatory molecules LAG3 and PD1. Multicolor flow cytometry experiments confirmed altered circulating CD4 and CD8 subsets and skewing toward differentiated effector cells. Moreover, ASCT promoted an exhausted immunophenotype in CD3+CD4+ subsets and a senescent immunophenotype in CD3+CD8+ subsets. Subset-specific altered expression was also seen for surface molecules with immunomodulatory function. ASCT affected soluble levels of molecules with immunomodulatory function by increasing plasma HVEM and TIM3. High molecular LAG3 level was associated with inferior event-free survival post-ASCT (hazard ratio = 5.44; confidence interval, 1.92 to 15.46; P =.001; adjusted P [controlling for false discovery rate] =.038). Using a comprehensive evaluation of PBTLs on a molecular and phenotypic level, we have identified that ASCT induces global T cell alterations with CD4 and CD8 subset-specific changes. Moreover, LAG3 emerged as an early biomarker of adverse events post-ASCT. These findings will support the development of treatment strategies targeting immune defects in MM to augment or restore T cell responses. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host disease (aGVHD) continues to be a frequent and devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT), posing as a significant barrier against the widespread use of HSCTs as a curative modality. Recent studies suggested serum/plasma microRNAs (miRs) may predict aGVHD onset. However, little is known about the functional role of circulating miRs in aGVHD. In this article, we show in two independent cohorts that miR-29a expression is significantly upregulated in the serum of allogeneic HSCT patients at aGVHD onset compared with non-aGVHD patients. Serum miR-29a is also elevated as early as 2 wk before time of diagnosis of aGVHD compared with time-matched control subjects. We demonstrate novel functional significance of serum miR-29a by showing that miR-29a binds and activates dendritic cells via TLR7 and TLR8, resulting in the activation of the NF-κB pathway and secretion of proinflammatory cytokines TNF-α and IL-6. Treatment with locked nucleic acid anti-miR-29a significantly improved survival in a mouse model of aGVHD while retaining graft-versus-leukemia effects, unveiling a novel therapeutic target in aGVHD treatment or prevention. [ABSTRACT FROM AUTHOR]

Nonrelapse mortality (NRM) after reduced-intensity allogeneic transplants is likely to be influenced by abnormalities in renal function. We studied 141 patients diagnosed with acute myelogenous leukemia (AML) (n = 131) or high-risk myelodysplastic syndrome (MDS) (n = 10) who underwent allogeneic transplantation with fludarabine (Flu)/melphalan (Mel)-based regimens and hypothesized that moderate to mild renal function impairment increases NRM in this setting. Flu dose consisted of 25-30 mg/m2 for 4 days and Mel dose was 100-180 mg/m2. Donors were HLA-compatible siblings (n = 69) and matched unrelated donors (n = 72). Disease status at transplantation was complete remission (n = 56, 40%) or active disease (n = 85, 60%). The influence of the estimated glomerular filtration rate (GFR) measured before transplantation on outcomes was analyzed. GFR was estimated by both the Cockcroft-Gault (CG) and the modified diet in renal disease (MDRD) equations, using the creatinine value obtained prior to starting chemotherapy. Evaluated outcomes were overall survival (OS), NRM, and treatment-related mortality (TRM) at day 100 and 1-year posttransplantation. Median age was 55 years (range: 21-74 years); 59% of the patients were male. Estimated GFR by CG was ≥90 for 45 (32%), 60-89 for 78 (55%), and <60 for 18 (13%) patients. When estimated by MDRD, GFR was ≥90 for 65 (46%), 60-89 from 66 (47%), and <60 for 10 (7%) patients. The majority of patients by both estimations had a GFR between 60 and 89 (n = 78 by CG and n = 66 by MDRD) with no difference in the evaluated outcomes between this group and the subgroup of patients with a GFR <60 (P > .05). There were no differences in OS and NRM at day 100 and 1-year posttransplantation in the 3 groups by any GFR estimation method. In conclusion, a mild to moderate decrease in GFR was not associated with an increase in NRM. [Copyright &y& Elsevier]

MM is a clonal disorder of malignant plasma cells. Standard of care for newly diagnosed MM is induction with triplet regimen chemotherapy followed by ASCT. Patients are stratified based on cytogenetic analysis as being high risk and standard risk. t(11;14) comprises ∼ 15-20% of newly diagnosed MM, making it the most common translocation. t(11;14) has been classified as standard risk. However, it is now increasingly being considered as intermediate risk, conferring inferior outcome compared with standard-risk MM.(Walker, Wardell et al. 2012) We performed a retrospective analysis of 806 pts with newly diagnosed MM who underwent ASCT at our institution. Pts were stratified as high risk in the presence of t(4;14), t(14;16), gain 1q or del17p.by FISH. PFS and OS rates were estimated using Kaplan-Meier method. Log-rank tests were used to compare the PFS and OS between the two groups. The Cox proportional hazard models were used to estimate the hazard ratios (HR). Among 806 patients, 156 pts (19.4%) were positive for t(11;14). 81.5% of pts were 65 yrs or younger, and 59% were males. There were no significant differences in pt characteristics (see table) Median PFS from ASCT in pts with t(11;14) was 3.0 yrs (95% CI: 2.3-4.3) vs. 3.3 yrs (95% CI: 2.8-3.8) in those without t(11;14)[HR=1.03, 95% CI: 0.82-1.29, p=0.81. There was no statistical difference in OS from ASCT [HR of 0.97 (95% CI: 0.70-1.33, p 0.84)]. 5 yr PFS rate was 37% for pts with t(11;14) & 53% in pts without. 5 yr OS rate was 65% for pts with t(11;14) & 66% for those without. t(11;14) is a common cytogenetic abnormality in MM. According to our analysis, there is no significant difference in outcomes following ASCT in both high risk and standard risk subgroups. t(11;14) MM is predicted to be BCL-2 dependent and the use of BCL-2 inhibitors in induction or post-ASCT maintenance is an attractive option to improve outcomes. [ABSTRACT FROM AUTHOR]

MM is the 2nd most common hematological malignancy in the USA. The treatment landscape has drastically evolved over the last few years. While clinical trials have been pivotal in this endeavor, the under-representation of racial/ethnic minorities has been a constant issue. Population studies (Smith, Ambs et al. 2018) have demonstrated poorer outcomes in non-white (pts) across many malignancies including MM. We performed a retrospective analysis of 806 pts with newly diagnosed MM who underwent ASCT at our institution. Pts were stratified as high risk in the presence of t(4;14), t(14;16), gain 1q or del17p. Correlation with PFS and OS was conducted by univariable and multivariable analyses. Log-rank test was used to compare PFS and OS. 16% of pts were non-white. High risk comprise 30.4% of total pts with 23.2% non-white. PFS was similar in both non-white and white pts with a HR=1.02 (0.82-1.28; p=0.86). There was no statistically significant different in OS from time of transplant (HR=1.09 (0.81-1.47) p value = 0.57)). Upon further stratification by standard risk v/s high risk, outcomes in non-whites and whites remain similar (HR=1.05 (0.64-1.71; p value 0.86) for PFS and HR=1.06 (0.55-2.05), p=0.86 for OS) Inferior outcomes in racial minorities is a concern in all malignancies, including MM despite advances in therapeutics. Under-representation in clinical trials and lack of access to care have been touted as potential causes. Our experience suggests that non-white pts do as well as white pts if they have equal access to treatment, and this is seen even in patients with high risk cytogenetics. There is a compelling need to identify obstacles to appropriate care for these minorities and further bridge these gaps in outcomes. Further efforts are also needed to evaluate genomic differences in different ethnicities to further personalize induction/maintenance regimens. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic AL amyloidosis (AL). However, the decision to utilize maintenance therapy following ASCT remains controversial and largely unexplored. Furthermore, the growing relevance of cytogenetics in AL may help dictate this maintenance decision as well. It is also relevant to note the emergence of novel targeted therapy options for AL patients, including the plasma cell monoclonal antibody daratumumab, that offer an exciting option in combination therapies with ASCT. As such, the present study aims to a) determine the prognostic significance of utilizing maintenance therapy following ASCT b) assess the potential impact of cytogenetics on this decision, and c) present novel data on the survival benefits of daratumumab-treated patients who have undergone ASCT. A retrospective chart review was performed on 50 consecutive AL patients who underwent ASCT at The Ohio State University. Patients received high dose Melphalan (140 or 200 mg/m2) prior to ASCT. Patients were divided into subgroups based on FISH, and whether or not they had received maintenance therapy following transplant. Primary endpoints were progression free survival (PFS) and overall survival (OS), both estimated via the Kaplan-Meier survival function. The log-rank test was used to test the equality of survivor functions between different groups of patients. Twenty-eight patients (56%) received maintenance and 22 (44%) did not. There was no difference in age, dose of melphalan used, disease stage and number of organs involved between the two groups. There was no statistically significant difference in OS (p=0.32) and PFS (p=0.66) between patients who received maintenance versus those patients who did not receive maintenance (Figure 1A). Among patients with abnormal FISH, there was no difference in survival between the two groups (OS-p=0.65; PFS-p=0.15) (Figure 1B). Patients with three or more organs with AL involvement had worse OS/PFS versus those with 2 or less (OS-p=0.001; PFS-p=0.015). However, among these patients with 2 or more organs involved, the decision to utilize maintenance vs not showed no difference in PFS/OS. Lastly, further evaluation of a subset of patients treated with daratumumab showed no difference in outcome whether or not they underwent ASCT or consolidation. In this small retrospective analysis, maintenance therapy post ASCT had no impact on the PFS or OS of patients with AL, even when further stratified based on degree of organ involvement. Survival was also not affected by cytogenetic abnormalities or with addition of novel monoclonal-targeted therapies. It is clear that a larger prospective study is needed to assess the benefit of maintenance post ASCT in AL amyloid patients. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression free survival (PFS) and overall survival (OS). The Ohio State University began utilizing ASCT for newly diagnosed MM (NDMM) patients in 1992. With the introduction of new, more effective drugs used before and after ASCT over time, we performed retrospective survival analysis in NDMM patients receiving ASCT from 1992-2016. Consecutive 1002 NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for treatment of MM: 1992-1998-group 1, 1999-2002-group 2, 2003-2008-group 3, 2009-2013-group 4, and 2014-2016-group 5. Pre-ASCT conditioning regimen was melphalan, 140 or 200 mg/m2. High-risk patients had del17, t(4:14), t(14:16), and/or 1q abnormality. Primary endpoints were PFS and OS. Kaplan Meier curves were used to calculate PFS and OS. Across the years (1992-2016), there was a statistically significant improvement in both PFS (p<0.01) and OS (p<0.01). Median PFS and OS from date of transplantation was 1.3 and 2.0 years in group 1; 1.0 and 3.2 years in group 2; and 2.0 and 5.8 years in group 3 respectively. This response was further improved to PFS and OS of 4.1 years and not reached (NR) in group 4, and 3.8 years and NR in group 5 respectively (Figure 1). The 3 year PFS of groups 1 through 5 was 26%, 25%, 35%, 57% and 58%, respectively, and the 3 year OS was 45%, 54%, 74%, 82% and 80%, respectively. On subset analysis, across years, significant increases in PFS (p<0.01) and OS (p<0.01) were seen in patients ≤65 years of age. For patients >65 years old, there was a statistically significant improvement in PFS (p<0.01) but not in OS (p=0.054). For both standard and high-risk disease, there was significant improvement in PFS (p=0.01 and p=0.01), and OS (p=0.02 and p<0.01), respectively. From time of diagnosis, both PFS (p < 0.001) and OS (p < 0.001) were significant across the years. The rate of response both pre- and post-transplant showed statistically significant improvement across the years (p<0.01). The pre-transplant rate of very good partial response (VGPR), or better, increased from 5.3% in group 1 to 54% in group 5. The post-transplant rate of response (VGPR or better) also increased from 31.5% in group 1 to 76.3% in group 5. Survival since 1992 have improved primarily due to inclusion of novel therapies and maintenance. For NDMM patients receiving ASCT, the 3 year overall survival rate has significantly improved from 45% in 1992-1998 to 80% in 2014-2016, which is similar to the post-ASCT OS shown in the 2012 study by McCarthy et al. The significantly increasing age of NDMM patients receiving ASCT over time suggests improvement in supportive care and tolerability of current therapies. [ABSTRACT FROM AUTHOR]

A meta-analysis of three large randomized trials has demonstrated that len maint prolongs progression free survival (PFS) and overall survival (OS) in pts with MM who have undergone ASCT. While len maint benefits pts with both high-risk and standard-risk cytogenetics, it does not appear to provide equal magnitude of benefit to patients with high-risk cytogenetics. We conducted a retrospective analysis comparing the outcomes of pts with MM who underwent ASCT at our institution and len maint compared to no maint. We further evaluated the impact of len maint on the two cytogenetic groups. We performed a retrospective analysis of 1002 consecutive pts with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received including maint, and clinical outcomes. Pts were excluded from the analysis if they received len combination or other drug maint therapies. High-risk cytogenetics was defined as having t(4;14), t(14;16), gain 1q, or del17p. PFS and OS were estimated using Kaplan-Meier method. Log-rank test was used to compare PFS and OS between the groups and Cox proportional hazard models were used to estimate the hazard ratios (HR). Pt characteristics are listed in Table 1. 484 pts (53.3%) received no maint while 423 pts (46.7%) received len maint. 245 pts (24.4%) had high-risk cytogenetics while 561 pts (56%) had standard-risk cytogenetics with the remaining unknown. Both PFS and OS were significantly better in the len maint group compared to the no maint group (Figure 1). Adjusting for pts age at transplant, cytogenetic risk, pre-transplant and post-transplant disease status, and ISS staging, the superiority in PFS and OS remained statistically significant, HR=0.50 (95% CI: 0.41-0.62), p<0.001 for PFS, HR=0.48 (95% CI: 0.36-0.63), p<0.001 for OS, respectively. Furthermore, both high-risk and standard-risk groups derived benefit from len maint (p<0.001, Figure 2). Consistent with previously published data, our results demonstrate an improvement in outcomes in MM pts treated with len maint following ASCT compared to no maint regardless of cytogenetic risk group. Larger studies are needed to assess the individual benefit obtained with len maint with each high-risk cytogenetic abnormality. Several trials incorporating newer drugs with novel mechanisms of action are currently being done that could further optimize maint therapy and lead to better outcomes in high-risk group. [ABSTRACT FROM AUTHOR]

High dose chemotherapy followed by ASCT is the standard of care in the treatment of eligible patients with MM. Melphalan has been the drug of choice for conditioning therapy at a dose of 200 mg/m2 (mel 200). However, for elderly patients (older than 65 years) and renal dysfunction (serum creatinine>2), a reduced dose of 140 mg/m2 (mel 140) is commonly used based on a prior retrospective study. We conducted a retrospective analysis comparing the outcomes of patients with MM who underwent ASCT at our institution at the standard dose of melphalan versus reduced dose. 1) Compare efficacy of melphalan 200mg/m2 versus 140mg/m2 for ASCT in MM. 2) Assess impact of age and renal dysfunction on the outcome in MM. 3) Compare the clinical characteristics of patients who underwent ASCT. We performed a retrospective analysis of 1002 consecutive patients with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received, dose of melphalan conditioning and clinical outcomes. Progression-free survival (PFS) was defined from time of transplantation to disease progression or death, censoring those alive without progression at the last contact. Overall survival (OS) was calculated from the time of transplantation to death, censoring those alive at last contact. PFS and OS were estimated using Kaplan-Meier method. Log-rank tests were used to compare PFS and OS between the groups, and Cox proportional hazard models were used to estimate the hazard ratios (HR). 946 patients received high dose melphalan conditioning prior to ASCT, of which 807 patients received mel 200 while 126 patients received mel 140. Thirteen patients were excluded due to alternate dosing. Around 16% of patients in the mel 200 group were older than 65 years compared to 42.1% in the mel 140 group. More patients in the mel 140 group had ISS stage 3 MM compared to mel 200 (64.7% vs 24.6%). Renal dysfunction was seen in 69.8% of patients in the mel 140 group while 15.5% had it in the mel 200 group. PFS of patients who received mel 140 was not inferior to those who received mel 200 (p=0.29, figure 1). Overall survival of patients who received mel 200 was better than those who got mel 140 by univariate analysis (p=0.048, figure 1). However, after adjusting for age, ISS staging and renal dysfunction, the difference in OS was not significant. Patients who got mel 140 did no worse than those who received mel 200 in terms of disease outcome as assessed by PFS and OS. [ABSTRACT FROM AUTHOR]

Introduction Autologous stem cell transplant patients (ASCT) are at risk for bacterial. Antibacterial prophylactic strategy is variable among centers. Fluoroquinolone prophylaxis in ASCT patients has not been found to add a survival benefit. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. Methods At our institution, patients undergoing ASCT for multiple myeloma (MM) receive levofloxacin 500 mg daily as prophylaxis, while lymphoma patients do not. We retrospectively examined MM or lymphoma patients undergoing ASCT between July of 2015 and 2018 for bacteremia episodes. MM patients received melphalan and lymphoma patients received BEAM. All patients received growth factor support. Clinical and microbial data was recorded and analyzed using SPSS. Results In total, 172 patients underwent ASCT for lymphoma and 343 for MM. Seventeen percent (30/172) of lymphoma patients and 5.5% (19/324) of MM patients had febrile neutropenic episodes associated with bacteremia. Relative risk was 3.1 [1.83 – 5.43, p < 0.001]. Median time to positive blood cultures was 5 [0 – 9] days for lymphoma patients and 7 [4 – 9] days for MM patients. All but two patients had a median absolute neutrophil count (ANC) of zero at the time of bacteremia. There were no resistant organisms in the lymphoma group while 37% (7/19) of the infections in the MM group were resistant to levofloxacin among other drugs, including 4 extended-spectrum beta-lactam (ESBL) E. coli isolates. The incidence of CDI was 13.4% in the lymphoma group and 8.2% in the MM group with p=0.06. Patients with resistant isolates required longer time to clear blood cultures. Two infection-related deaths occurred in the MM group, one from CDI colitis and one from Vancomycin-resistant Enterococcus bacteremia (Table 1). Discussion Fluoroquinolone prophylaxis resulted in less blood stream infection episodes but more breakthrough infections with resistant isolates. There was no statistically significant difference between the rates of CDI infections despite a trend to lower incidence in the prophylaxis group. Bacteremia was more difficult to treat for the resistant isolates. There were two infection-related mortalities in the prophylaxis group. In the era of antimicrobial resistance, further reevaluation of the utility of fluoroquinolone prophylaxis should be carefully weighed against the risks. [ABSTRACT FROM AUTHOR]